Key result
Dipeptidyl peptidase-4 inhibitors did not significantly increase the risk of major adverse cardiovascular events (OR 1.01) compared to control treatments in patients with type 2 diabetes mellitus.
Why the study?
The study sought to methodically examine cardiovascular sequelae, notably heart failure, among users of DPP-4 inhibitors compared with non-users.
Do DPP-4 inhibitors reduce major adverse cardiovascular events and heart failure in adult patients with type 2 diabetes mellitus?
Meta-Analysis (n=79,010)
Do DPP-4 inhibitors reduce major adverse cardiovascular events and heart failure in adult patients with type 2 diabetes mellitus?
Odds Ratio: 1.01 (95% CI 0.95–1.08)
p-value: p=0.354
DPP-4 inhibitors demonstrate a neutral cardiovascular safety profile, neither increasing nor decreasing the risk of MACE or heart failure in patients with type 2 diabetes.
Affirms neutral cardiovascular safety of DPP-4 inhibitors in type 2 diabetes; confirms prior randomized trial evidence.
Background This examination sought to methodically examine cardiovascular sequelae, notably heart failure, amongst users of dipeptidyl peptidase 4 (DPP-4) inhibitors when compared to non-users. Methods Cochrane, Embase, and PubMed database that compared the use of DPP-4 inhibitors and that reported cardiovascular outcomes and heart failure events in patients with type 2 diabetes mellitus (T2DM) were searched using specific terms. Studies were included if they satisfied the following inclusion criteria: They were randomized trials comparing DPP-4 inhibitors use in patients with T2DM; The studies duration was longer than 24 weeks; And they reported cardiovascular outcomes as their main or second endpoints. Stata 15 MP was used to analyze the data, and odds ratios (OR) with 95% confidence intervals (CI) were used to represent the results. Results A total number of 79,010 participants with T2DM were included. 37,895 patients were assigned to the DPP-4 inhibitor group whereas 41,115 patients were assigned to the control group. Results of this analysis showed that during a mean follow-up period ranging from 24 to 302 weeks, heart failure was not significantly different in the treatment of T2DM patients with versus without DPP-4 inhibitors (OR: 1.06, 95% CI: 0.96,1.18; P = 0.452). Major adverse cardiovascular events (MACE) (include nonfatal myocardial infarction (MI), nonfatal stroke, cardiovascular death) (OR: 1.01, 95% CI: 0.95,1.08; P = 0.354), stroke (OR: 1.01, 95% CI: 0.78,1.30; P = 0.968), MI (OR: 0.89, 95% CI: 0.73,1.07; P = 0.49) and all-cause mortality (OR: 1.03, 95% CI: 0.96,1.11; P = 0.309) were also similarly manifested in both groups. Conclusion The current analysis showed that treatment with DPP-4 inhibitors did not significantly increase cardiovascular outcomes and heart failure in these patients with T2DM indicating that those drugs might be safe to use in terms of cardiovascular events.
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Tuersun et al. (2025) conducted a meta-analysis in Type 2 diabetes mellitus (n=79,010). Dipeptidyl peptidase-4 (DPP-4) inhibitors vs. Placebo or active glucose-lowering medications was evaluated on Major adverse cardiovascular events (MACE) (OR 1.01, 95% CI 0.95-1.08, p=0.354). Dipeptidyl peptidase-4 inhibitors did not significantly increase the risk of major adverse cardiovascular events (OR 1.01) compared to control treatments in patients with type 2 diabetes mellitus.
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