Clinical Question

Do newer (incretin-based) treatments for type 2 diabetes mellitus increase mortality?

Bottom Line

This seems like a strange question considering that the goal is to decrease mortality with drug therapy. Nevertheless, this study showed that the new kids on the diabetes block—exenatide (Byetta), dulaglutide (Trulicity), sitagliptin (Januvia), saxagliptin (Onglyza), and others—do not increase mortality, even in patients with cardiovascular risk. This jury is still out as to whether these agents do what they are supposed to do: decrease mortality as well as blood glucose levels. (Level of Evidence = 1a)

Synopsis

These researchers searched four databases, including Cochrane Central and clinicaltrials.gov, to identify randomized controlled trials that evaluated glucagon-like peptide-1 receptor agonists or dipeptidyl-peptidase-4 inhibitors with placebo or active treatment in patients with type 2 diabetes, including a large number of patients with cardiovascular disease. They included 112 studies in which at least one patient died. The studies comprised 151,614 total patients and ranged from 12 to 234 weeks in duration (median 24 weeks). Two researchers independently selected studies for inclusion and evaluated the research for bias, which was generally low. There was no difference in all-cause mortality between incretin drugs vs. control agents (odds ratio = 0.96; 95% confidence interval, 0.90 to 1.02). There was also no increased mortality in patients at risk of cardiovascular disease. There was little heterogeneity among the studies and no evidence of publication bias.

Study design: Meta-analysis (randomized controlled trials)

Funding source: Foundation

Setting: Various (meta-analysis)

Reference:LiuJLiLDengKet alIncretin based treatments and mortality in patients with type 2 diabetes: systematic review and meta-analysis. BMJ2017;357:j2499.