Comparison between sodium–glucose cotransporter 2 inhibitors and pioglitazone as additions to insulin therapy in type 2 diabetes patients: A systematic review with an indirect comparison meta‐analysis

AIMS/INTRODUCTION: We aimed to evaluate the efficacy and safety of pioglitazone (PIO) and sodium–glucose cotransporter 2 inhibitors (SGLT2i) as additions to insulin therapy for the management of type 2 diabetes mellitus. MATERIALS AND METHODS: We searched PubMed, EMBASE, the Cochrane Central Register of Controlled Trials and ClinicalTrials.gov through December 2016. Randomized controlled trials published in English that compared SGLT2i plus insulin (SGLT2i/INS) or PIO plus insulin (PIO/INS) with placebo plus insulin (PCB/INS) in type 2 diabetes mellitus patients were included. We compared the efficacy and safety between SGLT2i/INS and PIO/INS indirectly. RESULTS: A total of 14 randomized controlled trials comparing 7,226 participants were included (8 SGLT2i and 6 PIO studies). SGLT2i/INS achieved similar reductions in hemoglobin A1c (weighted mean difference [WMD] −0.01% [−0.1 mmol/mol], 95% confidence interval [CI] −0.25 to 0.22% [−2.7 to −2.4 mmol/mol]; P = 0.896) and fasting plasma glucose (WMD −0.90 mg/dL, 95% CI: −15.50 to 13.71 mg/dL; P = 0.904), and a similar proportion of participants achieved hemoglobin A1c <7.0% (<53.0 mmol/mol; relative risk 0.98, 95% CI: 0.73 to 1.33; P = 0.917) as compared with the PIO/INS group, with greater weight reduction (WMD −4.54 kg, 95% CI: −5.67 to −3.41 kg; P < 0.001). PIO/INS showed non‐significant trends toward a higher risk of hypoglycemia (relative risk 1.15, 95% CI: 0.97 to 1.35; P = 0.102) and higher reduction of total daily insulin doses (WMD −2.45 IU/day, 95% CI: −7.30 to 2.40 IU/day; P = 0.438). CONCLUSIONS: Both PIO and SGLT2i are feasible adjunctive oral agents to pre‐existing insulin therapy in individuals with inadequately controlled type 2 diabetes mellitus.