MON-547 Pioglitazone as Add-on Therapy in Patients with Type 2 Diabetes Mellitus Inadequately Controlled with Dapagliflozin and Metformin: A Systematic Review And Meta-analysis of Randomized Controlled Trials

Abstract Disclosure: H. Siddque: None. U. Khan: None. Z. Majeed: None. M. Haris: None. H. Rezq: None. A. Nawaz: None. A. Amin: None. Introduction: Type 2 diabetes mellitus (T2DM) accounts for over 90% of diabetes cases worldwide. Pioglitazone, a thiazolidinedione, enhances insulin sensitivity by activating PPAR-γ. Evidence on its efficacy and safety as an add-on to metformin and SGLT2 inhibitors in inadequately controlled T2DM is limited. This systematic review and meta-analysis evaluates pioglitazone's role as a third-line therapy for improving glycemic control in addition to metformin and Dapagliflozin. Methods: We conducted comprehensive searches across PubMed, CENTRAL, WOS, Scopus, and EMBASE until December 2024. Pooled data were reported using risk ratio (RR) for dichotomous outcomes and mean difference (MD) for continuous outcomes, along with a 95% confidence interval (CI). This systematic review and meta-analysis is registered with PROSPERO ID: CRD42024612005 Results: We included a total of 3 RCTs with a total of 885 patients. Compared to metformin and dapagliflozin combined therapy , Pioglitazone add-on therapy on metformin and dapagliflozin combined therapy was associated with a statistically significant reduction in HbA1c levels (MD: -0.41; 95% CI: -0.54 to -0.27, p = <0.00001, I² = 0%), Pioglitazone add-on therapy increased the likelihood of achieving HbA1c <7% (RR: 2.09; 95% CI: 1.66 to 2.64, p = <0.00001, I² = 0% ) and HbA1c <6.5% (RR: 2.19; 95% CI: 1.36 to 3.53, p = 0.001, I² = 0%). Additionally Pioglitazone add-on therapy was associated with significant reduction in fasting blood sugar (MD: -11.91; 95% CI: -16.34 to -7.48, p = <0.00001, I² = 0%), HOMA-IR (MD: -0.65; 95% CI: -1.05 to -0.25, p = 0.001, I² = 4.89%) and with no change in HOMA-β between the two groups (MD: 2.73; 95% CI: -5.24 to 10.70, p = 0.5, I² = 27.53%). Conclusion: This meta-analysis provides strong evidence supporting the addition of pioglitazone to metformin and Pioglitazone therapy in patients with inadequately controlled T2DM. Future research should focus on longer-term cardiovascular outcomes, optimal dosing strategies, and effectiveness in diverse populations Presentation: Monday, July 14, 2025