Sodium-glucose cotransporter 2 (SGLT-2) inhibitors and microvascular outcomes in patients with type 2 diabetes: systematic review and meta-analysis

Purpose: The effect of the sodium-glucose 2 (SGLT-2) inhibitors on microvascular complications remains uncertain. We performed a systematic review to determine the efficacy of the SGLT-2 inhibitors on microvascular outcomes in patients with type 2 diabetes. Methods: A comprehensive search was performed using Ovid, MEDLINE, EMBASE, Web of Science, and Scopus from inception to May 2019. Randomized trials comparing SGLT-2 inhibitors with placebo or other medication for type 2 diabetes for ≥ 4 weeks were included. Diabetes-related microvascular complications such as nephropathy, retinopathy, neuropathy, and peripheral vascular disease were evaluated. A random-effect model using mean differences for continuous outcomes and risk ratio for dichotomous outcomes was used to synthesize data. PROSPERO (CRD 42017076460). Results: A total of 40 RCTs with overall moderate quality of evidence were included. SGLT-2 inhibitors reduced the risk of renal-replacement therapy (0.65; 95% CI 0.54–0.79), renal death (0.57; 95% CI 0.49–0.65), and progression of albuminuria (0.69; 95% CI 0.66–0.73). Conversely, they appeared ineffective in maintaining eGFR (0.33; 95% CI − 0.74 to 1.41) or reducing serum creatinine (− 0.07; 95% CI − 0.26 to 0.11), whereas urine albumin–creatinine ratio (− 23.4; 95% CI − 44.6 to − 2.2) was reduced. Risk of amputation was non-significant (1.30; 95% CI 0.93–1.83). No available data were found regarding neuropathy and retinopathy to perform a quantitative analysis. Conclusion: SGLT-2 inhibitors may reduce the risk of renal patient-important outcomes but fail to improve surrogate outcomes. Apparently, no increased risk of amputations was observed with these medications. No data were available regarding other microvascular complications.