Efficacy and safety of insulin sensitisers for treating type 2 diabetes: a network meta-analysis.

Purpose: Thiazolidinediones (TZDs), including pioglitazone and rosiglitazone, and non-TZD insulin sensitisers (chiglitazar sodium) demonstrate potential; however, their comparative efficacy and safety remain unclear. We aimed to analyse the efficacy and safety of commonly used insulin sensitisers, including chiglitazar sodium, sitagliptin, pioglitazone, and rosiglitazone for treating type 2 diabetes mellitus (T2DM).

Methods: A computer-based search was conducted in the China National Knowledge Infrastructure, Wanfang Data, the VIP database, PubMed, Embase, and Cochrane Library databases from the establishment date of each database to January 2025. Included study quality was evaluated using the Cochrane risk of bias tool. Surface under the cumulative ranking curve was calculated for each outcome indicator to compare the efficacy and safety of different interventions.

Results: In reducing haemoglobin A1c, 8 mg of rosiglitazone was superior over 100 mg sitagliptin, 30 mg pioglitazone, and 15 mg pioglitazone (P < 0.05), with no significant differences among the remaining medications. To reduce fasting plasma glucose, 45 mg of pioglitazone was more effective than any dosage of chiglitazar sodium, sitagliptin, or rosiglitazone (P < 0.05). Regarding safety, the incidence rate of adverse reactions was higher with 45 mg of pioglitazone than with 8 mg of rosiglitazone (P < 0.05), with no significant differences in adverse events among other medications.

Conclusion: Compared with placebo, all four drugs were safe and effective in the treatment of T2DM. High-dose TZDs may be more effective than mitiglinide and sitagliptin. However, 45 mg of pioglitazone was associated with a higher incidence of adverse events, warranting close monitoring of its safety profile.