Comparison of New Glucose-Lowering Drugs on Risk of Heart Failure in Type 2 Diabetes: A Network Meta-Analysis

Abstract

Objectives: The authors conducted a systematic review and network meta-analysis of placebo-controlled, randomized clinical trials in the post-Food and Drug Administration (FDA) guidance era to formally compare the effects of 3 new classes of glucose-lowering drugs on hospitalization for heart failure (HF) in type 2 diabetes mellitus.

Background: The 2008 FDA Guidance for Industry launched an era of cardiovascular outcome trials for new glucose-lowering drugs in T2DM, including glucagon-like peptide (GLP)-1 agonists, dipeptidyl peptidase (DPP)-4 inhibitors, and sodium glucose co-transporter (SGLT)-2 inhibitors.

Methods: We searched Embase, PubMed, Cochrane Library, and clinicaltrials.gov between December 1, 2008, and November 24, 2017, for randomized placebo-controlled trials, and performed network meta-analyses by Bayesian approach using Markov-chain Monte Carlo simulation method to compare the effects of glucose-lowering drugs on risk of HF hospitalization and estimate the probability that each treatment is the most effective.

Results: Nine studies were identified, yielding data on 87,162 participants. In the network meta-analysis, SGLT-2 inhibitors yielded the greatest risk reduction for HF hospitalization compared with placebo (relative risk [RR]: 0.56; 95% CrI [credibility interval]: 0.43 to 0.72). Moreover, SGLT-2 inhibitors were associated with significant risk reduction in pairwise comparisons with both GLP-1 agonists (RR: 0.59; 95% CrI: 0.43 to 0.79) and DPP-4 inhibitors (RR: 0.50; 95% CrI: 0.36 to 0.70). Ranking of the classes revealed 99.6% probability of SGLT-2 inhibitors being the optimal treatment for reducing the risk of this outcome, followed by GLP-1 agonists (0.27%) and DPP-4 inhibitors (0.1%).

Conclusions: Current evidence suggests that SGLT-2 inhibitors are more effective than either GLP-1 agonists or DPP-4 inhibitors for reducing the risk of hospitalization for HF in type 2 diabetes mellitus.

Keywords: dipeptidyl peptidase-4 inhibitor; glucagon-like peptide-1 agonist; heart failure; sodium glucose co-transporter-2 inhibitor; type 2 diabetes.