Efficacy and safety comparison between pioglitazone and linagliptin in combination with metformin among patients with Type 2 diabetes mellitus: A meta-analysis of randomized controlled trials

Objective: To compare the safety and efficacy of linagliptin with pioglitazone in combination therapy of metformin for the management of type 2 diabetes mellitus (T2DM). Materials and Methods: A meta-analayis research design is applied to evaluate the primary and secondary outcomes. Literature search was carried out using databases such as PubMed, Cochrane Library, MEDLINE Complete, Scopus, Clinical Trial Registry, and Web of Science. Studies were considered eligible if the eligibility criteria were met. Cochrane Collaboration Tool was used to assess the risk of bias in randomized clinical trials. Results: A total of 170 citations were identified during the database search. Further evaluation of articles confirmed 16 clinical trials suitable for the research which were randomized, double-blinded, and published as full articles. The articles were evaluated with low risk of bias and high-quality evidence. The mean baseline hemoglobin A1c (HbA1c) ranged from 6.93% to 9.99% and 7.1% to 8.89% for linagliptin with metformin and pioglitazone with metformin groups, respectively. Two among the 12 groups show a slight increase in the mean HbA1c levels which is nonsignificant due to their sample size. Overall, the combination therapy of linagliptin with metformin led to a reduction of 1.35% which is significantly higher than pioglitazone combined with metformin which led to a 1.27% reduction. The mean baseline values of fasting plasma glucose levels varied from 158.2 mg/dl to 198.0 mg/dl in linagliptin plus metformin group, whereas in pioglitazone plus metformin group, the values varied from 137.0 mg/dL to 212.4 mg/dL. The high heterogeneity could refer to the inconsistencies between the studies. The combination of linagliptin with metformin showed a significant reduction of 0.56% in body mass index, whereas pioglitazone with metformin led to a 0.37% reduction. Conclusion: The findings showed better efficacy profiling of lingaliptin–metformin combination compared with pioglitazone combination therapy.