GLP-1 Agonists, SGLT-2 Inhibitors Associated With Lower Mortality in T2D

cardiovascular system
cardiovascular system
Investigators compared effectiveness of SGLT-2 inhibitors, GLP-1 agonists, and DPP-4 inhibitors on cardiovascular outcomes and mortality.

Researchers have found both glucagon-like peptide 1 (GLP-1) agonists and sodium-glucose cotransporter 2 (SGLT-2) inhibitors are associated with reduced mortality in individuals with type 2 diabetes, according to a study recently published in the Journal of the American Medical Association.          

This systematic review and meta-analysis of 236 randomized clinical trials included 176,310 subjects with type 2 diabetes and a minimum 12-week follow-up. Researchers compared the efficacies of GLP-1 agonists, SGLT-2 inhibitors, and dipeptidyl peptidase 4 (DPP-4) inhibitors with placebo groups or with each other. The primary outcome was all-cause mortality, with heart failure events, myocardial infarction, stroke, cardiovascular mortality, and unstable angina as secondary outcomes.

Compared with control groups, the 2 treatments linked with a significant reduction in all-cause mortality were GLP-1 agonists (absolute risk difference [RD] –0.6%; hazard ratio [HR] 0.88) and SGLT-2 inhibitors (absolute RD –1.0%; HR, 0.80). Compared with DPP-4 inhibitors, GLP-1 agonists (absolute RD –0.5%; HR 0.86) and SGLT-2 inhibitors (absolute RD –0.9%; HR 0.78) were linked with reduced mortality. DPP-4 inhibitors did not correlate with a significant reduction in all-cause mortality (absolute RD 0.1%; HR 1.02) compared with control groups.

In regard to cardiovascular mortality, both GLP-1 (absolute RD –0.5%; HR 0.85) and SGLT-2 inhibitors (absolute RD –0.8%; HR 0.79) correlated with significant reduction compared with control groups. SGLT-2 inhibitors correlated with reduced rates of myocardial infarction (absolute RD –0.6%; HR 0.86) and heart failure events (absolute RD, –1.1%; HR, 0.62) in comparison with control groups. However, GLP-1 agonists were linked with more adverse events that resulted in discontinuation of the trial than were DPP-4 inhibitors (absolute RD 3.1%; HR 1.93) or SGLT-2 inhibitors (absolute RD 5.8%; HR 1.80).

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Researchers conclude that “the use of SGLT-2 inhibitors or GLP-1 agonists was associated with lower mortality than DPP-4 inhibitors or placebo or no treatment. Use of DPP-4 inhibitors was not associated with lower mortality than placebo or no treatment.”


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-analysisJAMA. 2018;319(15):1580-1591.