Semaglutide reduces cardiovascular events in type 2 diabetes: a systematic review and meta-analysis highlighting enhanced benefits in chronic kidney disease

Nov 4, 2025European journal of medical research

Semaglutide lowers heart problems in type 2 diabetes, with stronger benefits for people with chronic kidney disease

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Abstract

Semaglutide reduced the risk of cardiovascular death by 23% in patients with type 2 diabetes.

In 17 studies involving 40,632 patients, semaglutide significantly lowered the risk of by 18%.
Significant reductions in nonfatal myocardial infarction and nonfatal stroke were observed, with reductions of 18% and 32%, respectively.
The cardiovascular event reductions were more pronounced in type 2 diabetes patients with , showing a risk reduction of 24-37%.
Semaglutide also improved modifiable cardiovascular risk factors, including a decrease in systolic blood pressure by 8.02 mmHg and low-density lipoprotein by 12.62 mg/dL.
No significant effects on estimated glomerular filtration rate or urinary albumin-to-creatinine ratio were noted.

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BACKGROUND: Cardiovascular disease (CVD) disproportionately affects type 2 diabetes (T2D) patients with (CKD). Although semaglutide shows cardiometabolic benefits, its efficacy across CVD endpoints and high-risk CKD subgroups remains underexplored.

METHODS: We systematically reviewed PubMed, Embase, Cochrane, Web of Science (through September 2025) for randomized trials and observational studies evaluating oral semaglutide versus placebo in T2D. Data synthesis employed hazard ratios (HRs) and mean differences (MDs) with 95% confidence intervals (CIs).

RESULTS: Across 17 studies (n = 40, 632 patients), semaglutide significantly reduced the risk of cardiovascular (CV) death by 23% [HR 0.77, 95% CI (0.68, 0.88)], (MACE) by 18% [HR 0.82, 95% CI (0.75, 0.90)], expanded MACE by 22% [HR 0.78, 95% CI (0.70, 0.85)], nonfatal myocardial infarction (MI) by 18% [HR 0.82, 95% CI (0.68, 0.92)], and nonfatal stroke by 32% [HR 0.68, 95% CI (0.56, 0.83)]. The reductions in CV events were most pronounced in T2D patients with CKD (24-37% risk reduction vs. 13-35% in T2D alone or with CVD). Semaglutide also significantly improved modifiable CV risk factors, reducing systolic/diastolic blood pressure (SBP/DBP) decreased by 8.02/3.71 mmHg, and low-density Lipoprotein (LDL) decreased by 12.62 mg/dL, while increasing high-density lipoprotein (HDL) by 1.44 mg/dL. However, semaglutide had no significant effect on estimated glomerular filtration rate (eGFR) and urinary albumin-to-creatinine ratio (UACR).

CONCLUSION: Semaglutide confers robust cardiovascular protection in T2D, with amplified benefits in patients with comorbid CKD. It confers a collective advantage by simultaneously addressing multiple risk factors including blood pressure and lipoprotein, positioning it as a comprehensive treatment strategy for high-risk populations. This analysis is the first to synthesize evidence across CKD subgroups, supporting prioritizing semaglutide in T2D patients with CKD. Further research should clarify mechanisms underlying CKD-specific benefits and refine risk-stratified treatment algorithms.

Key numbers

23%

Reduction in Cardiovascular Death

Reduction in cardiovascular death rate among patients treated with .

18%

Reduction in ()

Decrease in incidence in patients receiving .

8.02 mmHg

Systolic Blood Pressure Reduction

Average decrease in systolic blood pressure with treatment.

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Semaglutide reduces cardiovascular events in type 2 diabetes: a systematic review and meta-analysis highlighting enhanced benefits in chronic kidney disease

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