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Cardiovascular outcomes and safety with antidiabetic drugs.

ABSTRACT: Type 2 diabetes is a debilitating disease that impacts the life expectancy, quality of life, and health of an individual. Cardiovascular disease (CVD) is a common diabetes-associated complication and a principal cause for death in diabetic patients. This review aims to investigate and summarize the effect of Type 2 diabetes mellitus (T2DM) medications on CVD issues. A comprehensive literature review mainly from level 1 evidence was performed. Thirty-seven articles were extracted from Google Scholar, ScienceDirect, ProQuest, and PubMed Database using a combination of keywords. The findings suggest that different glucose-lowering agents have been tested for their efficacy and safety in T2DM with CVD. Some of the recent trials such as the "United Kingdom Prospective Diabetes Study," "Empagliflozin (EMPA) Cardiovascular (CV) Outcome Event Trial in T2DM Patients-Removing Excess Glucose" (EMPA-REG OUTCOME), "Liraglutide Effect and Action in Diabetes: Evaluation of CV Outcome Results," and "Trial to Evaluate CV and Other Long-term Outcomes with Semaglutide in Subjects with Type 2 Diabetes" (SUSTAIN6) have shed important light on this vital clinical concern, thus demonstrating a convincing effect of liraglutide, semaglutide, and EMPA on CVD outcomes, while metformin is thought to be the first-line optimal oral agent to manage Type 2 diabetics. Some classes of drugs demonstrate CV protection, some of them may be a result of a class effect, and some differences might be based on the population enrolled individually. Most of the trials failed to show a significant benefit with regard to mortality and morbidity in spite of intensive glycemic control. This study, therefore, enabled us to develop a guide of potential antidiabetic medication that can influence or promote CV health. Health professionals in future should weigh the CV risk against possible advantages while prescribing antidiabetic medications.

SUBMITTER: Aldossari KK

PROVIDER: S-EPMC6124835 | biostudies-other | 2018 Sep-Oct

REPOSITORIES: biostudies-other

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Cardiovascular outcomes and safety with antidiabetic drugs.

Aldossari Khaled K KK

International journal of health sciences 20180901 5

Type 2 diabetes is a debilitating disease that impacts the life expectancy, quality of life, and health of an individual. Cardiovascular disease (CVD) is a common diabetes-associated complication and a principal cause for death in diabetic patients. This review aims to investigate and summarize the effect of Type 2 diabetes mellitus (T2DM) medications on CVD issues. A comprehensive literature review mainly from level 1 evidence was performed. Thirty-seven articles were extracted from Google Scho ...[more]

PMID: 30202411

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Project description:OBJECTIVE:To evaluate the cardiovascular safety of canagliflozin, a sodium-glucose cotransporter 2 inhibitor for the treatment of type 2 diabetes mellitus, in direct comparisons with DPP-4 inhibitors (DPP-4i), GLP-1 receptor agonists (GLP-1RA), or sulfonylureas, as used in routine practice. DESIGN:Population based retrospective cohort study. SETTING:Nationwide sample of patients with type 2 diabetes from a large de-identified US commercial healthcare database (Optum Clinformatics Datamart). PARTICIPANTS:Three pairwise 1:1 propensity score matched cohorts of patients with type 2 diabetes 18 years and older who initiated canagliflozin or a comparator non-gliflozin antidiabetic agent (ie, a DPP-4i, a GLP-1RA, or a sulfonylurea) between April 2013 and September 2015. MAIN OUTCOME MEASURES:The primary outcomes were heart failure admission to hospital and a composite cardiovascular endpoint (comprised of being admitted to hospital for acute myocardial infarction, ischemic stroke, or hemorrhagic stroke). Hazard ratios and 95% confidence intervals were estimated in each propensity score matched cohort controlling for more than 100 baseline characteristics. RESULTS:During a 30 month period, the hazard ratio for heart failure admission to hospital associated with canagliflozin was 0.70 (95% confidence interval 0.54 to 0.92) versus a DPP-4i (n=17 667 pairs), 0.61 (0.47 to 0.78) versus a GLP-1RA (20 539), and 0.51 (0.38 to 0.67) versus a sulfonylurea (17 354 ). The hazard ratio for the composite cardiovascular endpoint associated with canagliflozin was 0.89 (0.68 to 1.17) versus a DPP-4i, 1.03 (0.79 to 1.35) versus a GLP-1RA, and 0.86 (0.65 to 1.13) versus a sulfonylurea. Results were similar in sensitivity analyses further adjusting for baseline hemoglobin A1c levels and in subgroups of patients with and without prior cardiovascular disease or heart failure. CONCLUSIONS:In this large cohort study, canagliflozin was associated with a lower risk of heart failure admission to hospital and with a similar risk of myocardial infarction or stroke in direct comparisons with three different classes of non-gliflozin diabetes treatment alternatives as used in routine care.

Project description:BackgroundRecent trials suggested that glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and sodium-glucose co-transporter-2 (SGLT-2) inhibitors reduced cardiovascular events. Comparative effectiveness of these new antidiabetic drug classes remains unclear. We therefore performed a network meta-analysis to compare the effect on cardiovascular outcomes among GLP-1 RAs, SGLT-2 and dipeptidyl peptidase-4 (DPP-4) inhibitors.MethodsMEDLINE, EMBASE, Cochrane database, ClinicalTrials.gov, and congress proceedings from recent cardiology conferences were searched up to April 20, 2019. Cardiovascular outcome trials and renal outcome trials reporting cardiovascular outcomes on GLP-1 RAs, SGLT-2 and DPP-4 inhibitors in patients with type 2 diabetes mellitus were included. The primary outcome was major adverse cardiovascular events (MACE). Secondary outcomes were nonfatal myocardial infarction, nonfatal stroke, cardiovascular mortality, all-cause mortality, hospitalisation for heart failure (HF), and renal composite outcome. ORs and 95% CI were calculated using random-effects models.ResultsFourteen trials enrolling 121,047 patients were included. SGLT-2 inhibitors reduced cardiovascular deaths and all-cause deaths compared to placebo (OR 0.82, 95% CI 0.73-0.93 and OR 0.84, 95% CI 0.77-0.92) and DPP-4 inhibitors (OR 0.83, 95% CI 0.70-0.99 and OR 0.83, 95% CI 0.73-0.94), respectively. SGLT-2 inhibitors and GLP-1 RAs significantly reduced MACE (OR 0.88, 95% CI 0.82-0.95 and OR 0.87, 95% CI 0.82-0.93), hospitalisation for HF (OR 0.68, 95% CI 0.61-0.77 and OR 0.87, 95% CI 0.82-0.93), and renal composite outcome (OR 0.59, 95% CI 0.52-0.67 and OR 0.86, 95% CI 0.78-0.94) compared to placebo, but SGLT-2 inhibitors reduced hospitalisation for HF (OR 0.79, 95% CI 0.69-0.90) and renal composite outcome (OR 0.69, 95% CI 0.59-0.80) more than GLP-1 RAs. Only GLP-1 RAs reduced nonfatal stroke (OR 0.88, 95% CI 0.77-0.99). DPP-4 inhibitors did not lower the risk of these outcomes when compared to placebo and were associated with higher risks of MACE, hospitalisation for HF, and renal composite outcome when compared to the other two drug classes.ConclusionsSGLT-2 inhibitors show clear superiority in reducing cardiovascular and all-cause deaths, hospitalisation for HF, and renal events among new antidiabetic drug classes. GLP-1 RAs also have cardiovascular and renal protective effects. DPP-4 inhibitors have no beneficial cardiovascular effects and are therefore inferior to the other two drug classes. SGLT-2 inhibitors should now be the preferred treatment for type 2 diabetes mellitus.

Project description:In the Guidance for Industry from the Food and Drug Administration in 2008, excess cardiovascular risk should be ruled out in trials of all new antidiabetic drugs; however, relatively few studies have focused on cardiovascular safety with antidiabetic drug use. We aimed to examine mortality and cardiovascular risk using a network meta-analysis. We searched the Medline, Embase, Cochrane, and ClinicalTrials.gov registry databases in March 2016 to identify randomized controlled trials reporting cardiovascular risk with the following oral antidiabetic drugs: metformin, sulfonylureas, thiazolidinedione (TZD), dipeptidyl peptidase-4 (DPP4) inhibitors, and sodium-glucose co-transporter-2 (SGLT2) inhibitors. We assessed the differences in the risks of all-cause mortality, cardiovascular-related mortality, acute coronary syndrome (ACS), and myocardial infarction (MI) among antidiabetic drugs with fixed effect models for direct pairwise comparisons and Bayesian network meta-analyses to integrate direct and indirect comparisons. Of the 101,183 patients in 73 randomized controlled trials, 3,434 (3.4%) died. The relative risks of all-cause mortality with SGLT2 inhibitor use were 0.68 (95% credible interval: 0.57-0.80), 0.74 (0.49-1.10), 0.63 (0.46-0.87), 0.71 (0.55-0.90), and 0.65 (0.54-0.78), compared with placebo, metformin, sulfonylurea, TZD, and DPP4 inhibitor, respectively. The relative risks of cardiovascular-related mortality with SGLT2 inhibitor use were 0.61 (0.50-0.76), 0.81(0.36-1.90), 0.52(0.31-0.88), 0.66(0.49-0.91), and 0.61(0.48-0.77), compared with placebo, metformin, sulfonylurea, TZD, and DPP4 inhibitor, respectively. The relative risks of ACS with SGLT2 inhibitor use was consistent with that of all-cause mortality. SGLT2 inhibitor use was associated with a lower risk of ACS than the other OADs and placebo. The relative risks of MI with SGLT2 inhibitor use were 0.77 (0.63-0.93) and 0.75 (0.60-0.94), compared with placebo and DPP4 inhibitor, respectively. The currently available data provide the evidence of cardiovascular benefit from use of SGLT2 inhibitors to patients with type 2 diabetes, although additional results from ongoing studies will be pivotal.

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Cardiovascular outcomes and safety with antidiabetic drugs.

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Cardiovascular outcomes and safety with antidiabetic drugs.

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