Key result
SGLT2i plus GLP-1RA cuts MI risk ~21% and reduces stroke vs monotherapy in T2D.
Why the study?
Although SGLT2 inhibitors and GLP-1 receptor agonists offer cardioprotection in T2DM, the comparative effect of their monotherapy versus combined use on myocardial infarction and stroke needed evaluation.
Does combination therapy with SGLT2 inhibitors and GLP-1 receptor agonists reduce myocardial infarction and stroke in adults with type 2 diabetes mellitus compared to monotherapy with either agent?
Meta-Analysis
Does combination therapy with SGLT2 inhibitors and GLP-1 receptor agonists reduce myocardial infarction and stroke in adults with type 2 diabetes mellitus compared to monotherapy with either agent?
Hazard Ratio: 0.79 (95% CI 0.7–0.88)
p-value: p=<0.001
In adults with type 2 diabetes, combining SGLT2 inhibitors and GLP-1 receptor agonists may provide additive reductions in stroke risk compared to monotherapy, while the observed reduction in myocardial infarction appears primarily driven by the GLP-1RA component.
May support combination therapy for additive CV risk reduction in T2D; extends individual SGLT2i/GLP-1RA benefits.
Sodium-glucose cotransporter-2 inhibitors (SGLT2is) and glucagon-like peptide-1 receptor agonists (GLP-1RAs) offer cardioprotection in type 2 diabetes mellitus (T2DM). We evaluated their monotherapy versus their combined use for prevention of myocardial infarction (MI) and stroke. Conducted according to preferred reporting items for systematic reviews and meta-analyses (PRISMA) 2020 guidelines, five databases were systematically searched through November 2025 for studies evaluating use of SGLT2i and GLP-1RA in combination versus their monotherapy in adults with T2DM. Hazard ratios (HRs) for MI and stroke were pooled utilizing random-effects models. Subgroup interaction testing and grading of recommendations assessment, development, and evaluation (GRADE) certainty assessments were performed. Of the studies, eight comprising ten comparisons were included. Combination therapy was associated with a lower overall risk of MI (HR 0.79, 95% CI 0.70–0.88; I2 = 72.8%) and stroke (HR 0.85, 95% CI 0.77–0.93; I2 = 63.5%) compared with their monotherapy. For MI, combination therapy significantly outperformed SGLT2i monotherapy (HR 0.74, 95% CI 0.60–0.90) but not GLP-1RA monotherapy (HR 0.80, 95% CI 0.55–1.16). For stroke reduction, combination therapy outperformed both SGLT2i (HR 0.73, 95% CI 0.54–0.99) and GLP-1RA (HR 0.92, 95% CI 0.88–0.96) monotherapy. Cerebrovascular benefit appeared stronger in adults > 65 years (HR 0.50, 95% CI 0.37–0.68). Overall certainty of evidence was very low. In adults with T2DM, SGLT2i and GLP-1RA combination therapy may be associated with lower risks of MI and stroke compared with their monotherapy. While the MI benefit appears primarily to be driven by GLP-1RA, combination therapy yields an additive reduction in stroke risk, particularly in older adults. Given the very low certainty of evidence, these hypothesis-generating findings require confirmation through dedicated prospective trials. https://www.crd.york.ac.uk/PROSPERO/view/CRD420261320374 .
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Ghafoury et al. (2026) conducted a meta-analysis in Type 2 diabetes mellitus. Combination therapy with SGLT2 inhibitors and GLP-1 receptor agonists vs. SGLT2 inhibitor or GLP-1 receptor agonist monotherapy was evaluated on Myocardial infarction (HR 0.79, 95% CI 0.70-0.88, p=<0.001). Combination therapy with SGLT2 inhibitors and GLP-1 receptor agonists reduced the risk of myocardial infarction (HR 0.79) and stroke (HR 0.85) compared to monotherapy in adults with type 2 diabetes.
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