Effects of semaglutide on mortality, cardiovascular, and kidney outcomes across the cardio-kidney-metabolic continuum: a systematic review and meta-analysis

Published May 26, 2026Cardiovascular diabetology

Semaglutide's impact on death rates, heart, and kidney health across related metabolic conditions

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Page updated Jun 27, 2026

Abstract

Essence

Across randomized trials, semaglutide reduced several mortality, cardiovascular, and kidney outcomes but not nonfatal stroke.

Evidence

This systematic review and meta-analysis pooled eight placebo-controlled randomized trials with 39,204 patients and found lower all-cause mortality, cardiovascular mortality, MACE, nonfatal myocardial infarction, worsening heart failure, and kidney outcomes with semaglutide.

Caveat

The synthesis spans diverse cardio-kidney-metabolic populations and found no significant effect on nonfatal stroke, with major adverse limb events treated only as exploratory.

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BACKGROUND: Semaglutide, a glucagon-like peptide-1 (GLP-1) receptor agonist, has demonstrated cardiometabolic benefits in randomized controlled trials (RCTs). However, its overall effects on mortality, cardiovascular (CV) and kidney outcomes have not been comprehensively synthesized. This meta-analysis aimed to assess the prognostic impact of semaglutide across the cardio-kidney-metabolic continuum.

METHODS: A systematic literature search was conducted to identify all eligible RCTs comparing the prognostic effects of semaglutide with placebo across diverse patient populations. Primary outcomes were all-cause and CV mortality. Secondary outcomes included major CV and kidney events, while major adverse limb events (MALE) were analyzed as an exploratory endpoint. A random-effects model was used to pool hazard ratios (HRs) and 95% confidence intervals (CIs).

RESULTS: Eight trials encompassing 39,204 patients were included. In patients treated with semaglutide a significant reduction of all-cause (HR, 0.84; 95% CI, 0.77-0.92; p = 0.0001) and CV mortality (HR, 0.83; 95% CI, 0.72-0.95; p = 0.0078), major adverse CV events (MACE, HR, 0.82; 95% CI, 0.77-0.87; p < 0.0001), nonfatal myocardial infarction (MI, HR, 0.75; 95% CI, 0.68-0.84; p < 0.0001), worsening heart failure (HF, HR, 0.84; 95% CI, 0.73-0.98; p = 0.0245), and kidney outcomes (HR, 0.83; 95% CI, 0.73-0.95; p = 0.0080) was observed compared to placebo. No significant effects were observed for nonfatal stroke.

CONCLUSIONS: Treatment with semaglutide, compared to placebo, is associated with significant lower incidence of all-cause and CV mortality, as well major CV and kidney events across the continuum of cardio-kidney-metabolic syndrome.