Journal of the Endocrine SocietyApr 29, 2020

Comparing Two Diabetes Treatments: GLP-1 Receptor Agonists and SGLT2 Inhibitors for Type 2 Diabetes

GLP-1 Therapies Weekly Brief ↗PubMed ↗DOI ↗OA ↗

Updated Apr 1, 2026

Abstract

A meta-analysis of 85,219 subjects indicates that glucagon-like peptide-1 receptor agonists (GLP-1 RA) and sodium-glucose cotransporter 2 inhibitors (SGLT2i) similarly reduce (MACE) and cardiovascular deaths (CVD).

Both GLP-1 RA and SGLT2i are associated with reductions in MACE and CVD compared to controls, with no significant preference for either class.
SGLT2i significantly reduce (HHF), while GLP-1 RA do not show a similar benefit.
Both drug classes demonstrate reductions in renal outcomes, but neither shows a preferential difference in effectiveness.
Serious adverse events related to SGLT2i include mycotic genital infections and diabetic ketoacidosis, while gastrointestinal intolerance is noted for GLP-1 RA.
Meta-regression suggests that the benefits of SGLT2i on CVD and HHF may be greater in populations with higher underlying rates of MACE.

Simplified

CONTEXT: Cardiovascular outcome trials (CVOT) of glucagon-like peptide-1 receptor agonists (GLP-1 RA) and sodium-glucose cotransporter 2 inhibitors (SGLT2i) demonstrated reduction of (MACE), cardiovascular deaths (CVD), and renal outcomes.

OBJECTIVE: Assist in the prescribing decision regarding severity of illness and risk for adverse events.

DESIGN: Meta-analysis of the major CVOT and previous meta-analyses.

MAIN OUTCOME MEASURES: Six trials of GLP-1 RA (51 762 subjects) and 4 trials of SGLT2i (33 457 subjects) showed both drug classes reduced MACE and CVD versus controls, with neither class preferred (comparison GLP1-RA vs SGLT2i: relative rate [rr] MACE 1.09, 95% confidence interval [CI] 0.97, 1.22, = ns; rr CVD 1.04, 95% CI 0.87, 1.24, = ns). (HHF) improved with SGLT2i (rr 0.68, CI 0.61, 0.76, < 0.001) but not with GLP-1 RA, (rr 0.93, CI 0.86,1.03, = ns). Meta-regression suggested benefits of the SGLT2i on CVD and HHF were accentuated with the underlying rate of MACE in the cohort (i.e., >10 events/1000pt*year). GLP-1 RA and SGLT2i showed reduction in renal outcomes (GLP-1 RA rr 0.83, CI 0.75, 0.91, p ≤ 0.001, SGLT2i rr 0.67, CI 0.57, 0.79, < 0.001) without a preferential difference (GLP-1 RA vs SGLT2i, rr 1.24, CI 0.95, 1.61, = ns; relative difference (rd) 0.005, CI -0.011, 0.021, = ns). Serious adverse events for SGLT2i were mycotic genital infections in women (number needed to harm [NNH] = 13 and diabetic ketoacidosis NNH = 595. Gastrointestinal intolerance was the serious adverse event in the GLP1-RA class (NNH = 35). P P P P P P P

CONCLUSION: GLP-1 RA and SGLT2i classes showed similar reduction in MACE, CVD, and renal outcomes. SGLT2i have advantages over GLP-1 RA in reduction in HHF.

Key numbers

51 762

Subjects in GLP-1 RA Trials

Total number of subjects across six major GLP-1 RA trials.

33 457

Subjects in SGLT2i Trials

Total number of subjects across four major SGLT2i trials.

0.68

Decrease in

Relative rate for with SGLT2i.

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Comparing Two Diabetes Treatments: GLP-1 Receptor Agonists and SGLT2 Inhibitors for Type 2 Diabetes

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