Comparison and Evaluation of Efficacy and Safety of Sitagliptin and Linagliptin in Adults With Type 2 Diabetes Mellitus: A Bayesian Network Meta-Analysis

Abstract

Aim: A Bayesian network meta-analysis of available randomized controlled trials (RCTs) was conducted to systematically evaluate and compare the efficacy and safety of sitagliptin and linagliptin in treating adults with type 2 diabetes mellitus (T2DM).

Methods: PubMed, Web of Science, Cochrane Library, Embase, ClinicalTrials.gov, Scopus, CNKI, VIP, WanFang, and CBM were searched from inception to October third, 2025. RCTs evaluating the efficacy or safety of sitagliptin or linagliptin in treating adults with T2DM were included, with a follow-up duration of at least 12 weeks and a minimum sample size of 30 participants per treatment group. This study employed a Bayesian random-effects model to calculate relative effect measures with 95% credible intervals (CrIs). Of these, RCTs with outcome assessment at 24 to 54 weeks were incorporated into the primary analysis, and the rest into the sensitivity analysis. The risk of bias was assessed using the Cochrane Risk of Bias Tool (2.0). The certainty of evidence was evaluated using the Confidence in Network Meta-Analysis framework. This study was pre-registered on the International Prospective Registry of Systematic Reviews (No. CRD42024500280).

Results: A total of 87 RCTs involving 64,517 participants were included. Among them, 61 RCTs with 28,715 participants were included in the primary analysis. Compared with placebo, both sitagliptin 100 mg/day and linagliptin 5 mg/day demonstrated significantly superior efficacy in reducing hemoglobin A_1c. The mean difference (MD) was -0.64% [95% CrI, -0.75, -0.53] (high confidence) for sitagliptin 100 mg/day and -0.59% [-0.69, -0.48] (moderate confidence) for linagliptin 5 mg/day. Similarly, both sitagliptin 100 mg/day (MD, -15.16 mg/dL [95% CrI, -18.82, -11.55]; high confidence) and linagliptin 5 mg/day (-13.88 mg/dL [-17.54, -10.04]; moderate confidence) were significantly superior to placebo in reducing fasting plasma glucose. No significant differences were observed in all included efficacy outcomes between sitagliptin 100 mg/day and linagliptin 5 mg/day. Compared with placebo, neither sitagliptin 100 mg/day nor linagliptin 5 mg/day was associated with a significant increase in the risk of adverse events. The relative risk was 1.06 [95% CrI, 0.99, 1.14] (moderate confidence) for sitagliptin 100 mg/day and 1.00 [0.96, 1.05] (low confidence) for linagliptin 5 mg/day. No significant increase in risk was observed for any of the included safety outcomes with either sitagliptin 100 mg/day or linagliptin 5 mg/day compared with placebo. Except for all-cause mortality and cardiovascular mortality, where sitagliptin 100 mg/day showed an uncertain advantage over linagliptin 5 mg/day, no significant differences were observed between them in all other included safety outcomes.

Conclusion: Sitagliptin 100 mg/day and linagliptin 5 mg/day demonstrated favorable and equivalent antidiabetic efficacy and safety profiles. However, neither was significantly superior to the other included antidiabetic drugs on glycemic control.

Keywords: Bayesian network meta‐analysis; efficacy; linagliptin; safety; sitagliptin; type 2 diabetes mellitus.