Cardiovascular and renal outcomes of GLP-1 receptor agonists vs. DPP-4 inhibitors and basal insulin in type 2 diabetes mellitus: A systematic review and meta-analysis

Objective: To compare the cardiovascular and renal outcomes of GLP-1 RA versus DPP4i and basal insulin in the management of T2DM. Methods: Data from 22 studies involving over 200,000 participants were pooled using the inverse variance method and random-effects meta-analysis. The review was reported in accordance with PRISMA. Results: Compared with DPP4i, treatment with GLP-1 RA was associated with a greater benefit on composite cardiovascular outcomes (HR:0.77, 95% CI:0.69–0.87), myocardial infarction (HR:0.82, 95% CI:0.69–0.97), stroke (HR:0.83, 95% CI: 0.74–0.93), cardiovascular mortality (HR:0.76, 95% CI:0.68–0.85) and all-cause mortality (HR:0.65, 95% CI:0.48–0.90). There was no difference in effect on heart failure (HR:0.97, 95% CI:0.82–1.15). Compared with basal insulin, GLP-1 RA was associated with better effects on composite cardiovascular outcomes (HR:0.62, 95% CI:0.48–0.79), heart failure (HR:0.57, 95% CI:0.35–0.92), myocardial infarction (HR:0.70, 95% CI:0.58–0.85), stroke (HR:0.50, 95% CI:0.40–0.63) and all-cause mortality (HR:0.31, 95% CI:0.20–0.48). Evidence from a small number of studies suggests that GLP-1 RA had better effects on composite and individual renal outcomes, such as eGFR, compared with either DPP4i and basal insulin. Conclusion: Available evidence suggests that treating T2DM with GLP-1 RA can yield better benefits on composite and specific cardiorenal outcomes than with DPP4i and basal insulin. PROSPERO Registration Number: CRD42022335504.