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Novel Anti-glycemic Drugs and Reduction of Cardiovascular Risk in Diabetes: Expectations Realized, Promises Unmet.

ABSTRACT: The purpose is to review evidence on cardiovascular risks and benefits of new treatments for type 2 diabetes mellitus.In response to guidance issued by the Food and Drug Administration, thousands of patients have been enrolled in large randomized trials evaluating the cardiovascular effects of the three newest diabetes drug classes: glucagon-like peptide-1 (GLP-1) receptor agonists, sodium glucose cotransporter 2 (SGLT-2) inhibitors, and dipeptidyl peptidase-4 (DPP-4) inhibitors. Two studies of GLP-1 receptor agonists-one of liraglutide and one of semaglutide-have shown cardiovascular benefit relative to placebo, and one study of the SGLT-2 inhibitor empagliflozin has shown benefit. The other published cardiovascular outcome studies of the newest drug classes have generally supported safety, apart from an as-yet unresolved safety concern about increased rates of heart failure with DPP-4 inhibitors. Recent research suggests the thiazolidinedione pioglitazone may have beneficial effects on some cardiovascular outcomes as well, but these are counterbalanced by a known increase of the risk of heart failure with this drug. In general, more prospective randomized trial data is now available regarding the cardiovascular effects of the newer diabetes drugs than on the older drug classes. New evidence suggests that the newest diabetes drugs are safe from a cardiovascular perspective. Evidence on benefit from at least some members of the GLP-1 receptor agonist and SGLT-2 inhibitor classes is encouraging but not yet decisive.

SUBMITTER: Flory JH

PROVIDER: S-EPMC5509052 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature

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Novel Anti-glycemic Drugs and Reduction of Cardiovascular Risk in Diabetes: Expectations Realized, Promises Unmet.

Flory James H JH Ukena Jenny K JK Floyd James S JS

Current atherosclerosis reports 20161201 12

<h4>Purpose of review</h4>The purpose is to review evidence on cardiovascular risks and benefits of new treatments for type 2 diabetes mellitus.<h4>Recent findings</h4>In response to guidance issued by the Food and Drug Administration, thousands of patients have been enrolled in large randomized trials evaluating the cardiovascular effects of the three newest diabetes drug classes: glucagon-like peptide-1 (GLP-1) receptor agonists, sodium glucose cotransporter 2 (SGLT-2) inhibitors, and dipeptid ...[more]

PMID: 27817160

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Project description:The prevalence of diabetes mellitus (DM) is steadily rising in the U.S., both in the general population and among those with cardiovascular disease (CVD). Understanding how to treat a patient with both conditions is becoming increasingly important. With multiple therapeutic options for CVD management, some medications will invariably impact glycemia in this group of patients. The concept of "DM-friendly" management of CVD is based on a treatment approach of selecting medications that do not impair glycemic control and provide equivalent cardioprotective effects. This article reviews the glycemic effects of various classes of medications commonly used to treat CVD.Data sources were all PubMed- and Google Scholar-referenced articles in English-language peer-reviewed journals from 1980 through April 2016. Studies selected could include observational studies or prospective clinical trials. Prospective clinical trials included in this review focused on investigating the association of the medication of interest with glycemic outcomes. Meta-analyses and systematic reviews were also included.The data on glycemic effects were lacking for many of the medication classes and individual medications examined. However, in our review, certain beta-blockers and renin angiotensin aldosterone system inhibitors, and select calcium channel blockers were consistently shown to have favorable glycometabolic profiles when compared with other commonly used cardiovascular therapies.Several commonly prescribed medications for the treatment of CVD, such as certain beta-blockers and renin angiotensin aldosterone system inhibiting agents, are associated with favorable glycometabolic effects. As clinicians are more often faced with the challenge of treating patients with DM and concomitant CVD, consideration of how common cardiovascular medications may affect glycemia should be incorporated into the clinical decision making process.A1C = hemoglobin A1C ACE = angiotensin-converting enzyme ARB = angiotensin II receptor blocker CCB = calcium channel blocker CI = confidence interval CVD = cardiovascular disease DM = diabetes mellitus MI = myocardial infarction RR = relative risk.

Project description:BackgroundThe comparative effectiveness of glucose-lowering medications for use with metformin to maintain target glycated hemoglobin levels in persons with type 2 diabetes is uncertain.MethodsIn this trial involving participants with type 2 diabetes of less than 10 years' duration who were receiving metformin and had glycated hemoglobin levels of 6.8 to 8.5%, we compared the effectiveness of four commonly used glucose-lowering medications. We randomly assigned participants to receive insulin glargine U-100 (hereafter, glargine), the sulfonylurea glimepiride, the glucagon-like peptide-1 receptor agonist liraglutide, or sitagliptin, a dipeptidyl peptidase 4 inhibitor. The primary metabolic outcome was a glycated hemoglobin level, measured quarterly, of 7.0% or higher that was subsequently confirmed, and the secondary metabolic outcome was a confirmed glycated hemoglobin level greater than 7.5%.ResultsA total of 5047 participants (19.8% Black and 18.6% Hispanic or Latinx) who had received metformin for type 2 diabetes were followed for a mean of 5.0 years. The cumulative incidence of a glycated hemoglobin level of 7.0% or higher (the primary metabolic outcome) differed significantly among the four groups (P<0.001 for a global test of differences across groups); the rates with glargine (26.5 per 100 participant-years) and liraglutide (26.1) were similar and lower than those with glimepiride (30.4) and sitagliptin (38.1). The differences among the groups with respect to a glycated hemoglobin level greater than 7.5% (the secondary outcome) paralleled those of the primary outcome. There were no material differences with respect to the primary outcome across prespecified subgroups defined according to sex, age, or race or ethnic group; however, among participants with higher baseline glycated hemoglobin levels there appeared to be an even greater benefit with glargine, liraglutide, and glimepiride than with sitagliptin. Severe hypoglycemia was rare but significantly more frequent with glimepiride (in 2.2% of the participants) than with glargine (1.3%), liraglutide (1.0%), or sitagliptin (0.7%). Participants who received liraglutide reported more frequent gastrointestinal side effects and lost more weight than those in the other treatment groups.ConclusionsAll four medications, when added to metformin, decreased glycated hemoglobin levels. However, glargine and liraglutide were significantly, albeit modestly, more effective in achieving and maintaining target glycated hemoglobin levels. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases and others; GRADE ClinicalTrials.gov number, NCT01794143.).

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Novel Anti-glycemic Drugs and Reduction of Cardiovascular Risk in Diabetes: Expectations Realized, Promises Unmet.

Publications

Novel Anti-glycemic Drugs and Reduction of Cardiovascular Risk in Diabetes: Expectations Realized, Promises Unmet.

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