A comparison of HbA1c reduction among DPP-4 inhibitors in patients with type 2 diabetes mellitus: A network meta-analysis of randomized controlled trials

Abstract

This study aimed to provide a head-to-head comparison of DPP-4 inhibitors in reducing HbA1c levels among patients with type 2 diabetes mellitus (T2DM). We carried out a network meta-analysis study between January and March 2026. Article searching was conducted in Web of Science, EMBASE, PUBMED, and Cochrane. The required data from each article were extracted using a pilot form and analyzed using a Z test to assess the association and effect size. A total of 43 articles were employed in our study. Our findings confirmed that T2DM patients treated with DPP-4 inhibitors, either as single or combination treatment, had lower HbA1C reduction compared to placebo. The highest HbA1C reduction was observed in T2DM treated with alogliptin, linagliptin, and vildagliptin; and the lowest HbA1C reduction was found in sitagliptin and saxagliptin. The indirect comparison suggested that alogliptin, linagliptin, and vildagliptin ranked higher in HbA1c reduction than saxagliptin and sitagliptin, with alogliptin showing the highest probability of being the most effective treatment according to the P-score ranking. In conclusion, alogliptin, linagliptin, and vildagliptin may be considered the first choice of DPP-4 inhibitors for treating T2DM patients. However, the safety and tolerability of these products should also be considered.