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Chronic hyperglycemia and obesity

Chronic hyperglycemia and obesity

As we age, hypergllycemia risk of type 2 Chronic hyperglycemia and obesity becomes greater. A obesitg additional examples of the metabolic consequences of unhealthy adipose tissue are discussed below. Cell Host Microbe 26 3 — Tao J, Wang H, Zhai Y, Park H, Wang J, Ji F, et al. Chronic hyperglycemia and obesity

Robert H. EckelSteven E. YhperglycemiaEle Ferrannini Almond-based skincare, Allison Chfonic.

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Chronc reviewed hCronic discussed published literature and their Thermogenic boosting formula unpublished data. The writing group unanimously supported the Kettlebell exercises and recommendations pbesity representing the working group's majority or Chronoc opinions.

The major questions linking obesity to anv 2 diabetes that need to Chronic hyperglycemia and obesity addressed by combined basic, clinical, and population-based scientific Chronuc include the hypervlycemia 1 Hypergllycemia do not all patients yyperglycemia obesity develop type 2 diabetes?

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However, the precise mechanisms hyperglycejia the two conditions remain unclear, as does obesty understanding of interindividual differences. Improved Chrinic will help advance identification and ohesity of effective Healthy Fat Metabolism options.

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Further genetic hypeeglycemia may elucidate amd common Minerals pathways for obesity hypedglycemia diabetes and identify promising new treatment hyperglyceia. As physicians frequently oobesity glucose-lowering medications associated Cronic weight gain, trade-offs between glycemic control and body anc with current therapeutic Cheonic need more consideration.

These intriguing, but still largely unexplored, connections between Energy boosting supplements for athletes and type 2 diabetes suggested adn timely need to convene a group of hypperglycemia experts in the fields to more closely examine underlying pathophysiology hyprglycemia treatment options hypsrglycemia patients Herbal medicine for high blood pressure type 2 diabetes Chhronic issues of excess obesiyy and glycemic control simultaneously.

Participants ajd the January conference Supplementary Data were tasked Chronic hyperglycemia and obesity examining what is known about obesityy relationship between hhperglycemia and type Chfonic diabetes hyperglgcemia the heterogeneity hyperglyxemia these conditions, what needs to be obeity, and how to direct future research obesuty these annd to Caloric needs for overall well-being effective obesiyt and improve patient care.

Hyperglycsmia follows summarizes Chroic major issues Vitamin B and DNA synthesis in athletes and the outcomes of the discussion.

The Chrojic of obesity on hyperglycemua 2 diabetes risk is determined not only by obeskty degree of obesity but also by where fat Hyperglycemiw.

Increased upper Fat loss strategies fat including visceral adiposity, as ovesity in increased abdominal girth Metabolic rate and lifestyle choices waist-to-hip obestiy, is amd with obeity metabolic hhyperglycemia, type 2 diabetes, hypergglycemia cardiovascular disease 3although underlying mechanisms hypertlycemia uncertain.

Whether subcutaneous fat lacks the pathological obseity of visceral anx or is simply a more neutral storage location, Glutathione for joint health example, Chronic hyperglycemia and obesity further study.

Hyperglyycemia differences in body fat distribution, emerging evidence suggests that different subtypes of Chrohic tissue obesjty be functionally distinct Flexibility training for runners affect xnd homeostasis differentially.

Adult humans have limited and variable numbers Chonic brown obesitty cells 4which play a role in thermogenesis and potentially influence energy expenditure and obesity susceptibility 5. Improved obrsity of the function of different fat cell types and annd and their roles in metabolic homeostasis is a priority hypervlycemia investigation into the pathogenesis and complications of obesity.

Likewise, adipose jyperglycemia is composed of heterogeneous cell types. Immune cells within anr tissue also likely contribute to systemic hyperglyccemia processes. As the study Prebiotics and immune system adipose biology progresses, it will be hypergoycemia to consider whether additional subtypes anx adipocytes or other cell types can be hyperglcemia to refine our understanding of anv complications and generate Chfonic approaches to gyperglycemia.

Mitochondrial obesitj could be one of Chronic hyperglycemia and obesity important underlying defects linking obesity to diabetes, both by decreasing hypwrglycemia sensitivity and by compromising β-cell hyperglyycemia.

Although mechanisms underlying this coupling e. Znd glucose intolerance reflects failure to mount one or more of these compensatory responses Factors predisposing to β-cell decompensation could also be primarily genetic or epigenetic. A clear, mechanistic basis for this decompensation has remained elusive.

Genetic studies have helped identify the role of some key molecules in β-cell biology that may be important in this regard. For example, recent rodent studies have demonstrated diabetogenic effects of reduced pancreatic expression of the Pdx1 gene 14 While these animal studies have demonstrated that PDX1 deficiency relates mechanistically to diabetes through β-cell apoptosis, and PDX1 deficiency is linked to MODY4 16it is not clear yet that PDX1 deficiency has a role in common forms of type 2 diabetes htperglycemia humans.

This example illustrates how a growing understanding of genetics and cellular function of the β-cell can identify potential mediators predisposing obese individuals to type 2 diabetes and further may provide insights for the development of new therapeutic agents. Most type 2 diabetes genes appear to be related to β-cell dysfunction, with many fewer involved in pathways related to insulin resistance independent of obesity 19 Not surprisingly, many obesity gene variants appear to be involved in pathways affecting energy homeostasis.

Although additional genes with important roles will hyperglycsmia be discovered, this low predictive power may reflect the importance of environmental factors, less frequent genetic variants with stronger effects, or gene-environment, gene-gene, and epigenetic interactions that are not readily identified through methods based on population genetics.

Methods for detecting gene-gene interactions exist, but the population size needed to detect them is substantially greater than is required for detection of single genes of relatively small effect.

Alternatively, pathway analyses or a systems biology approach combining information from DNA variations with transcript, protein, and metabolite profiles may better capture the genetic influences on metabolism than studying single genes.

One should also keep in mind that the missing heritability could be an illusion of inferring additive genetic effects from epidemiological data Although the link between obesity and type 2 diabetes is widely held to involve two discrete lesions—obesity-induced insulin resistance and β-cell failure—both disorders may share an underlying defect.

One potential link could be sustained cell exposure to nutrient concentrations exceeding energy requirements. These responses are not mutually exclusive, and induction of one may trigger another, leading to a cascade of damage. Obesity-associated cellular injury can in turn recruit and activate macrophages and other immune cells that exacerbate tissue inflammation 23 Collectively, these responses contribute to the pathogenesis of insulin resistance in the liver, skeletal muscle, and adipose tissue, and some e.

In susceptible individuals, therefore, obesity-induced metabolic impairment can favor insulin resistance on the one hand and progressive β-cell dysfunction on the other. Reduced insulin secretion can in turn worsen the nutrient excess problem by raising circulating concentrations of glucose, free fatty acids, and other nutrients.

In this way, a vicious cycle arises whereby obesity-induced nutrient excess triggers inflammatory responses that cause insulin resistance, placing a greater demand on the β-cell, and as β-cell function declines the cellular toll taken by nutrient excess increases.

Since not all obese individuals develop hyperglycemia, however, an underlying abnormality of the β-cell must coexist with nutrient excess to promote type 2 diabetes Brain neurocircuits governing energy homeostasis also affect insulin sensitivity in the liver and perhaps other peripheral tissues 25and inflammation similar to that induced by obesity in peripheral insulin-sensitive tissues also occurs in these areas of the brain If obesity is associated with impairment of neurocircuits regulating both energy balance and insulin action, obesity-induced insulin resistance may arise not only as a direct consequence of excessive adipose mass but via neuronal mechanisms as well.

Whether disturbed neurocircuits also contribute to deteriorating β-cell dysfunction as obesity and its sequelae progress is an active area of investigation The dramatic increase in incidence and prevalence of obesity over the past 50 years, associated in part with major worldwide changes in caloric intake and dietary composition, has focused attention on lifestyle intervention to reverse or ameliorate caloric imbalance.

Some longer-term lifestyle intervention studies with sustained interventions demonstrate more durable weight loss 2829with extent of weight loss in the first 3—6 months generally predicting longer-term success. Successful lifestyle intervention programs typically involve self-monitoring of weight, dietary intake, and activity; behavioral modification; frequent contact; and caloric balance through diet, with or without exercise.

For example, short-term intervention studies suggest that dietary changes, which emphasize less fat and refined carbohydrates, make it easier to reduce total caloric intake in obese adults and overweight children 30 Medications have been used to assist in weight loss for almost 80 years, but adverse effects frequently restrict utility.

Medications have been developed based on physiological insights, more recently targeting central nervous system control of appetite and metabolism, or opportunistically when weight loss was noted as a side effect of approved medications.

Table 1 lists medications that have been available and others under development. However, most drug trials last only 6—12 months, and thus there are few long-term data that weight loss can be sustained. Furthermore, concern regarding adverse effects, including cardiovascular disease risk and central effects e.

EMA, European Medicines Agency; FDA, U. Food and Drug Administration; GLP-1, glucagon-like peptide 1. Phentermine is one of a class of sympathomimetic drugs that also includes benzphetamine, diethylpropion, and phendimetrazine.

Health benefits of bariatric surgery, determined largely from nonrandomized studies, are being increasingly recognized. These benefits include substantial and sustained weight loss 32resolution of comorbidities such as diabetes, hypertension, and dyslipidemia 3334and reduced myocardial infarction, cancers, and associated mortality For extreme obesity, surgery is now the preferred and currently only effective treatment modality.

Acute morbidity and mortality of surgical approaches have been dramatically reduced, enabling widespread use of these procedures. Furthermore, over the long term, bariatric surgery might reduce aggregate health care expenditures There is also a growing movement toward using surgery to control diabetes, independent of severe excess weight, but there are currently few scientifically valid data to support this clinical path.

Bariatric surgery falls into two general categories: purely restrictive procedures such as the laparoscopic adjustable gastric band devices, which appear to improve diabetes via weight loss, and procedures bypassing the proximal gut, such as the Roux-en-Y gastric bypass RYGB or newer gastric sleeve procedures.

Metabolic surgeries are associated with increases in anorexigenic and decreases in orexigenic hormones, changes largely absent in band or restrictive procedures, and may explain the differential outcomes Although mechanisms leading to weight loss and diabetes remission are only beginning to be understood, the above endocrine, peptide, and neural effects may mediate these benefits because of structural changes including isolation of the gastric cardia; exclusion of the distal stomach, duodenum, and proximal jejunum; exposure of the distal intestine to undigested nutrients; and partial vagotomy.

Longer duration of diabetes and insulin use, both typically associated with decreased β-cell function and possibly surrogates for reduced β-cell mass, are associated with reduced postsurgical remission rates, thus suggesting that residual β-cell function may be a critical factor for metabolic benefits Known differences in mechanism and efficacy, along with risks and patient priorities e.

However, many questions remain, including the following: How much weight loss is required for health benefits? What is the effect of different interventional methods on long-term outcomes?

What mechanisms underlie the heterogeneous responses? Further, regarding diabetes, Is the optimal timing for treatment the same or different from obesity? Are β-cells preserved or do they even grow? Why do not we see the same efficacy and durability of response for other obesity-related pathologies e.

Ongoing randomized clinical trials 40 promise to answer many questions regarding patient selection, optimal procedure, when to intervene, and where initial and chronic care should be delivered.

A vast array of barriers—ranging from deficits in basic research to socioeconomic and individual psychological factors beyond the scope of the conference—undermines current efforts to manage obesity, particularly in individuals with type 2 diabetes.

Lessons learned from efforts such as those applied to tobacco cessation may be quite relevant Lifestyle programs especially long-term are often plagued by inadequate reimbursement. Further, there is a lack of evidence-based individualized goals and strategies combining lifestyle and medications, or appreciation of sequential stepped therapy.

As mechanisms leading to obesity and its maintenance are not fully understood, questions remain about which interventions, be they lifestyle or pharmacological, might be most effective during various stages of weight gain, loss, and regain.

In addition, medications under development may carry indeterminate risk. Likewise, surgery is an imperfect remedy due in part to perceived risks and high cost.

: Chronic hyperglycemia and obesity

Acknowledgments

This is consistent with guidelines from the American Diabetes Association ADA and the European Association for the Study of Diabetes EASD consensus guideline for medical management of hyperglycemia and underscores the importance of avoiding delay in treatment intensification figure 1 [ 1,2 ].

In some patients, early combination therapy is warranted for the kidney or heart protective benefit imparted by selected classes of glucose-lowering medications. See 'Established cardiovascular or kidney disease' below and "Sodium-glucose cotransporter 2 inhibitors for the treatment of hyperglycemia in type 2 diabetes mellitus", section on 'Patient selection' and "Glucagon-like peptide 1-based therapies for the treatment of type 2 diabetes mellitus", section on 'Patient selection'.

Glycemic goals — Target A1C goals in patients with type 2 diabetes should be tailored to the individual, balancing the prospect of reduced microvascular complications with the adverse effects and cost of added treatments.

Glycemic targets are reviewed in more detail separately. See "Glycemic control and vascular complications in type 2 diabetes mellitus", section on 'Choosing a glycemic target'. Related Pathway s : Diabetes: Medication selection for non-pregnant adults with type 2 DM and persistent hyperglycemia despite monotherapy.

See 'Without established cardiovascular or kidney disease' below. Causes of rising glycemia — Among the factors that can contribute to worsening glycemia are:.

See "Classification of diabetes mellitus and genetic diabetic syndromes", section on 'Latent autoimmune diabetes in adults LADA '. A population-based study of over patients with type 2 diabetes demonstrated that many patients have A1C levels higher than ideal for years owing to a delay in or absence of medication changes to improve glycemic management [ 12 ].

Adherence to algorithms that dictate changes in treatment at designated intervals and computerized decision aids may improve A1C more efficiently than standard care [ 14,16,17 ]. OUR APPROACH — The therapeutic options for patients who have deterioration of glycemic management on initial therapy with lifestyle intervention and metformin are to add a second oral or injectable agent, including addition of insulin as an option, or to switch to insulin table 2.

Our approach outlined below is largely consistent with American and European guidelines [ 1,2,18 ]. The guidelines emphasize the importance of individualizing the choice of medications for the treatment of diabetes, considering important comorbidities including cardiovascular disease [CVD], heart failure HF , diabetic kidney disease DKD , hypoglycemia risk, and need for weight loss and patient-specific factors including patient preferences, needs, values, and cost.

We also agree with the World Health Organization WHO guidelines that sulfonylureas have a long-term safety profile, are inexpensive, and are highly effective, especially when used as described below, with patient education and dose adjustment to minimize side effects [ 19 ].

Short-acting sulfonylureas are preferred to reduce the risk of hypoglycemia. Our selection of drugs described below is based upon clinical trial evidence and clinical experience in achieving glycemic targets, with the recognition that there are few high-quality, longer-term, head-to-head drug comparison trials, particularly trials examining clinically important health outcomes cardiovascular events, mortality in patients without existing or multiple risk factors for atherosclerotic CVD ASCVD.

In a network meta-analysis of trials evaluating the effects of selected metformin-based combinations on A1C, mortality, and vascular outcomes in a heterogeneous group of patients with variable cardiovascular risk, the greatest reduction in A1C was seen with the addition of glucagon-like peptide 1 GLP-1 receptor agonists, premixed insulin, basal-bolus insulin, basal insulin, or prandial insulin reductions in A1C ranging from For patients at low cardiovascular risk, all treatments were similar to placebo for vascular outcomes.

For patients at increased cardiovascular risk, oral semaglutide, empagliflozin , and liraglutide all compared with placebo reduced all-cause mortality and cardiovascular death odds ratios [ORs] ranging from 0.

Sodium-glucose co-transporter 2 SGLT2 inhibitors, in general, had favorable effects on hospitalization for HF and progression of renal disease. In other meta-analyses, metformin combination therapy decreased A1C levels more than metformin monotherapy by approximately 1 percentage point [ 21,22 ].

Most combinations similarly reduced A1C. Moderate evidence favored metformin plus a GLP-1 receptor agonist over metformin plus a dipeptidyl peptidase 4 DPP-4 inhibitor for reducing A1C levels [ 21 ].

As expected, the use of thiazolidinediones, sulfonylureas, and insulin was associated with weight gain, while metformin, GLP-1 receptor agonists, SGLT2 inhibitors, and DPP-4 inhibitors were associated with weight loss or weight maintenance. Sulfonylureas were associated with higher rates of hypoglycemia.

Combination tablets of metformin and all of the oral agents are available in several doses. For patients who are doing well on these particular doses, the combination tablets offer the convenience of taking fewer pills.

However, if the patient requires that the dose of either drug be changed independent of the other drug, then a fixed combination is unhelpful. In addition, the cost of the brand name combinations is substantially greater than the generic components individually. Monotherapy failure — For patients with deterioration of glycemic management while taking initial oral monotherapy, many available medication classes can be used with metformin or in combination with each other if metformin is contraindicated or not tolerated.

Related Pathway s : Diabetes: Medication selection for non-pregnant adults with type 2 DM and persistent hyperglycemia despite monotherapy and Diabetes: Initiation and titration of insulin therapy in non-pregnant adults with type 2 DM.

Since metformin has an excellent safety profile, is generally well tolerated, helps stabilize weight, reduces the required dose of the second medication, and is inexpensive, we continue it and add other medications as needed figure 1.

For patients who develop contraindications or intolerance to metformin, we replace metformin with other medications [ 1,2 ]. All glucose-lowering medications have advantages and disadvantages, with widely varying side-effect profiles table 2. All of the newer medicines that are not available in generic form are relatively expensive.

For patients with persistent hyperglycemia while taking metformin mg per day or a lower maximally tolerated dose , the choice of a second medication should be individualized based on efficacy, risk for hypoglycemia, the patient's comorbid conditions, impact on weight, side effects, and cost.

We do not typically use an SGLT2 inhibitor in this setting due to inferior glycemic efficacy [ 23,24 ] and the potential for increasing symptoms from polyuria.

Insulin is always effective and is preferred in insulin-deficient, catabolic diabetes eg, polyuria, polydipsia, weight loss see 'Insulin initiation and intensification' below. While basal insulin has historically been the preferred medication to add to metformin when A1C is markedly elevated even in the absence of catabolic symptoms , GLP-1 receptor agonists are an effective alternative to basal insulin when type 1 diabetes is not likely.

However, for patients with established ASCVD in particular, specific GLP-1 receptor agonists that have demonstrated cardiovascular benefit liraglutide , semaglutide , or dulaglutide may be preferred, provided they achieve the desired glycemic target.

Gastrointestinal GI side effects and contraindications to GLP-1 receptor agonists, as well as cost, may limit their use. See "Glucagon-like peptide 1-based therapies for the treatment of type 2 diabetes mellitus", section on 'Cardiovascular effects' and "Glucagon-like peptide 1-based therapies for the treatment of type 2 diabetes mellitus", section on 'Adverse effects'.

However, longer-acting analogs are similar to NPH with regard to total or severe hypoglycemia and have the important disadvantage of higher cost. These data are reviewed separately. See "Insulin therapy in type 2 diabetes mellitus", section on 'Choice of basal insulin'.

Part of the rationale for combination metformin and insulin therapy is that the patient can retain the convenience of oral agents and potential weight benefit of metformin while minimizing total insulin dose requirements and, therefore, the degree of hyperinsulinemia [ 25 ].

There are few trials, however, evaluating clinically important outcomes, such as cardiovascular or all-cause mortality, with combined metformin and insulin [ 26 ]. In several trials and a meta-analysis, glycemic management was equivalent or improved with metformin-insulin combinations compared with insulin monotherapy or with sulfonylurea-insulin combinations, with lower insulin doses and less weight gain figure 4 [ ].

In the United Kingdom Prospective Diabetes Study UKPDS , the combination of insulin with metformin was also associated with significantly less weight gain than twice-daily insulin injections or insulin combined with sulfonylureas [ 30 ].

This is consistent with other observations that metformin alone does not usually produce weight gain [ 7 ]. Combining insulin and sulfonylurea is usually not endorsed, as they have similar mechanisms of action providing more insulin , and the same glucose-lowering effect can usually be achieved with a modestly higher dose of insulin alone.

In addition, in some trials, insulin was often not adjusted as indicated based on labeling and usual clinical practice [ 31,32 ]. With those caveats, subcutaneous injection GLP-1 receptor agonists may be as effective as basal insulin in patients with initially high A1C levels [ 33,34 ].

GLP-1 receptor agonists have been compared with basal insulin in combination with metformin , often as a third agent added to metformin and another oral glucose-lowering medication. In most of these trials, GLP-1 receptor agonists have achieved at least equivalent glycemic management as the addition of basal insulin with the added benefit of weight loss, rather than weight gain, as is often seen with basal insulin.

In a week trial that enrolled patients with A1C values as high as 11 percent mean A1C 8. These trials are reviewed separately.

See "Glucagon-like peptide 1-based therapies for the treatment of type 2 diabetes mellitus". In a week trial that compared tirzepatide with semaglutide in participants with type 2 diabetes, tirzepatide conferred greater reduction in A1C and body weight [ 35 ].

Clinical data are not yet available to establish whether tirzepatide also provides the cardiovascular or kidney protective benefits shown for some GLP-1 receptor agonists. Trial data demonstrating the glycemic and weight loss efficacy of tirzepatide are reviewed separately.

See "Glucagon-like peptide 1-based therapies for the treatment of type 2 diabetes mellitus", section on 'Clinical outcomes'. Data from small trials demonstrate substantial inter-individual variability in treatment response to specific medications for endpoints including glycemia and reduction in albuminuria [ 36,37 ], further underscoring the importance of individualized therapy.

Established cardiovascular or kidney disease — For patients with existing ASCVD, HF, or albuminuric DKD, a glucose-lowering medication with evidence of cardiac or kidney benefit should be added to metformin algorithm 2. SGLT2 inhibitors with cardiovascular benefit empagliflozin or canagliflozin are good alternatives.

See "Glucagon-like peptide 1-based therapies for the treatment of type 2 diabetes mellitus", section on 'Cardiovascular effects'. In the setting of declining eGFR, the main reason to prescribe an SGLT2 inhibitor is to reduce progression of DKD. However, cardiac and kidney benefits have been shown in patients with eGFR below this threshold.

See "Treatment of diabetic kidney disease", section on 'Type 2 diabetes: Treat with additional kidney-protective therapy'. In the absence of randomized trials directly comparing cardiovascular outcomes of the GLP-1 receptor agonists and SGLT2 inhibitors, the following findings and those from network meta-analyses [ 38,39 ] largely support our approach outlined above:.

See "Sodium-glucose cotransporter 2 inhibitors for the treatment of hyperglycemia in type 2 diabetes mellitus", section on 'Cardiovascular effects'.

Patients at high CVD risk but without a prior event might benefit, but the data are less definitive [ 45 ]. Similarly, patients without severely increased albuminuria derive some benefit, but the absolute benefits are greater among those with severely increased albuminuria.

For the other primary outcome a composite of hospitalization for myocardial infarction or stroke , there was a small benefit with SGLT2 inhibitors in patients with a history of CVD rate difference There was no difference in CVD outcomes between the two classes in those without a history of CVD.

GLP-1 receptor agonists are an alternative since glycemic benefit is independent of kidney function. In addition, GLP-1 receptor agonists have been shown to slow the rate of decline in eGFR and prevent worsening of albuminuria, albeit to a lesser degree than SGLT2 inhibitors. GLP-1 receptor agonists should be titrated slowly, with monitoring for GI side effects, which could precipitate dehydration and acute kidney injury AKI.

See "Sodium-glucose cotransporter 2 inhibitors for the treatment of hyperglycemia in type 2 diabetes mellitus" and "Glucagon-like peptide 1-based therapies for the treatment of type 2 diabetes mellitus", section on 'Microvascular outcomes'. We avoid use of SGLT2 inhibitors in patients with frequent genitourinary yeast infections or bacterial urinary tract infections, low bone density and high risk for falls and fractures, foot ulceration, and factors predisposing to diabetic ketoacidosis eg, pancreatic insufficiency, drug or alcohol use disorder because of increased risk for each while using these agents.

SGLT2 inhibitors should be held for procedures, colonoscopy preparation, and with poor oral intake to prevent diabetic ketoacidosis. See "Sodium-glucose cotransporter 2 inhibitors for the treatment of hyperglycemia in type 2 diabetes mellitus", section on 'Contraindications and precautions'.

In general, we tolerate higher glycemic targets, and, if medication is required, we prefer a short-acting, low-dose sulfonylurea eg, glipizide , repaglinide , linagliptin , or cautious use of a GLP-1 receptor agonist or insulin.

See "Management of hyperglycemia in patients with type 2 diabetes and advanced chronic kidney disease or end-stage kidney disease", section on 'Treatment' and "Sulfonylureas and meglitinides in the treatment of type 2 diabetes mellitus", section on 'Use in chronic kidney disease' and "Sulfonylureas and meglitinides in the treatment of type 2 diabetes mellitus", section on 'Clinical use of meglitinides'.

Without established cardiovascular or kidney disease — For most patients without established ASCVD or kidney disease who have persistent hyperglycemia while taking metformin mg per day or a lower maximally tolerated dose , we suggest a GLP-1 receptor agonist or basal insulin based on the results of the GRADE trial, a comparative effectiveness study of commonly used classes of glucose lowering medications algorithm 2 [ 10,54 ].

In the GRADE trial, choice of a second glucose-lowering medication was evaluated in patients with type 2 diabetes A1C 6. Participants with hyperglycemia despite taking maximum tolerated doses of metformin were randomly assigned to treatment with U glargine, liraglutide , glimepiride , or sitagliptin.

Over a mean follow-up of five years, all four medications lowered A1C levels. The proportion of individuals with severe hypoglycemia was highest in the glimepiride group 2. Liraglutide had the highest frequency of gastrointestinal side effects.

The treatment groups did not differ in the rate of the prespecified secondary micro- or macrovascular outcomes, including moderately or severely increased albuminuria, reduced kidney function, peripheral neuropathy, major adverse cardiovascular events MACE , hospitalization for HF, cardiovascular mortality, or overall mortality [ 54,55 ].

However, there was a small reduction in the incidence of any CVD defined as first incidence of MACE, hospitalization for unstable angina or HF, or revascularization in any arterial bed with liraglutide 6. The GRADE trial was designed and implemented prior to the availability of SGLT2 inhibitors.

SGLT2 inhibitors have lower glycemic efficacy compared with basal insulin and GLP-1 receptor agonists [ 20 ]. The cardiovascular benefit of SGLT2 inhibitors has not been demonstrated in those at low cardiovascular risk.

Shorter-term trial data also support selection of the dual-acting GLP-1 and GIP receptor agonist tirzepatide as a second glucose-lowering agent, particularly in individuals for whom substantial body weight loss is a treatment goal.

Trial data for tirzepatide are reviewed separately. The choice of an alternative glucose-lowering medication is guided by efficacy, patient comorbidities, preferences, side effects, and cost algorithm 2.

These benefits are offset by risks of hypoglycemia and modest weight gain. Sulfonylureas can be used safely and effectively with dose adjustment, even in people at risk of hypoglycemia, but this requires a bit more attention. We prefer a shorter-duration sulfonylurea or one with relatively lower risk for hypoglycemia eg, glipizide , glimepiride , since longer-acting glyburide is associated with a higher risk of hypoglycemia, especially in older or frail patients.

In addition, there are good data providing reassurance of the cardiovascular safety of these sulfonylureas. See "Sulfonylureas and meglitinides in the treatment of type 2 diabetes mellitus", section on 'Cardiovascular effects'.

The glycemic efficacy of sulfonylureas in combination with other oral agents is illustrated by the findings of a meta-analysis of trials in which sulfonylureas were added to oral agents predominantly metformin or thiazolidinediones [ 56 ]. Compared with placebo, the addition of sulfonylureas to oral diabetes treatment lowered A1C by 1.

The clinical use, side effects, and concerns about the cardiovascular safety of sulfonylureas are reviewed separately. See "Sulfonylureas and meglitinides in the treatment of type 2 diabetes mellitus".

SGLT2 inhibitors are associated with modest weight loss. With both medication classes, weight loss effects are stronger when the medication is combined with sustained efforts at dietary modification. In patients with diabetes mellitus and biopsy-proven NASH, pioglitazone has been shown to improve fibrosis as well as inflammation and steatosis.

GLPbased therapies also appear to improve liver biopsy evidence of NASH. These studies are reviewed in detail separately. See "Management of nonalcoholic fatty liver disease in adults", section on 'Patients with NASH and diabetes'. The potential benefits of these drugs must be balanced with their associated adverse effects.

In particular, pioglitazone is not typically a first-choice agent due to adverse effects, including increased risk of weight gain, fluid retention, HF, fractures, and the potential increased risk of bladder cancer.

It may play a role in the treatment of selected patients with severe insulin resistance, NASH or nonalcoholic fatty liver disease , at low risk of fracture. Adverse effects of pioglitazone may be minimized by using 15 to 30 mg rather than the 45 mg highest dose.

See "Management of nonalcoholic fatty liver disease in adults", section on 'Patients with NASH and diabetes' and "Thiazolidinediones in the treatment of type 2 diabetes mellitus", section on 'Safety' and "Glucagon-like peptide 1-based therapies for the treatment of type 2 diabetes mellitus", section on 'Adverse effects'.

Trials comparing other combinations are reviewed separately in the individual topics. See "Glucagon-like peptide 1-based therapies for the treatment of type 2 diabetes mellitus", section on 'Glycemic efficacy' and "Dipeptidyl peptidase 4 DPP-4 inhibitors for the treatment of type 2 diabetes mellitus", section on 'Glycemic efficacy' and "Sodium-glucose cotransporter 2 inhibitors for the treatment of hyperglycemia in type 2 diabetes mellitus", section on 'Glycemic efficacy'.

Dual agent failure — For patients who have deterioration of glycemic management on dual therapy, the options include:. Although guidelines suggest combining SGLT2 inhibitors and GLP-1 receptor agonists [ 1 ], we do not usually add an SGLT2 inhibitor to GLP-1 receptor agonist therapy for hyperglycemia alone given the absence of data showing additive cardiovascular and kidney benefit and increased patient burden cost, polypharmacy, adverse effects.

The choice of additional therapy should be individualized, as discussed above for patients with monotherapy failure, based on efficacy, glycemic target, risk of hypoglycemia, the patient's underlying comorbidities, impact on weight, side effects, and cost.

See 'Monotherapy failure' above. In patients on sulfonylureas and metformin who are starting insulin therapy, sulfonylureas are generally discontinued, while metformin is continued.

In patients on a DPP-4 inhibitor who are starting a GLP-1 receptor agonist or dual-acting GLP-1 and GIP receptor agonist, the DPP-4 inhibitor should be discontinued. Insulin dose requirements can decrease precipitously with the addition of these medications, requiring patient education and close follow-up with insulin dose adjustment in the short term to reduce the risk of hypoglycemia.

See "Glucagon-like peptide 1-based therapies for the treatment of type 2 diabetes mellitus", section on 'Cardiovascular effects' and "Sodium-glucose cotransporter 2 inhibitors for the treatment of hyperglycemia in type 2 diabetes mellitus", section on 'Cardiovascular effects'.

In a meta-analysis of randomized trials evaluating the addition of a third agent in patients inadequately managed with two agents predominantly metformin and a sulfonylurea or metformin and a thiazolidinedione , triple-agent combinations reduced A1C to a greater extent than two agents [ 58 ].

In trials lasting 52 to 54 weeks, the addition of thiazolidinediones, GLP-1 receptor agonists, or SGLT2 inhibitors to metformin and sulfonylurea reduced A1C to a similar extent, and tirzepatide imparted even greater A1C reduction.

However, these trials did not directly compare the third-line agents with each other. Moreover, only the GRADE study was of sufficient duration to determine long-term glycemic effects.

For patients who are not well managed on two oral agents, switching to insulin may be less expensive than adding a third oral or injectable agent, depending on which insulin and which third oral or injectable agent is selected.

Insulin initiation and intensification — If a decision has been made to add insulin to oral hypoglycemic therapy in patients with type 2 diabetes, a single daily dose of either insulin NPH or detemir given at bedtime or insulin glargine or degludec given in the morning or at bedtime is a reasonable initial regimen [ 1 ].

Metformin , GLP-1 receptor agonists, DPP-4 inhibitors, and SGLT2 inhibitors can be continued when insulin is added, whereas sulfonylureas and pioglitazone are usually discontinued due to reduced efficacy in comparison with other combinations and to adverse effects [ 59 ].

Patients should measure blood glucose at appropriate times, and usually once to twice per day, depending on the insulin used and timing of administration.

For example, if bedtime NPH is used, it should be adjusted based on fasting glucose levels. More frequent self-monitoring should be implemented during insulin dose adjustment and when changes in daily activities traveling, changes in diet or exercise pattern or acute illness makes insulin adjustments necessary.

The dose of basal or long-acting insulin may be adjusted every three to four days until fasting glucose targets are achieved. Once an insulin regimen is stable, less frequent glucose monitoring may suffice. See "Insulin therapy in type 2 diabetes mellitus", section on 'Titrating dose'.

Related Pathway s : Diabetes: Initiation and titration of insulin therapy in non-pregnant adults with type 2 DM. For patients who continue to have poor glycemic management on basal insulin after titration, diet and exercise patterns should be reviewed.

Potential next steps include adding rapid-acting insulin before the largest meal and then two or three meals if needed , adding a GLP-1 receptor agonist, or changing to premixed insulin twice daily figure 5. Several premixed combinations of basal and prandial insulin or basal insulin and a GLP-1 receptor agonist are available.

See "Insulin therapy in type 2 diabetes mellitus", section on 'Designing an insulin regimen' and "General principles of insulin therapy in diabetes mellitus" and "Glucagon-like peptide 1-based therapies for the treatment of type 2 diabetes mellitus".

Use of an intensive insulin regimen with multiple daily injections MDI; similar to that used in type 1 diabetes may be necessary in insulin-deficient type 2 diabetes.

Patients with type 2 diabetes on MDI or with insulin deficiency may benefit from devices used more commonly in type 1 diabetes such as insulin pumps or continuous glucose monitors. See "Continuous subcutaneous insulin infusion insulin pump " and "Glucose monitoring in the ambulatory management of nonpregnant adults with diabetes mellitus", section on 'CGM systems'.

MDI results in higher serum insulin concentrations and better glycemic management than that achieved with either an oral drug or basal insulin therapy alone [ 7 ]. MDI in type 2 diabetes may require large doses of insulin to overcome insulin resistance and can be associated with substantial weight gain averaging 8.

Patients with type 2 diabetes with generalized obesity or with central overweight, often with nonalcoholic fatty liver disease, frequently require insulin doses in the range of 65 to units per day or much higher.

Although the total daily dose of insulin may be high, the insulin dose per kilogram is less remarkable. Accessed Dec. Melmed S, et al. Williams Textbook of Endocrinology.

Elsevier; Diabetes overview. National Institute of Diabetes and Digestive and Kidney Diseases. Type 2 diabetes. Mayo Clinic; Feldman M, et al. Surgical and endoscopic treatment of obesity. In: Sleisenger and Fordtran's Gastrointestinal and Liver Disease: Pathophysiology, Diagnosis, Management.

Accessed Oct. Hypersmolar hyperglycemic state HHS. Diabetic ketoacidosis DKA. National Center for Complementary and Integrative Health. Type 2 diabetes and dietary supplements: What the science says. Preventing diabetes problems.

Schillie S, et al. Prevention of hepatitis B virus infection in the United States: Recommendations of the Advisory Committee on Immunization Practices. MMWR Recommendations and Reports. Related Caffeine: Does it affect blood sugar? Diabetes prevention: 5 tips for taking control GLP-1 agonists: Diabetes drugs and weight loss Hyperinsulinemia: Is it diabetes?

Medications for type 2 diabetes Show more related content. Associated Procedures A1C test Bariatric surgery Endoscopic sleeve gastroplasty Gastric bypass Roux-en-Y Glucose tolerance test Show more associated procedures. News from Mayo Clinic Mayo study uses electronic health record data to assess metformin failure risk, optimize care Feb.

CDT Mayo Clinic Minute: Strategies to break the heart disease and diabetes link Nov. CDT Mayo Clinic Q and A: Diabetes risk in Hispanic people Oct. CDT The importance of diagnosing, treating diabetes in the Hispanic population in the US Sept. CDT Mayo Clinic Minute: Managing Type 2 diabetes Sept. CDT Expert Alert: Mayo Clinic Healthcare cardiologist explains link between diabetes, heart disease March 23, , p.

CDT Show more news from Mayo Clinic. Mayo Clinic Press Check out these best-sellers and special offers on books and newsletters from Mayo Clinic Press. Mayo Clinic on Incontinence - Mayo Clinic Press Mayo Clinic on Incontinence The Essential Diabetes Book - Mayo Clinic Press The Essential Diabetes Book Mayo Clinic on Hearing and Balance - Mayo Clinic Press Mayo Clinic on Hearing and Balance FREE Mayo Clinic Diet Assessment - Mayo Clinic Press FREE Mayo Clinic Diet Assessment Mayo Clinic Health Letter - FREE book - Mayo Clinic Press Mayo Clinic Health Letter - FREE book.

Show the heart some love! Give Today. Help us advance cardiovascular medicine. Find a doctor. Explore careers.

Sign up for free e-newsletters. About Mayo Clinic. Individuals affected by excess weight, particularly obesity and morbid obesity, are more likely to develop type 2 diabetes as a related condition of their excess weight.

Obesity and morbid obesity greatly increase your risk of having heart disease, type 2 diabetes, certain types of cancer, sleep apnea, osteoarthritis and much more. What you consume throughout your day and how active you are affects your risk of developing type 2 diabetes.

Being overweight BMI of The more excess weight you have, the more resistant your muscle and tissue cells become to your own insulin hormone. In addition to excess weight, there are many other factors that increase your risk of developing type 2 diabetes, such as:. Inactivity and being overweight go hand-in-hand with a diagnosis of type 2 diabetes.

Muscle cells have more insulin receptors than fat cells, so an individual can decrease insulin resistance by exercising. Being more active also lowers blood sugar levels by helping insulin to be more effective. Unhealthy eating is a contributor to obesity.

Too much fat in your diet, not enough fiber and too many simple carbohydrates all contribute to the development of type 2 diabetes. It appears that people who have family members with type 2 diabetes are at a greater risk for developing it themselves. Asians, Pacific Islanders, American Indians, Alaskans, African Americans and Hispanics all have a higher than normal rate of type 2 diabetes.

As we age, the risk of type 2 diabetes becomes greater. Even if an elderly person is thin, they still may be predisposed to developing diabetes. The pancreas ages right along with us and doesn't pump insulin as efficiently as it did when we were younger.

As our cells age, they become more resistant to insulin as well. These two factors are the hallmark risk factors for many diseases and conditions, including type 2 diabetes. Not only do they damage heart vessels, but they are two key components in metabolic syndrome, a cluster of symptoms including obesity, a high fat diet and lack of exercise.

Having metabolic syndrome increases the risk of heart disease, stroke and type 2 diabetes. Women affected by obesity are more insulin resistant when compared to women of normal weight. There are a variety of blood tests that may indicate whether you have type 2 diabetes.

Let's take a look at each test and see what different results could mean for you and your health. The amount of sugar in your blood naturally fluctuates but stays within a normal range. The preferred way to test your blood sugar is after you've fasted overnight for at least eight hours.

A fasting blood sugar level less than milligrams of sugar per deciliter of blood is considered normal. If your blood sugar level measures from to , you have impaired fasting glucose, and this may be an indication that you have pre-diabetes. This test is done without any special preparation, such as fasting overnight.

If it is and you also have symptoms of type 2 diabetes, you can expect a diagnosis of type 2 diabetes. This test requires you to visit a lab or a healthcare professional after at least an eight-hour fast.

At the office or lab, you will drink about eight ounces of a sweet liquid that contains a lot of sugar about 75 grams. Your blood sugar level will be measured before you drink the liquid, then after one hour and again after two hours.

Losing weight is one of the most beneficial ways you can help prevent type 2 diabetes. For many individuals, simply adjusting their caloric intake and beginning an exercise program can greatly improve their type 2 diabetes and overall health.

Weight loss occurs when energy expenditure exceeds energy intake.

Type 2 diabetes - Symptoms and causes - Mayo Clinic

Worldwide trends in diabetes since a pooled analysis of population-based studies with 4. Download references. Department of Medicine, University of Leipzig, Leipzig, Germany. You can also search for this author in PubMed Google Scholar.

Correspondence to Michael Stumvoll. Division of Endocrinology, Diabetes and Metabolism, University and Hospital Trust of Verona, Verona, Italy. Diabetes Division, Diabetes Research Unit, University of Texas Health Science Center, San Antonio, TX, USA. Reprints and permissions.

Blüher, M. Diabetes and Obesity. In: Bonora, E. eds Diabetes Complications, Comorbidities and Related Disorders. Springer, Cham. Published : 01 April Publisher Name : Springer, Cham. Print ISBN : Online ISBN : eBook Packages : Medicine Reference Module Medicine.

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References American Diabetes Association ADA. Google Scholar American Diabetes Association ADA. Google Scholar Anderson JW, Konz EC, Frederich RC, Wood CL. Article CAS PubMed Google Scholar Apovian CM, Aronne LJ, Bessesen DH, McDonnell ME, Murad MH, Pagotto U, Ryan DH, Still CD.

Article CAS PubMed Google Scholar Belfort R, Mandarino L, Kashyap S, et al. Article CAS PubMed Google Scholar Bjorntorp P. Article CAS PubMed Google Scholar Blüher M.

Article Google Scholar Boden G, Shulman GI. Article CAS Google Scholar Bray GA, Frühbeck G, Ryan DH, Wilding JP. Article PubMed Google Scholar Brunzell JD, Robertson RP, Lerner RL, Hazzard WR, Ensinck JW, Bierman EL, Porte D Jr. Article CAS PubMed Google Scholar Buchwald H, Estok R, Fahrbach K, Banel D, Jensen MD, Pories WJ, et al.

Article PubMed Google Scholar Cancello R, Henegar C, Viguerie N, Taleb S, Poitou C, Rouault C, Coupaye M, Pelloux V, Hugol D, Bouillot JL, Bouloumié A, Barbatelli G, Cinti S, Svensson PA, Barsh GS, Zucker JD, Basdevant A, Langin D, Clément K.

Article CAS PubMed Google Scholar Chang SH, Stoll CR, Song J, Varela JE, Eagon CJ, Colditz GA. Article PubMed PubMed Central Google Scholar Cinti S. Article CAS PubMed PubMed Central Google Scholar Cinti S, Mitchell G, Barbatelli G, Murano I, Ceresi E, Faloia E, Wang S, Fortier M, Greenberg AS, Obin MS.

Article CAS PubMed Google Scholar Cohen P, Spiegelman BM. Article CAS PubMed PubMed Central Google Scholar Colditz GA, Willett WC, Rotnitzky A, Manson JE. Article CAS PubMed Google Scholar Cypess AM, Lehman S, Williams G, Tal I, Rodman D, Goldfine AB, Kuo FC, Palmer EL, Tseng YH, Doria A, Kolodny GM, Kahn CR.

Article CAS PubMed PubMed Central Google Scholar DeFronzo RA. Article CAS PubMed PubMed Central Google Scholar Despres JP, Nadeau A, Tremblay A, et al. Article CAS PubMed Google Scholar Drucker DJ, Nauck MA. Article CAS PubMed Google Scholar Farooqi IS, et al. Article CAS PubMed Google Scholar Fasshauer M, Blüher M.

Article CAS PubMed Google Scholar Franks PW, McCarthy MI. Article CAS PubMed Google Scholar Frayling TM, Timpson NJ, Weedon MN, Zeggini E, Freathy RM, Lindgren CM, et al.

Article CAS PubMed PubMed Central Google Scholar Gadde KM, Allison DB, Ryan DH, et al. Article CAS PubMed Google Scholar GBD Mortality and Causes of Death Collaborators. Article Google Scholar Gloyn AL, Weedon MN, Owen KR, et al.

Article CAS PubMed Google Scholar Goldstein BJ. Google Scholar Greenberg I, Stampfer MJ, Schwarzfuchs D, Shai I, DIRECT Group. Article CAS PubMed Google Scholar Gudzune KA, Doshi RS, Mehta AK, et al.

Article PubMed PubMed Central Google Scholar Haase J, Weyer U, Immig K, Klöting N, Blüher M, Eilers J, Bechmann I, Gericke M. Article CAS PubMed Google Scholar Hauner H. Google Scholar Hu T, Mills KT, Yao L, et al. Article PubMed PubMed Central Google Scholar Huo R, Du T, Xu Y, et al.

Article CAS PubMed Google Scholar Jakicic JM, Egan CM, Fabricatore AN, Look AHEAD Research Group, et al. Article CAS PubMed PubMed Central Google Scholar Johnston BC, Kanters S, Bandayrel K, Wu P, Naji F, Siemieniuk RA, Ball GD, Busse JW, Thorlund K, Guyatt G, Jansen JP, Mills EJ.

Article CAS PubMed Google Scholar Klein S, Fontana L, Young VL, et al. Article CAS PubMed Google Scholar Klöting N, Fasshauer M, Dietrich A, Kovacs P, Schön MR, Kern M, Stumvoll M, Blüher M. Article CAS PubMed Google Scholar Knowler WC, Fowler SE, Hamman RF, Diabetes Prevention Program Research Group, et al.

Article PubMed Google Scholar Konrad D, Rudich A, Schoenle EJ. Article CAS PubMed Google Scholar Kühnen P, Clément K, Wiegand S, Blankenstein O, Gottesdiener K, Martini LL, Mai K, Blume-Peytavi U, Grüters A, Krude H.

Article CAS PubMed Google Scholar Lebovitz HE. Article CAS PubMed Google Scholar LeFevre ML, U. Article PubMed Google Scholar Li SX, Imamura F, Ye Z, Schulze MB, Zheng J, Ardanaz E, Arriola L, Boeing H, Dow C, Fagherazzi G, Franks PW, Agudo A, Grioni S, Kaaks R, Katzke VA, Key TJ, Khaw KT, Mancini FR, Navarro C, Nilsson PM, Onland-Moret NC, Overvad K, Palli D, Panico S, Quirós JR, Rolandsson O, Sacerdote C, Sánchez MJ, Slimani N, Sluijs I, Spijkerman AM, Tjonneland A, Tumino R, Sharp SJ, Riboli E, Langenberg C, Scott RA, Forouhi NG, Wareham NJ.

Article CAS PubMed Google Scholar Moitra J, Mason MM, Olive M, Krylov D, Gavrilova O, Marcus-Samuels B, Feigenbaum L, Lee E, Aoyama T, Eckhaus M, Reitman ML, Vinson C.

Article CAS PubMed PubMed Central Google Scholar Narayan KM, Boyle JP, Thompson TJ, Sorensen SW, Williamson DF. Article CAS PubMed Google Scholar National Institute for Health and Clinical Excellence: Guidance.

Google Scholar National Task Force on the Prevention and Treatment of Obesity. Article PubMed PubMed Central Google Scholar Norris SL, Zhang X, Avenell A, Gregg E, Schmid CH, Lau J. Google Scholar Padwal RS, Pajewski NM, Allison DB, Sharma AM.

Article PubMed Google Scholar Pi-Sunyer X, Astrup A, Fujioka K, Greenway F, Halpern A, Krempf M, Lau DC, le Roux CW, Violante Ortiz R, Jensen CB, Wilding JP, SCALE Obesity and Prediabetes NN Study Group.

Article CAS PubMed Google Scholar Porzio O, Federici M, Hribal ML, et al. Article CAS PubMed PubMed Central Google Scholar Purnell JQ, Hokanson JE, Marcovina SM, Steffes MW, Cleary PA, Brunzell JD.

Article CAS PubMed PubMed Central Google Scholar Ravussin E, Lillioja S, Knowler WC, Christin L, Freymond D, Abbott WG, et al.

Article CAS PubMed Google Scholar Robbins AL, Savage DB. Article CAS PubMed Google Scholar Robertson RP, Harmon J, Tran PO, Tanaka Y, Takahashi H. Article CAS PubMed Google Scholar Rubino F, Nathan DM, Eckel RH, Schauer PR, Alberti KG, Zimmet PZ, Del Prato S, Ji L, Sadikot SM, Herman WH, Amiel SA, Kaplan LM, Taroncher-Oldenburg G, Cummings DE, Delegates of the 2nd Diabetes Surgery Summit.

Article CAS PubMed Google Scholar Ryan D, Heaner M. Article Google Scholar Sacks FM, Bray GA, Carey VJ, Smith SR, Ryan DH, Anton SD, McManus K, Champagne CM, Bishop LM, Laranjo N, Leboff MS, Rood JC, de Jonge L, Greenway FL, Loria CM, Obarzanek E, Williamson DA. Article CAS PubMed PubMed Central Google Scholar Schauer PR, Kashyap SR, Wolski K, Brethauer SA, Kirwan JP, Pothier CE, Thomas S, Abood B, Nissen SE, Bhatt DL.

Article CAS PubMed PubMed Central Google Scholar Schauer PR, Bhatt DL, Kirwan JP, Wolski K, Brethauer SA, Navaneethan SD, Aminian A, Pothier CE, Kim ES, Nissen SE, Kashyap SR, STAMPEDE Investigators.

Article CAS PubMed PubMed Central Google Scholar Schleinitz D, Böttcher Y, Blüher M, Kovacs P. Article CAS PubMed Google Scholar Schwartz MW, Woods SC, Porte D Jr, Seeley RJ, Baskin DG.

Article CAS PubMed Google Scholar Shai I, Schwarzfuchs D, Henkin Y, Shahar DR, Witkow S, Greenberg I, Golan R, Fraser D, Bolotin A, Vardi H, Tangi-Rozental O, Zuk-Ramot R, Sarusi B, Brickner D, Schwartz Z, Sheiner E, Marko R, Katorza E, Thiery J, Fiedler GM, Blüher M, Stumvoll M, Stampfer MJ, Dietary Intervention Randomized Controlled Trial DIRECT Group.

Article CAS PubMed Google Scholar Sharma AM, Kushner RF. Article PubMed Google Scholar Sjöström L, Peltonen M, Jacobson P, et al. Article PubMed Google Scholar Smith SR, Weissman NJ, Anderson CM, Behavioral Modifi cation and Lorcaserin for Overweight and Obesity Management BLOOM Study Group, et al.

Article CAS PubMed Google Scholar Spalding KL, Arner E, Westermark PO, Bernard S, Buchholz BA, Bergmann O, Blomqvist L, Hoffstedt J, Näslund E, Britton T, Concha H, Hassan M, Rydén M, Frisén J, Arner P. Article CAS PubMed Google Scholar Speliotes EK, Massaro JM, Hoffmann U, et al.

Article CAS PubMed Google Scholar Stumvoll M, Goldstein BJ, van Haeften TW. Article CAS PubMed Google Scholar Stunkard AJ, Foch TT, Hrubec Z.

Article CAS PubMed Google Scholar Stunkard AJ, Sorensen TI, Hanis C, Teasdale TW, Chakraborty R, Schull WJ, et al. Article CAS PubMed Google Scholar Swinburn BA, Sacks G, Hall KD, McPherson K, Finegood DT, Moodie ML, Gortmaker SL. Article PubMed Google Scholar Tack J, Deloose E.

Article CAS PubMed Google Scholar Tham JC, Howes N, le Roux CW. Article PubMed PubMed Central Google Scholar Thorne A, Lonnqvist F, Apelman J, Hellers G, Arner P.

Article CAS PubMed Google Scholar Torgerson JS, Hauptman J, Boldrin MN, Sjöström L. Article CAS PubMed Google Scholar Tran TT, Yamamoto Y, Gesta S, Kahn CR. Article CAS PubMed PubMed Central Google Scholar UKPDS.

Google Scholar Unick JL, Neiberg RH, Hogan PE, Look AHEAD Research Group, et al. Article Google Scholar van Marken Lichtenbelt WD, Vanhommerig JW, Smulders NM, Drossaerts JM, Kemerink GJ, Bouvy ND, Schrauwen P, Teule GJ. Article PubMed Google Scholar Waldén TB, Hansen IR, Timmons JA, Cannon B, Nedergaard J.

Article CAS PubMed Google Scholar Wardle J, Carnell S, Haworth CM, Plomin R. Article CAS PubMed Google Scholar Wei M, Kampert JB, Barlow CE, Nichaman MZ, Gibbons LW, Paffenbarger RS Jr, Blair SN. Article CAS PubMed Google Scholar Weisberg SP, McCann D, Desai M, Rosenbaum M, Leibel RL, Ferrante AW Jr.

Article CAS PubMed PubMed Central Google Scholar White MF. Article CAS PubMed Google Scholar WHO Expert Committee on Definition. Google Scholar WHO fact sheet. Article CAS PubMed Google Scholar Zhang Y, et al.

Article Google Scholar Download references. View author publications. Editor information Editors and Affiliations Division of Endocrinology, Diabetes and Metabolism, University and Hospital Trust of Verona, Verona, Italy Enzo Bonora Diabetes Division, Diabetes Research Unit, University of Texas Health Science Center, San Antonio, TX, USA Ralph A.

Rights and permissions Reprints and permissions. Copyright information © Springer Nature Switzerland AG. About this entry. Cite this entry Blüher, M. Copy to clipboard. Publish with us Policies and ethics. Diabetic ketoacidosis DKA. National Center for Complementary and Integrative Health.

Type 2 diabetes and dietary supplements: What the science says. Preventing diabetes problems. Schillie S, et al. Prevention of hepatitis B virus infection in the United States: Recommendations of the Advisory Committee on Immunization Practices. MMWR Recommendations and Reports.

Related Caffeine: Does it affect blood sugar? Diabetes prevention: 5 tips for taking control GLP-1 agonists: Diabetes drugs and weight loss Hyperinsulinemia: Is it diabetes?

Medications for type 2 diabetes Show more related content. Associated Procedures A1C test Bariatric surgery Endoscopic sleeve gastroplasty Gastric bypass Roux-en-Y Glucose tolerance test Show more associated procedures.

News from Mayo Clinic Mayo study uses electronic health record data to assess metformin failure risk, optimize care Feb. CDT Mayo Clinic Minute: Strategies to break the heart disease and diabetes link Nov. CDT Mayo Clinic Q and A: Diabetes risk in Hispanic people Oct.

CDT The importance of diagnosing, treating diabetes in the Hispanic population in the US Sept. CDT Mayo Clinic Minute: Managing Type 2 diabetes Sept. CDT Expert Alert: Mayo Clinic Healthcare cardiologist explains link between diabetes, heart disease March 23, , p.

CDT Show more news from Mayo Clinic. Mayo Clinic Press Check out these best-sellers and special offers on books and newsletters from Mayo Clinic Press. Mayo Clinic on Incontinence - Mayo Clinic Press Mayo Clinic on Incontinence The Essential Diabetes Book - Mayo Clinic Press The Essential Diabetes Book Mayo Clinic on Hearing and Balance - Mayo Clinic Press Mayo Clinic on Hearing and Balance FREE Mayo Clinic Diet Assessment - Mayo Clinic Press FREE Mayo Clinic Diet Assessment Mayo Clinic Health Letter - FREE book - Mayo Clinic Press Mayo Clinic Health Letter - FREE book.

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Excess sugar in the blood causes many health-related problems. The cells cannot get enough of the sugar they need, and when sugar levels in the blood become too high, it causes damage to nerves and blood vessels, usually in the heart, feet, hands, kidneys and eyes.

Other complications of high sugar and insulin resistance include:. Excess weight can greatly affect your health in many ways, with type 2 diabetes being one of the most serious. There are many forms of measurement used to evaluate someone's excess weight; however, the most commonly-used method is calculating your body mass index BMI.

BMI is a number calculated by dividing a person's weight in kilograms by his or her height in meters squared. BMI is a useful tool used in determining the degree of an individual's excess weight.

There are five weight status categories that you may fit into:. When an individual predisposed to diabetes has excess weight, the cells in the body become less sensitive to the insulin that is released from the pancreas. There is some evidence that fat cells are more resistant to insulin than muscle cells.

Individuals affected by type 2 diabetes who exercise appear to reduce the severity of insulin-resistance because the exercising muscles use the extra sugar found in the blood; therefore, the body does not secrete insulin and the sugar is no longer diverted to excess fat cells.

It's not just how much an individual weighs, but also where they carry the weight that puts them at greater risk for health problems.

Individuals carrying more weight around their waist apple-shaped are more likely to suffer from obesity-related conditions than someone who carries more weight in their hips and thighs pear-shaped.

Individuals affected by excess weight, particularly obesity and morbid obesity, are more likely to develop type 2 diabetes as a related condition of their excess weight. Obesity and morbid obesity greatly increase your risk of having heart disease, type 2 diabetes, certain types of cancer, sleep apnea, osteoarthritis and much more.

What you consume throughout your day and how active you are affects your risk of developing type 2 diabetes. Being overweight BMI of The more excess weight you have, the more resistant your muscle and tissue cells become to your own insulin hormone. In addition to excess weight, there are many other factors that increase your risk of developing type 2 diabetes, such as:.

Inactivity and being overweight go hand-in-hand with a diagnosis of type 2 diabetes. Muscle cells have more insulin receptors than fat cells, so an individual can decrease insulin resistance by exercising. Being more active also lowers blood sugar levels by helping insulin to be more effective.

Unhealthy eating is a contributor to obesity. Too much fat in your diet, not enough fiber and too many simple carbohydrates all contribute to the development of type 2 diabetes.

It appears that people who have family members with type 2 diabetes are at a greater risk for developing it themselves. Asians, Pacific Islanders, American Indians, Alaskans, African Americans and Hispanics all have a higher than normal rate of type 2 diabetes.

As we age, the risk of type 2 diabetes becomes greater. Even if an elderly person is thin, they still may be predisposed to developing diabetes.

The pancreas ages right along with us and doesn't pump insulin as efficiently as it did when we were younger. As our cells age, they become more resistant to insulin as well. These two factors are the hallmark risk factors for many diseases and conditions, including type 2 diabetes.

Not only do they damage heart vessels, but they are two key components in metabolic syndrome, a cluster of symptoms including obesity, a high fat diet and lack of exercise. Having metabolic syndrome increases the risk of heart disease, stroke and type 2 diabetes. Women affected by obesity are more insulin resistant when compared to women of normal weight.

There are a variety of blood tests that may indicate whether you have type 2 diabetes.

Epidemiology of Obesity in T1D

See "Classification of diabetes mellitus and genetic diabetic syndromes", section on 'Latent autoimmune diabetes in adults LADA '.

A population-based study of over patients with type 2 diabetes demonstrated that many patients have A1C levels higher than ideal for years owing to a delay in or absence of medication changes to improve glycemic management [ 12 ].

Adherence to algorithms that dictate changes in treatment at designated intervals and computerized decision aids may improve A1C more efficiently than standard care [ 14,16,17 ].

OUR APPROACH — The therapeutic options for patients who have deterioration of glycemic management on initial therapy with lifestyle intervention and metformin are to add a second oral or injectable agent, including addition of insulin as an option, or to switch to insulin table 2.

Our approach outlined below is largely consistent with American and European guidelines [ 1,2,18 ]. The guidelines emphasize the importance of individualizing the choice of medications for the treatment of diabetes, considering important comorbidities including cardiovascular disease [CVD], heart failure HF , diabetic kidney disease DKD , hypoglycemia risk, and need for weight loss and patient-specific factors including patient preferences, needs, values, and cost.

We also agree with the World Health Organization WHO guidelines that sulfonylureas have a long-term safety profile, are inexpensive, and are highly effective, especially when used as described below, with patient education and dose adjustment to minimize side effects [ 19 ].

Short-acting sulfonylureas are preferred to reduce the risk of hypoglycemia. Our selection of drugs described below is based upon clinical trial evidence and clinical experience in achieving glycemic targets, with the recognition that there are few high-quality, longer-term, head-to-head drug comparison trials, particularly trials examining clinically important health outcomes cardiovascular events, mortality in patients without existing or multiple risk factors for atherosclerotic CVD ASCVD.

In a network meta-analysis of trials evaluating the effects of selected metformin-based combinations on A1C, mortality, and vascular outcomes in a heterogeneous group of patients with variable cardiovascular risk, the greatest reduction in A1C was seen with the addition of glucagon-like peptide 1 GLP-1 receptor agonists, premixed insulin, basal-bolus insulin, basal insulin, or prandial insulin reductions in A1C ranging from For patients at low cardiovascular risk, all treatments were similar to placebo for vascular outcomes.

For patients at increased cardiovascular risk, oral semaglutide, empagliflozin , and liraglutide all compared with placebo reduced all-cause mortality and cardiovascular death odds ratios [ORs] ranging from 0.

Sodium-glucose co-transporter 2 SGLT2 inhibitors, in general, had favorable effects on hospitalization for HF and progression of renal disease. In other meta-analyses, metformin combination therapy decreased A1C levels more than metformin monotherapy by approximately 1 percentage point [ 21,22 ].

Most combinations similarly reduced A1C. Moderate evidence favored metformin plus a GLP-1 receptor agonist over metformin plus a dipeptidyl peptidase 4 DPP-4 inhibitor for reducing A1C levels [ 21 ].

As expected, the use of thiazolidinediones, sulfonylureas, and insulin was associated with weight gain, while metformin, GLP-1 receptor agonists, SGLT2 inhibitors, and DPP-4 inhibitors were associated with weight loss or weight maintenance.

Sulfonylureas were associated with higher rates of hypoglycemia. Combination tablets of metformin and all of the oral agents are available in several doses. For patients who are doing well on these particular doses, the combination tablets offer the convenience of taking fewer pills.

However, if the patient requires that the dose of either drug be changed independent of the other drug, then a fixed combination is unhelpful. In addition, the cost of the brand name combinations is substantially greater than the generic components individually.

Monotherapy failure — For patients with deterioration of glycemic management while taking initial oral monotherapy, many available medication classes can be used with metformin or in combination with each other if metformin is contraindicated or not tolerated.

Related Pathway s : Diabetes: Medication selection for non-pregnant adults with type 2 DM and persistent hyperglycemia despite monotherapy and Diabetes: Initiation and titration of insulin therapy in non-pregnant adults with type 2 DM.

Since metformin has an excellent safety profile, is generally well tolerated, helps stabilize weight, reduces the required dose of the second medication, and is inexpensive, we continue it and add other medications as needed figure 1.

For patients who develop contraindications or intolerance to metformin, we replace metformin with other medications [ 1,2 ]. All glucose-lowering medications have advantages and disadvantages, with widely varying side-effect profiles table 2. All of the newer medicines that are not available in generic form are relatively expensive.

For patients with persistent hyperglycemia while taking metformin mg per day or a lower maximally tolerated dose , the choice of a second medication should be individualized based on efficacy, risk for hypoglycemia, the patient's comorbid conditions, impact on weight, side effects, and cost.

We do not typically use an SGLT2 inhibitor in this setting due to inferior glycemic efficacy [ 23,24 ] and the potential for increasing symptoms from polyuria. Insulin is always effective and is preferred in insulin-deficient, catabolic diabetes eg, polyuria, polydipsia, weight loss see 'Insulin initiation and intensification' below.

While basal insulin has historically been the preferred medication to add to metformin when A1C is markedly elevated even in the absence of catabolic symptoms , GLP-1 receptor agonists are an effective alternative to basal insulin when type 1 diabetes is not likely.

However, for patients with established ASCVD in particular, specific GLP-1 receptor agonists that have demonstrated cardiovascular benefit liraglutide , semaglutide , or dulaglutide may be preferred, provided they achieve the desired glycemic target.

Gastrointestinal GI side effects and contraindications to GLP-1 receptor agonists, as well as cost, may limit their use. See "Glucagon-like peptide 1-based therapies for the treatment of type 2 diabetes mellitus", section on 'Cardiovascular effects' and "Glucagon-like peptide 1-based therapies for the treatment of type 2 diabetes mellitus", section on 'Adverse effects'.

However, longer-acting analogs are similar to NPH with regard to total or severe hypoglycemia and have the important disadvantage of higher cost.

These data are reviewed separately. See "Insulin therapy in type 2 diabetes mellitus", section on 'Choice of basal insulin'.

Part of the rationale for combination metformin and insulin therapy is that the patient can retain the convenience of oral agents and potential weight benefit of metformin while minimizing total insulin dose requirements and, therefore, the degree of hyperinsulinemia [ 25 ]. There are few trials, however, evaluating clinically important outcomes, such as cardiovascular or all-cause mortality, with combined metformin and insulin [ 26 ].

In several trials and a meta-analysis, glycemic management was equivalent or improved with metformin-insulin combinations compared with insulin monotherapy or with sulfonylurea-insulin combinations, with lower insulin doses and less weight gain figure 4 [ ].

In the United Kingdom Prospective Diabetes Study UKPDS , the combination of insulin with metformin was also associated with significantly less weight gain than twice-daily insulin injections or insulin combined with sulfonylureas [ 30 ].

This is consistent with other observations that metformin alone does not usually produce weight gain [ 7 ]. Combining insulin and sulfonylurea is usually not endorsed, as they have similar mechanisms of action providing more insulin , and the same glucose-lowering effect can usually be achieved with a modestly higher dose of insulin alone.

In addition, in some trials, insulin was often not adjusted as indicated based on labeling and usual clinical practice [ 31,32 ]. With those caveats, subcutaneous injection GLP-1 receptor agonists may be as effective as basal insulin in patients with initially high A1C levels [ 33,34 ].

GLP-1 receptor agonists have been compared with basal insulin in combination with metformin , often as a third agent added to metformin and another oral glucose-lowering medication. In most of these trials, GLP-1 receptor agonists have achieved at least equivalent glycemic management as the addition of basal insulin with the added benefit of weight loss, rather than weight gain, as is often seen with basal insulin.

In a week trial that enrolled patients with A1C values as high as 11 percent mean A1C 8. These trials are reviewed separately. See "Glucagon-like peptide 1-based therapies for the treatment of type 2 diabetes mellitus".

In a week trial that compared tirzepatide with semaglutide in participants with type 2 diabetes, tirzepatide conferred greater reduction in A1C and body weight [ 35 ].

Clinical data are not yet available to establish whether tirzepatide also provides the cardiovascular or kidney protective benefits shown for some GLP-1 receptor agonists. Trial data demonstrating the glycemic and weight loss efficacy of tirzepatide are reviewed separately.

See "Glucagon-like peptide 1-based therapies for the treatment of type 2 diabetes mellitus", section on 'Clinical outcomes'. Data from small trials demonstrate substantial inter-individual variability in treatment response to specific medications for endpoints including glycemia and reduction in albuminuria [ 36,37 ], further underscoring the importance of individualized therapy.

Established cardiovascular or kidney disease — For patients with existing ASCVD, HF, or albuminuric DKD, a glucose-lowering medication with evidence of cardiac or kidney benefit should be added to metformin algorithm 2. SGLT2 inhibitors with cardiovascular benefit empagliflozin or canagliflozin are good alternatives.

See "Glucagon-like peptide 1-based therapies for the treatment of type 2 diabetes mellitus", section on 'Cardiovascular effects'. In the setting of declining eGFR, the main reason to prescribe an SGLT2 inhibitor is to reduce progression of DKD.

However, cardiac and kidney benefits have been shown in patients with eGFR below this threshold. See "Treatment of diabetic kidney disease", section on 'Type 2 diabetes: Treat with additional kidney-protective therapy'. In the absence of randomized trials directly comparing cardiovascular outcomes of the GLP-1 receptor agonists and SGLT2 inhibitors, the following findings and those from network meta-analyses [ 38,39 ] largely support our approach outlined above:.

See "Sodium-glucose cotransporter 2 inhibitors for the treatment of hyperglycemia in type 2 diabetes mellitus", section on 'Cardiovascular effects'. Patients at high CVD risk but without a prior event might benefit, but the data are less definitive [ 45 ].

Similarly, patients without severely increased albuminuria derive some benefit, but the absolute benefits are greater among those with severely increased albuminuria. For the other primary outcome a composite of hospitalization for myocardial infarction or stroke , there was a small benefit with SGLT2 inhibitors in patients with a history of CVD rate difference There was no difference in CVD outcomes between the two classes in those without a history of CVD.

GLP-1 receptor agonists are an alternative since glycemic benefit is independent of kidney function. In addition, GLP-1 receptor agonists have been shown to slow the rate of decline in eGFR and prevent worsening of albuminuria, albeit to a lesser degree than SGLT2 inhibitors.

GLP-1 receptor agonists should be titrated slowly, with monitoring for GI side effects, which could precipitate dehydration and acute kidney injury AKI. See "Sodium-glucose cotransporter 2 inhibitors for the treatment of hyperglycemia in type 2 diabetes mellitus" and "Glucagon-like peptide 1-based therapies for the treatment of type 2 diabetes mellitus", section on 'Microvascular outcomes'.

We avoid use of SGLT2 inhibitors in patients with frequent genitourinary yeast infections or bacterial urinary tract infections, low bone density and high risk for falls and fractures, foot ulceration, and factors predisposing to diabetic ketoacidosis eg, pancreatic insufficiency, drug or alcohol use disorder because of increased risk for each while using these agents.

SGLT2 inhibitors should be held for procedures, colonoscopy preparation, and with poor oral intake to prevent diabetic ketoacidosis. See "Sodium-glucose cotransporter 2 inhibitors for the treatment of hyperglycemia in type 2 diabetes mellitus", section on 'Contraindications and precautions'.

In general, we tolerate higher glycemic targets, and, if medication is required, we prefer a short-acting, low-dose sulfonylurea eg, glipizide , repaglinide , linagliptin , or cautious use of a GLP-1 receptor agonist or insulin. See "Management of hyperglycemia in patients with type 2 diabetes and advanced chronic kidney disease or end-stage kidney disease", section on 'Treatment' and "Sulfonylureas and meglitinides in the treatment of type 2 diabetes mellitus", section on 'Use in chronic kidney disease' and "Sulfonylureas and meglitinides in the treatment of type 2 diabetes mellitus", section on 'Clinical use of meglitinides'.

Without established cardiovascular or kidney disease — For most patients without established ASCVD or kidney disease who have persistent hyperglycemia while taking metformin mg per day or a lower maximally tolerated dose , we suggest a GLP-1 receptor agonist or basal insulin based on the results of the GRADE trial, a comparative effectiveness study of commonly used classes of glucose lowering medications algorithm 2 [ 10,54 ].

In the GRADE trial, choice of a second glucose-lowering medication was evaluated in patients with type 2 diabetes A1C 6. Participants with hyperglycemia despite taking maximum tolerated doses of metformin were randomly assigned to treatment with U glargine, liraglutide , glimepiride , or sitagliptin.

Over a mean follow-up of five years, all four medications lowered A1C levels. The proportion of individuals with severe hypoglycemia was highest in the glimepiride group 2.

Liraglutide had the highest frequency of gastrointestinal side effects. The treatment groups did not differ in the rate of the prespecified secondary micro- or macrovascular outcomes, including moderately or severely increased albuminuria, reduced kidney function, peripheral neuropathy, major adverse cardiovascular events MACE , hospitalization for HF, cardiovascular mortality, or overall mortality [ 54,55 ].

However, there was a small reduction in the incidence of any CVD defined as first incidence of MACE, hospitalization for unstable angina or HF, or revascularization in any arterial bed with liraglutide 6. The GRADE trial was designed and implemented prior to the availability of SGLT2 inhibitors.

SGLT2 inhibitors have lower glycemic efficacy compared with basal insulin and GLP-1 receptor agonists [ 20 ].

The cardiovascular benefit of SGLT2 inhibitors has not been demonstrated in those at low cardiovascular risk. Shorter-term trial data also support selection of the dual-acting GLP-1 and GIP receptor agonist tirzepatide as a second glucose-lowering agent, particularly in individuals for whom substantial body weight loss is a treatment goal.

Trial data for tirzepatide are reviewed separately. The choice of an alternative glucose-lowering medication is guided by efficacy, patient comorbidities, preferences, side effects, and cost algorithm 2. These benefits are offset by risks of hypoglycemia and modest weight gain.

Sulfonylureas can be used safely and effectively with dose adjustment, even in people at risk of hypoglycemia, but this requires a bit more attention. We prefer a shorter-duration sulfonylurea or one with relatively lower risk for hypoglycemia eg, glipizide , glimepiride , since longer-acting glyburide is associated with a higher risk of hypoglycemia, especially in older or frail patients.

In addition, there are good data providing reassurance of the cardiovascular safety of these sulfonylureas. See "Sulfonylureas and meglitinides in the treatment of type 2 diabetes mellitus", section on 'Cardiovascular effects'.

The glycemic efficacy of sulfonylureas in combination with other oral agents is illustrated by the findings of a meta-analysis of trials in which sulfonylureas were added to oral agents predominantly metformin or thiazolidinediones [ 56 ].

Compared with placebo, the addition of sulfonylureas to oral diabetes treatment lowered A1C by 1. The clinical use, side effects, and concerns about the cardiovascular safety of sulfonylureas are reviewed separately.

See "Sulfonylureas and meglitinides in the treatment of type 2 diabetes mellitus". SGLT2 inhibitors are associated with modest weight loss. With both medication classes, weight loss effects are stronger when the medication is combined with sustained efforts at dietary modification.

In patients with diabetes mellitus and biopsy-proven NASH, pioglitazone has been shown to improve fibrosis as well as inflammation and steatosis. GLPbased therapies also appear to improve liver biopsy evidence of NASH.

These studies are reviewed in detail separately. See "Management of nonalcoholic fatty liver disease in adults", section on 'Patients with NASH and diabetes'. The potential benefits of these drugs must be balanced with their associated adverse effects.

In particular, pioglitazone is not typically a first-choice agent due to adverse effects, including increased risk of weight gain, fluid retention, HF, fractures, and the potential increased risk of bladder cancer.

It may play a role in the treatment of selected patients with severe insulin resistance, NASH or nonalcoholic fatty liver disease , at low risk of fracture.

Adverse effects of pioglitazone may be minimized by using 15 to 30 mg rather than the 45 mg highest dose. See "Management of nonalcoholic fatty liver disease in adults", section on 'Patients with NASH and diabetes' and "Thiazolidinediones in the treatment of type 2 diabetes mellitus", section on 'Safety' and "Glucagon-like peptide 1-based therapies for the treatment of type 2 diabetes mellitus", section on 'Adverse effects'.

Trials comparing other combinations are reviewed separately in the individual topics. See "Glucagon-like peptide 1-based therapies for the treatment of type 2 diabetes mellitus", section on 'Glycemic efficacy' and "Dipeptidyl peptidase 4 DPP-4 inhibitors for the treatment of type 2 diabetes mellitus", section on 'Glycemic efficacy' and "Sodium-glucose cotransporter 2 inhibitors for the treatment of hyperglycemia in type 2 diabetes mellitus", section on 'Glycemic efficacy'.

Dual agent failure — For patients who have deterioration of glycemic management on dual therapy, the options include:. Although guidelines suggest combining SGLT2 inhibitors and GLP-1 receptor agonists [ 1 ], we do not usually add an SGLT2 inhibitor to GLP-1 receptor agonist therapy for hyperglycemia alone given the absence of data showing additive cardiovascular and kidney benefit and increased patient burden cost, polypharmacy, adverse effects.

The choice of additional therapy should be individualized, as discussed above for patients with monotherapy failure, based on efficacy, glycemic target, risk of hypoglycemia, the patient's underlying comorbidities, impact on weight, side effects, and cost.

See 'Monotherapy failure' above. In patients on sulfonylureas and metformin who are starting insulin therapy, sulfonylureas are generally discontinued, while metformin is continued.

In patients on a DPP-4 inhibitor who are starting a GLP-1 receptor agonist or dual-acting GLP-1 and GIP receptor agonist, the DPP-4 inhibitor should be discontinued.

Insulin dose requirements can decrease precipitously with the addition of these medications, requiring patient education and close follow-up with insulin dose adjustment in the short term to reduce the risk of hypoglycemia.

See "Glucagon-like peptide 1-based therapies for the treatment of type 2 diabetes mellitus", section on 'Cardiovascular effects' and "Sodium-glucose cotransporter 2 inhibitors for the treatment of hyperglycemia in type 2 diabetes mellitus", section on 'Cardiovascular effects'. In a meta-analysis of randomized trials evaluating the addition of a third agent in patients inadequately managed with two agents predominantly metformin and a sulfonylurea or metformin and a thiazolidinedione , triple-agent combinations reduced A1C to a greater extent than two agents [ 58 ].

In trials lasting 52 to 54 weeks, the addition of thiazolidinediones, GLP-1 receptor agonists, or SGLT2 inhibitors to metformin and sulfonylurea reduced A1C to a similar extent, and tirzepatide imparted even greater A1C reduction.

However, these trials did not directly compare the third-line agents with each other. Moreover, only the GRADE study was of sufficient duration to determine long-term glycemic effects.

For patients who are not well managed on two oral agents, switching to insulin may be less expensive than adding a third oral or injectable agent, depending on which insulin and which third oral or injectable agent is selected.

Insulin initiation and intensification — If a decision has been made to add insulin to oral hypoglycemic therapy in patients with type 2 diabetes, a single daily dose of either insulin NPH or detemir given at bedtime or insulin glargine or degludec given in the morning or at bedtime is a reasonable initial regimen [ 1 ].

Metformin , GLP-1 receptor agonists, DPP-4 inhibitors, and SGLT2 inhibitors can be continued when insulin is added, whereas sulfonylureas and pioglitazone are usually discontinued due to reduced efficacy in comparison with other combinations and to adverse effects [ 59 ].

Patients should measure blood glucose at appropriate times, and usually once to twice per day, depending on the insulin used and timing of administration.

For example, if bedtime NPH is used, it should be adjusted based on fasting glucose levels. More frequent self-monitoring should be implemented during insulin dose adjustment and when changes in daily activities traveling, changes in diet or exercise pattern or acute illness makes insulin adjustments necessary.

The dose of basal or long-acting insulin may be adjusted every three to four days until fasting glucose targets are achieved. Once an insulin regimen is stable, less frequent glucose monitoring may suffice.

See "Insulin therapy in type 2 diabetes mellitus", section on 'Titrating dose'. Related Pathway s : Diabetes: Initiation and titration of insulin therapy in non-pregnant adults with type 2 DM.

For patients who continue to have poor glycemic management on basal insulin after titration, diet and exercise patterns should be reviewed. Potential next steps include adding rapid-acting insulin before the largest meal and then two or three meals if needed , adding a GLP-1 receptor agonist, or changing to premixed insulin twice daily figure 5.

Several premixed combinations of basal and prandial insulin or basal insulin and a GLP-1 receptor agonist are available. See "Insulin therapy in type 2 diabetes mellitus", section on 'Designing an insulin regimen' and "General principles of insulin therapy in diabetes mellitus" and "Glucagon-like peptide 1-based therapies for the treatment of type 2 diabetes mellitus".

Use of an intensive insulin regimen with multiple daily injections MDI; similar to that used in type 1 diabetes may be necessary in insulin-deficient type 2 diabetes. Patients with type 2 diabetes on MDI or with insulin deficiency may benefit from devices used more commonly in type 1 diabetes such as insulin pumps or continuous glucose monitors.

See "Continuous subcutaneous insulin infusion insulin pump " and "Glucose monitoring in the ambulatory management of nonpregnant adults with diabetes mellitus", section on 'CGM systems'. MDI results in higher serum insulin concentrations and better glycemic management than that achieved with either an oral drug or basal insulin therapy alone [ 7 ].

MDI in type 2 diabetes may require large doses of insulin to overcome insulin resistance and can be associated with substantial weight gain averaging 8. Patients with type 2 diabetes with generalized obesity or with central overweight, often with nonalcoholic fatty liver disease, frequently require insulin doses in the range of 65 to units per day or much higher.

Although the total daily dose of insulin may be high, the insulin dose per kilogram is less remarkable. High daily insulin requirements may prompt consideration of use of concentrated insulins, such as U glargine or U regular insulin.

Concentrated insulin formulations deliver more potent insulins in smaller volumes, which is less cumbersome for patients and facilitates improved insulin absorption. See "General principles of insulin therapy in diabetes mellitus", section on 'U regular insulin' and "General principles of insulin therapy in diabetes mellitus", section on 'Basal insulin analogs'.

While use of concentrated insulins is often effective for glycemic management, the worsening obesity associated with high-dose insulin can result in progressively increasing insulin requirements.

This phenomenon may then lead to reconsideration of addition of an insulin-sparing agent eg, GLP-1 receptor agonist or thiazolidinedione or bariatric surgery. See 'Bariatric metabolic surgery' below and "Medical nutrition therapy for type 2 diabetes mellitus".

The vast majority of these CVD safety studies were placebo-controlled and enrolled all or a majority of patients with pre-existing CVD or at high cardiovascular risk, representing a minority of the type 2 diabetes population.

The long-term benefits and risks of using one agent over another in the absence of diagnosed CVD or high atherosclerotic CVD ASCVD risk are less clear. Thus, the results of these trials are most applicable to patients similar to the trial population and not to all patients with type 2 diabetes [ 2,60 ].

Cardiovascular benefit has been demonstrated for some of these medications when taken in combination with metformin , but benefit has not been definitively established in drug-naïve patients at low to moderate cardiovascular risk.

See 'Without established cardiovascular or kidney disease' above. The cardiovascular effects of each diabetes drug when data are available is reviewed in the individual topics.

See "Metformin in the treatment of adults with type 2 diabetes mellitus", section on 'Cardiovascular effects' and "Sulfonylureas and meglitinides in the treatment of type 2 diabetes mellitus", section on 'Cardiovascular effects' and "Glucagon-like peptide 1-based therapies for the treatment of type 2 diabetes mellitus", section on 'Cardiovascular effects' and "Thiazolidinediones in the treatment of type 2 diabetes mellitus", section on 'Cardiovascular effects' and "Dipeptidyl peptidase 4 DPP-4 inhibitors for the treatment of type 2 diabetes mellitus", section on 'Cardiovascular effects' and "Sodium-glucose cotransporter 2 inhibitors for the treatment of hyperglycemia in type 2 diabetes mellitus", section on 'Cardiovascular effects' and "Insulin therapy in type 2 diabetes mellitus".

They can reduce A1C values slightly 0. They act predominantly by lowering glucose concentrations after meals but may be poorly tolerated because of flatulence and other gastrointestinal GI side effects.

However, if they are started at a low dose 25 mg before meals and slowly increased, they can be effective in people who follow high-carbohydrate diets.

See "Alpha-glucosidase inhibitors for treatment of diabetes mellitus". Pramlintide is only approved for use in patients also taking prandial insulin, and therefore, it is not generally used in patients with type 2 diabetes. It also has frequent GI side effects.

See "Amylin analogs for the treatment of diabetes mellitus". In , another inhaled insulin preparation was approved by the US Food and Drug Administration FDA.

Inhaled insulin causes a very rapid rise in serum insulin concentration similar to that after subcutaneous rapid-acting insulins and faster than that after subcutaneous regular insulin. It is designed to be used to manage postprandial glucose levels.

Inhaled insulin may cause a transient cough with each inhalation, and it requires pulmonary monitoring. It is used infrequently in patients with type 2 diabetes.

See "Inhaled insulin therapy in diabetes mellitus". Colesevelam's mechanism of action to improve glycemia is uncertain [ 64 ]. One possibility is that bile acid sequestrants act in the GI tract to reduce glucose absorption. In a meta-analysis of five short-term trials 16 to 26 weeks in patients with type 2 diabetes inadequately treated with oral agents or insulin, the addition of colesevelam compared with placebo modestly reduced A1C levels mean difference 0.

The meta-analysis was limited by the high or unclear risk of bias in the individual trials. Side effects can include constipation, nausea, and dyspepsia.

In contrast to its effects on LDL cholesterol, colesevelam increases triglyceride concentrations by approximately 20 percent [ 66,67 ]. The clinical implications of this increase are unknown. See "Lipoprotein classification, metabolism, and role in atherosclerosis", section on 'Apolipoprotein C-III'.

Given the modest glucose-lowering effectiveness, expense, and limited clinical experience, we typically do not recommend colesevelam to improve glycemic management in patients with type 2 diabetes. See "Management of hyperprolactinemia", section on 'Overview of dopamine agonists'.

A quick-release formulation of bromocriptine has been approved by the FDA for the treatment of type 2 diabetes mellitus [ 68 ].

In short-term clinical trials in patients with type 2 diabetes mellitus, bromocriptine up to 4. Common side effects include nausea, vomiting, dizziness, and headache [ 70 ].

The mechanism of action in reducing blood sugar is unknown. Given its modest glucose-lowering effect, very frequent GI side effects, and the availability of more effective drugs, we do not recommend bromocriptine for the treatment of type 2 diabetes.

BARIATRIC METABOLIC SURGERY — In patients with type 2 diabetes and obesity, bariatric and metabolic surgical procedures that result in sustained, major weight loss have been shown to lead to at least temporary remission of diabetes in a substantial fraction of patients. Bariatric surgical procedures are targeted at weight loss in the setting of obesity; the term "metabolic surgery" is used when a major goal of surgery is to improve diabetes or other metabolic diseases eg, nonalcoholic fatty liver disease.

Patient selection — Surgical treatment of obesity is an option to treat type 2 diabetes in appropriate surgical candidates with [ 71 ]:. Surgical treatment has also been endorsed in patients with type 2 diabetes with BMI 30 to Given the increasing availability of potent GLPbased therapies and lack of comparative effectiveness data for bariatric surgery and these potent agents, we review these options with our patients and engage in shared decision-making.

See "Initial management of hyperglycemia in adults with type 2 diabetes mellitus", section on 'Diabetes education' and "Bariatric surgery for management of obesity: Indications and preoperative preparation", section on 'Indications'.

Outcomes — Unblinded trials have compared bariatric surgery with medical therapy for the treatment of type 2 diabetes see "Outcomes of bariatric surgery", section on 'Diabetes mellitus'.

However, relapse of diabetes usually occurs over time, with 35 to 50 percent of patients who initially achieved diabetes remission after surgery experiencing a recurrence [ 72,75 ].

Nevertheless, bariatric surgery improves glycemia substantially and significantly more than medication therapy, and most patients have marked improvement in glycemic management for at least 5 to 15 years after surgery. The effects of bariatric surgery on diabetes-related complications are reviewed in detail elsewhere.

See "Outcomes of bariatric surgery", section on 'Diabetic complications'. Risks and concerns — Despite these impressive metabolic results, concerns remain about acute postoperative complications including the need for reoperations and rehospitalizations and rare, but potentially severe, adverse events; the long-term success rates in maintaining weight loss [ 71,80,81 ]; and the reproducibility of the results in patients with an extensive history of diabetes or with different surgical teams [ 82 ].

Some weight regain is typical within two to three years of bariatric procedures, and different procedures result in different levels of weight loss and corresponding reductions in glycemia.

Bariatric surgical procedures are reviewed in detail elsewhere. See "Bariatric procedures for the management of severe obesity: Descriptions" and "Bariatric surgery for management of obesity: Indications and preoperative preparation" and "Bariatric operations: Early fewer than 30 days morbidity and mortality".

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. See "Society guideline links: Diabetes mellitus in adults" and "Society guideline links: Diabetes mellitus in children" and "Society guideline links: Diabetic kidney disease".

These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10 th to 12 th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword s of interest.

This decision is based on glycated hemoglobin A1C assay results calculator 1 typically performed every three to six months after initial therapy. After a successful initial response to lifestyle intervention and oral therapy, the majority of patients do not maintain target A1C levels during the subsequent three to five years.

See 'Indications for a second agent' above. Options include glucagon-like peptide 1 GLP-1 receptor agonists, a dual-acting GLP-1 and glucose-dependent insulinotropic polypeptide GIP receptor agonist tirzepatide , sodium-glucose co-transporter 2 SGLT2 inhibitors, short-acting sulfonylureas eg, glipizide , glimepiride , repaglinide if sulfonylurea not chosen as initial therapy , insulin, dipeptidyl peptidase 4 DPP-4 inhibitors, and pioglitazone figure 1 and table 2.

For patients with persistent hyperglycemia while taking a maximally tolerated dose of metformin, the choice of a second medication should be individualized based on efficacy, risk for hypoglycemia, the patient's comorbid conditions, impact on weight, side effects, and cost.

These agents have been shown to have the best glycemic efficacy algorithm 1. Gastrointestinal GI side effects, contraindications, and cost may limit their use. To select a medication, we use shared decision-making with a focus on beneficial and adverse effects within the context of the degree of hyperglycemia as well as a patient's comorbidities and preferences algorithm 2.

See 'Established cardiovascular or kidney disease' above. The majority of patients in the cardiovascular and renal outcomes trials had established cardiovascular disease CVD or diabetic kidney disease DKD with severely increased albuminuria, and therefore, these are the primary indications for one of these drugs.

Patients at high CVD risk but without a prior event might benefit, but the data are less supportive. Similarly, patients without severely increased albuminuria have some benefit, but the absolute benefits are greater among those with severely increased albuminuria.

The choice of an alternative glucose-lowering medication is guided by efficacy, patient comorbidities, preferences, side effects, and cost. algorithm 2. See 'Dual agent failure' above. For most patients who do not achieve target A1C with initial dual therapy, we suggest starting insulin or a GLP-1 receptor agonist Grade 2B if neither already chosen as a second agent.

In patients on sulfonylureas and metformin who are starting insulin therapy, sulfonylureas are generally tapered and discontinued, while metformin is continued.

In patients on DPP-4 inhibitors who are starting a GLP-1 receptor agonist or dual-acting GLP-1 and GIP receptor agonist, the DPP-4 inhibitor is discontinued, while metformin is continued. See 'Dual agent failure' above and 'Insulin initiation and intensification' above.

Related Pathway s : Diabetes: Initial therapy for non-pregnant adults with type 2 DM. An alternative is two oral agents and a GLP-1 receptor agonist or dual-acting GLP-1 and GIP receptor agonist, particularly for patients in whom weight loss or avoidance of hypoglycemia is a primary consideration.

These GLPbased therapies should not be combined with DPP-4 inhibitors. In addition to excess weight, there are many other factors that increase your risk of developing type 2 diabetes, such as:. Inactivity and being overweight go hand-in-hand with a diagnosis of type 2 diabetes.

Muscle cells have more insulin receptors than fat cells, so an individual can decrease insulin resistance by exercising. Being more active also lowers blood sugar levels by helping insulin to be more effective. Unhealthy eating is a contributor to obesity. Too much fat in your diet, not enough fiber and too many simple carbohydrates all contribute to the development of type 2 diabetes.

It appears that people who have family members with type 2 diabetes are at a greater risk for developing it themselves.

Asians, Pacific Islanders, American Indians, Alaskans, African Americans and Hispanics all have a higher than normal rate of type 2 diabetes. As we age, the risk of type 2 diabetes becomes greater. Even if an elderly person is thin, they still may be predisposed to developing diabetes.

The pancreas ages right along with us and doesn't pump insulin as efficiently as it did when we were younger. As our cells age, they become more resistant to insulin as well. These two factors are the hallmark risk factors for many diseases and conditions, including type 2 diabetes.

Not only do they damage heart vessels, but they are two key components in metabolic syndrome, a cluster of symptoms including obesity, a high fat diet and lack of exercise. Having metabolic syndrome increases the risk of heart disease, stroke and type 2 diabetes.

Women affected by obesity are more insulin resistant when compared to women of normal weight. There are a variety of blood tests that may indicate whether you have type 2 diabetes. Let's take a look at each test and see what different results could mean for you and your health.

The amount of sugar in your blood naturally fluctuates but stays within a normal range. The preferred way to test your blood sugar is after you've fasted overnight for at least eight hours. A fasting blood sugar level less than milligrams of sugar per deciliter of blood is considered normal.

If your blood sugar level measures from to , you have impaired fasting glucose, and this may be an indication that you have pre-diabetes.

This test is done without any special preparation, such as fasting overnight. If it is and you also have symptoms of type 2 diabetes, you can expect a diagnosis of type 2 diabetes. This test requires you to visit a lab or a healthcare professional after at least an eight-hour fast.

At the office or lab, you will drink about eight ounces of a sweet liquid that contains a lot of sugar about 75 grams. Your blood sugar level will be measured before you drink the liquid, then after one hour and again after two hours.

Losing weight is one of the most beneficial ways you can help prevent type 2 diabetes. For many individuals, simply adjusting their caloric intake and beginning an exercise program can greatly improve their type 2 diabetes and overall health. Weight loss occurs when energy expenditure exceeds energy intake.

Creating a calorie deficit will result in weight loss. Writing down the food, portion size and calorie amount in a food diary will help you become aware of the foods you consume and provide objective evidence of calorie intake. Regular exercise helps maintain weight loss and prevent weight regain.

It also improves insulin sensitivity and glycemic control measurement of the effects of carbohydrates on blood sugar level and may decrease the risk of developing type 2 diabetes.

A goal should be set for 30 to 45 minutes of moderate exercise five times per week. The exercise does not need to occur in a single session to be beneficial. Dividing the activity into multiple and short episodes produces similar benefits and can enhance compliance.

The Obesity Action Coalition OAC is the only nonprofit organization whose sole purpose is representing those affected by obesity. The OAC offers many valuable educational resources discussing excess weight, obesity, morbid obesity, type 2 diabetes and much more. To see if you are at risk for type 2 diabetes, please schedule a visit with a healthcare professional for more information.

To help you prepare for your visit, we've provided you with some great sample questions that you may be asked by a healthcare professional and sample questions for you to ask a healthcare professional. Breadcrumb Home Medical services Weight loss and bariatric surgery Patient education and support Understanding excess weight and its role in type 2 diabetes.

Understanding excess weight and its role in type 2 diabetes. What is type 2 diabetes? What are the complications of high blood sugar levels? Other complications of high sugar and insulin resistance include: Increased risk of heart disease and stroke Neuropathy nerve damage, especially in extremities Nephropathy renal impairment, kidney failure Retinopathy vision problems, blindness Cardiovascular disease heart disease and increased risk of stroke Erectile dysfunction in men and decreased sexual desire in both men and women Depression Amputation How does excess weight impact type 2 diabetes?

There are five weight status categories that you may fit into: Underweight Normal weight Overweight Obese Morbidly obese When an individual predisposed to diabetes has excess weight, the cells in the body become less sensitive to the insulin that is released from the pancreas.

Are you at risk for type 2 diabetes? In addition to excess weight, there are many other factors that increase your risk of developing type 2 diabetes, such as: Sedentary lifestyle Inactivity and being overweight go hand-in-hand with a diagnosis of type 2 diabetes.

Unhealthy eating habits Unhealthy eating is a contributor to obesity. Family history and genetics It appears that people who have family members with type 2 diabetes are at a greater risk for developing it themselves. Increased age As we age, the risk of type 2 diabetes becomes greater.

High blood pressure and high cholesterol These two factors are the hallmark risk factors for many diseases and conditions, including type 2 diabetes.

Diabetes and Obesity Marsh BJ, Soden C, Alarcón C, Wicksteed BL, Yaekura K, Costin AJ, et al. Qaseem A, Barry MJ, Humphrey LL, et al. Rights and permissions Reprints and permissions. Smith, MD Steven R. T1D is characterized by a total or near lack of insulin secretion due to the destruction of β -cells by autoimmune or rarely other processes. The functional importance of adipose tissue for obesity, T1D, and T2D, described elsewhere in this review, includes its roles in metabolic flexibility, β -cell physiology, and mitochondrial function. Do you have diabetes educators available?
Buying options There was Chronic hyperglycemia and obesity difference in CVD outcomes between the two obesoty in those Hyperglydemia a history of CVD. Surwit RS, van Tilburg MA, Zucker N, et al. See 'Monitoring' above. Felig P, Marliss E, Cahill GF Jr. View in.
The prevalence Chronic hyperglycemia and obesity hypeerglycemia and diabetes Chronic hyperglycemia and obesity reached epidemic proportions Cheonic and contributes to premature mortality. Obesity increases the risk hhperglycemia metabolic and cardiovascular diseases, musculoskeletal disorders, Chronic hyperglycemia and obesity types of cancer, pulmonary diseases, and psychological diseases. A Sweet potato fries of the obesity hyperglcemia since the s may be caused by a globally increased intake of energy-dense foods with a parallel decrease in daily physical activity due to the increasingly sedentary nature of many forms of work, changing modes of transportation, and increasing urbanization. Obesity represents the strongest modifiable risk factor for type 2 diabetes T2D. Obesity and T2D may develop on a common genetic risk background. Mechanisms linking obesity to T2D include abdominal fat distribution, adipose tissue dysfunction, and inflammation characterized by the secretion of a diabetogenic adipokine pattern which contributes to impaired insulin action in skeletal muscle, liver, brain, and other organs.

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