OBJECTIVES

To compare the effect of SGLT2Is on glycemic control by conducting a network meta-analysis (NMA) in adults with uncontrolled T2DM on diet/exercise or metformin, including a subgroup analysis in Asian population.

METHODS

MEDLINE, Cochrane, and Google Scholar were searched for randomized controlled trials. Studies published between January-2005 to December-2019, with a minimum follow-up of 24 weeks, and reporting change in HbA1c (%) from baseline were included. The NMA was conducted in a frequentist framework using R package netmeta (3.5.1). Both fixed-effect and random-effects models were used; results of random-effects model are reported. A subgroup analysis with Asian population was also conducted. Separate NMAs were conducted for SGLT2Is monotherapy and their combinations with metformin.

RESULTS

Of 511 retrieved studies, 15 were included in the monotherapy and 9 in the combination analysis. Ipragliflozin50mg showed highest efficacy (mean HbA1c difference [95% CI]) compared with other SGLT2Is: -0.273 (-0.731;0.185) vs Cana100mg, -0.227 (-0.707;0.254) vs Cana200mg, -0.25 (-0.769;0.269) vs Cana300mg, -0.456 (-0.909;-0.004) vs Dapa10mg, -0.809 (-1.347;-0.271) vs Dapa2.5mg, -0.565 (-1.018;-0.111) vs Dapa5mg, -0.555 (-0.975;-0.135) vs Empa10mg, -0.457 (-0.876;-0.037) vs Empa25mg, -1.108 (-1.537;-0.68) vs Ertu15mg, -0.893 (-1.325;-0.462) vs Ertu5mg, -0.49 (-1.03;0.05) vs Luse2.5mg, -0.481 (-1.021;0.059) vs Tofo10mg, -0.261 (-0.8;0.278) vs Tofo20mg, -0.408 (-0.947;0.131) vs Tofo40mg. In the subgroup analysis also, Ipragliflozin had the highest efficacy (mean HbA1c difference [95% CI]): -0.22 (-0.441;0.001) vs Cana100mg, -0.2 (-0.421;0.021) vs Cana200mg, -0.43 (-0.719;-0.141) vs Dapa10mg, -0.5 (-0.794;-0.206) vs Dapa5mg, -0.481 (-0.801;-0.161) vs Tofo10mg, -0.261 (-0.58;0.058) vs Tofo20mg, -0.408 (-0.727;-0.089) vs Tofo40mg. Similar results were obtained for SGLT2Is combination analysis. In all analyses, Ipragliflozin50mg had the highest probability of being ranked at the first place.

CONCLUSIONS

Ipragliflozin50mg was the most effective versus other SGLT2Is for HbA1c reduction, both as a monotherapy or in combination with metformin in patients with uncontrolled T2DM on diet/exercise or metformin and the Asian subgroup of this population.