Effect of sodium–glucose cotransporter 2 inhibitors on insulin resistance; a systematic review and meta-analysis

Recent studies have indicated that Sodium–GLucose co-Transporter 2 Inhibitors (SGLT2Is) may increase insulin sensitivity (IS); however, these results are heterogeneous and need to be systematically assessed. We searched MEDLINE/PubMed, Embase, Web of Science, Scopus, Cochrane Library, Ovid, and ProQuest using a predefined search query. Randomized clinical trials on SGLT2Is with a passive control group or metformin controlled group were included. Risk of bias assessment was performed using the Cochrane risk of bias assessment tool. Meta-analysis was performed separately on studies with type 2 diabetes mellitus (T2DM) population and studies with non-T2DM population and also for passive- and active-controlled studies using standardized mean difference (SMD) as the measure of the effect size. Subgroup analysis was performed according to different types of SGLT2Is. Meta-regression analysis was performed according to the dose and duration of intervention. Twenty-two studies (6 on non-T2DM population) with a total of 1421 (243 non-T2DM) patients were included. Six studies (3 on T2DM and 3 on non-T2DM) were controlled by metformin, and others were passively controlled. SGLT2Is could significantly increase IS in T2DM patients (SMD = 0.72 [0.32–1.12]). SGLT2Is could reduce insulin resistance in non-T2DM population, but this was not significant. SGLT2Is were not inferior to metformin in reducing insulin resistance. Subgroup analysis indicated that dapagliflozin could significantly increase IS, but empagliflozin was not associated with significant improvement in IS. Meta-regression analysis indicated no effect for dose but duration of SGLT2I administration on IS. SGLT2Is, particularly dapagliflozin, could increase IS. These results need to be consolidated by further studies.