Sodium-glucose cotransporter 2 (SGLT-2) inhibitors and glucagon-like peptide 1 (GLP-1) agonists reduce mortality rates better than dipeptidyl peptidase 4 (DPP-4) inhibitors, placebo, or no treatment in patients with type 2 diabetes, according to a study published in JAMA.

Sean L Zheng, BM, BCh, MA, MRCP, of the Department of Endocrinology at the Imperial College Healthcare NHS Foundation Trust in London, and associates compared the effectiveness of SGLT-2 inhibitors, GLP-1 agonists, and DPP-4 inhibitors on all-cause mortality (primary outcome), cardiovascular mortality, heart failure, myocardial infarction, unstable angina, and stroke (secondary outcomes) in patients with type 2 diabetes.

In the network meta-analysis of 236 randomized trials, 176,310 participants were administered either SGLT-2 inhibitors, GLP-1 agonists, DPP-4 inhibitors, placebo, or no treatment and assessed with a follow-up of a minimum of 12 weeks.

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Absolute risk differences (RD) and hazard ratios (HR) reported for SGLT-2 inhibitors (RD, -1.0%; HR, 0.80) and GLP-1 agonists (RD, -0.6%; HR, 0.88) resulted in significantly reduced all-cause mortality compared with the control cohorts. DPP-4 inhibitors were not associated with a mortality reduction compared with control groups (RD, 0.1%; HR, 1.02).

Compared with DPP-4 inhibitors, both SGLT-2 inhibitors (RD, -0.9%; HR, 0.78) and GLP-1 agonists (RD, -0.5%; HR, 0.86) were more strongly correlated with reduced mortality. Both SGLT-2 inhibitors and GLP-1 agonists resulted in significantly reduced cardiovascular mortality, heart failure, and myocardial infarctions, compared with the control groups.

In addition, GLP-1 agonists were linked to elevated risks for adverse events, resulting in trial withdrawal compared with SGLT-2 inhibitors (RD, 5.8%; HR, 1.80) and DPP-4 inhibitors (RD, 3.1%; HR, 1.93).

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“In this network meta-analysis, the use of SGLT-2 inhibitors or GLP-1 agonists was associated with lower mortality than DPP-4 inhibitors or placebo or no treatment,” the authors wrote. “Use of DPP-4 inhibitors was not associated with lower mortality than placebo or no treatment.

“Of the 3 classes tested, SGLT-2 inhibition may be preferred over the incretin-based therapies based on their association with lower mortality and their favorable adverse event profile,” concluded the investigators.


Zheng SL, Roddick AJ, Aghar-Jaffar R, et al. Association between use of sodium-glucose cotransporter 2 inhibitors, glucagon-like peptide 1 agonists, and dipeptidyl peptidase 4 inhibitors with all-cause mortality in patients with type 2 diabetes: a systematic review and meta-analysis. JAMA. 2018;319(15):1580–1591.