Efficacy and Safety of Pioglitazone Add‐On in Patients With Type 2 Diabetes Mellitus Inadequately Controlled With Metformin and Dapagliflozin: A Systematic Review and Meta‐Analysis of Randomised Controlled Trials
Abstract
ABSTRACT Background 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 glycaemic control in addition to metformin and Dapagliflozin. Methodology 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 three RCTs with 885 patients. Pioglitazone add‐on therapy significantly reduced HbA1c levels (MD: −0.41; 95% CI: −0.54 to −0.27, p = < 0.00001, I2 = 0%), fasting blood glucose (MD: −11.91; 95% CI: −16.34 to −7.48, p = < 0.00001, I2 = 0%), Homeostatic Model Assessment for Insulin Resistance (HOMA‐IR) (MD: −0.65; 95% CI: −1.05 to −0.25, p = 0.001, I2 = 4.89%), increased the rate 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%). However, there was no difference regarding Homeostasis model assessment of β‐cell…
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Evidence Hub reads this as a meta-analysis, done in people. Its evidence level is 1 of 5 (Highest · pooled evidence). Pooled evidence from several studies sits at the top of the evidence pyramid. Reported size: 885 participants or records.
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