Methods:

The study authors searched Embase, PubMed, Cochrane Library, and clinicaltrials.gov between December 1, 2008, and November 24, 2017, for randomized placebo-controlled trials. Studies were considered eligible for inclusion if they: 1) were randomized, placebo-controlled trials conducted in adults with T2DM; 2) compared add-on therapy of any current antidiabetic medication to placebo; and 3) reported incidence of HF or hospitalization for HF as a primary or secondary outcome. Exclusion criteria were as follows: observational and retrospective studies, studies completed before Food and Drug Administration (FDA) guidance, and studies that did not report HF as an outcome. Nine trials fulfilled the inclusion criteria, providing data on 87,162 participants. As per the inclusion criteria, they were placebo-controlled trials that evaluated the following classes of antidiabetic medication: GLP-1 agonists (four studies evaluating lixisenatide, liraglutide, semaglutide, and once-weekly exenatide, respectively, in 33,457 participants), DPP-4 inhibitors (three studies evaluating alogliptin, saxagliptin, and sitagliptin, respectively, in 36,543 participants), and SGLT-2 inhibitors (two studies evaluating empagliflozin and canagliflozin in 17,162 participants). The authors 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.