No increase in mortality with incretin-based drugs compared to other diabetes meds, review finds

The review included 189 randomized controlled trials that compared glucagon-like peptide-1 receptor agonists or dipeptidyl peptidase-2 inhibitors with placebo or other diabetes drugs in patients with type 2 diabetes.


Mortality rates in patients with type 2 diabetes taking incretin-based treatments were similar to those for patients taking placebo or other antidiabetic drugs, according to a recent systematic review and meta-analysis.

The review included randomized controlled trials that compared glucagon-like peptide-1 (GLP-1) receptor agonists or dipeptidyl peptidase-2 (DPP-4) inhibitors with placebo or other diabetes drugs in patients with type 2 diabetes. More than 150,000 patients were included the 189 analyzed trials, 112 of which reported patient deaths. Results were published in The BMJ on June 8.

A meta-analysis of all 189 trials found no significant difference in all-cause mortality between the patients taking incretin drugs and the others (odds ratio, 0.96; 95% CI, 0.90 to 1.02; risk difference, 3 fewer events per 1,000 patients over 5 years; 95% CI, 7 fewer to 1 more; moderate-quality evidence). The authors also conducted subgroup analyses, one of which found a possible mortality benefit with GLP-1 agonists. There were reasons to believe that finding to be accurate, including related trends in cardiovascular events and biological plausibility; however, among other limitations, the effect was small and of borderline significance, leading the authors to determine that the association between GLP-1 agonists and decreased mortality had low credibility.

Overall, the authors concluded that current evidence doesn't support the concern that incretin-based drugs increase mortality in patients with type 2 diabetes. “This finding should reassure patients and clinicians and refutes the concern raised by the SAVOR-TIMI trial suggesting increased mortality,” the authors wrote.

The analysis was limited by the relatively short follow-up of the included studies: the longest was 3.8 years and only 40 studies followed patients for more than a year. The review authors called for large randomized trials with adequate follow-up to definitively determine the effects of GLP-1 agonists and DPP-4 inhibitors on all-cause mortality.