Sodium-glucose cotransporter 2 inhibitor plus pioglitazone vs pioglitazone alone in patients with diabetes mellitus: A systematic review and meta-analysis of randomized controlled trials

Aims: To evaluate the efficacy and safety of combined therapy with sodium-glucose cotransporter 2 (SGLT-2) inhibitors plus pioglitazone versus pioglitazone alone in type 2 diabetic patients. Materials and Methods: Systematic literature searches were performed across PubMed, EMBASE, Cochrane Central Register of Controlled Trials, and clinicaltrials. gov from 1966 to September 2018 to identify randomized, controlled trials. Mean difference (MD) or odds ratio (OR) was used to evaluate efficacy and safety-endpoints (active group vs control group), wherever appropriate. Heterogeneity was assessed by P value of chi(2) statistics and I-2. Results: Four randomized controlled trials with 1411 diabetic patients were included. Pooling data from included trials showed that HbA1c change was significantly larger in both low-dose SGLT-2 inhibitors (MD: -0.59%, 95% CI: - 0.77 to - 0.41%) and high-dose SGLT-2 inhibitors (MD: - 0.65%, 95% CI: -0.78 to -0.53%) plus pioglitazone than pioglitazone alone in 24-26 weeks. Favourable outcomes were also found in fasting blood glucose level reduction and more patients achieving HbA1c <7% in SGLT-2 inhibitor plus pioglitazone (OR: 3.21, 95% CI: 1.99 to 5.16). Also, SGLT-2 inhibitor plus pioglitazone vs pioglitazone, reduced weight and blood pressure. The risks of death, heart failure, hypoglycaemia and urinary tract infection were not different between active and control groups although genital tract infection was more frequently seen in SGLT-2 inhibitor group. Conclusions: Compared to pioglitazone alone, SGLT-2 inhibitor plus pioglitazone improved glycaemic control, reduced body weight and lowered blood pressure, but increased genital tract infection.