E G Dorsey-Treviño1,2, J G González-González1,2,3, N Alvarez-Villalobos2,3,4, V González-Nava2, B M Contreras-Garza2, A Díaz González-Colmenero1,2, G Rodríguez-Tamez2, F J Barrera-Flores1,2, A M Farrell5, V M Montori4,6, R Rodriguez-Gutierrez7,8,9,10. 1. Endocrinology Division, Department of Internal Medicine, University Hospital "Dr. José E. González", Universidad Autonoma de Nuevo Leon, 64460, Monterrey, Mexico. 2. Plataforma INVEST Medicina UANL-KER Unit Mayo Clinic (KER Unit México), Universidad Autonoma de Nuevo Leon, 64460, Monterrey, Mexico. 3. Research Unit, University Hospital "Dr. José E. González", Universidad Autonoma de Nuevo Leon, 64460, Monterrey, Mexico. 4. Knowledge and Evaluation Research Unit in Endocrinology, Mayo Clinic, Rochester, MN, 55905, USA. 5. Mayo Medical Library, Mayo Clinic, Rochester, MN, USA. 6. Division of Endocrinology, Diabetes, Metabolism and Nutrition, Department of Medicine, Mayo Clinic, Rochester, MN, 55905, USA. 7. Endocrinology Division, Department of Internal Medicine, University Hospital "Dr. José E. González", Universidad Autonoma de Nuevo Leon, 64460, Monterrey, Mexico. rodriguezgutierrez.rene@mayo.edu. 8. Plataforma INVEST Medicina UANL-KER Unit Mayo Clinic (KER Unit México), Universidad Autonoma de Nuevo Leon, 64460, Monterrey, Mexico. rodriguezgutierrez.rene@mayo.edu. 9. Knowledge and Evaluation Research Unit in Endocrinology, Mayo Clinic, Rochester, MN, 55905, USA. rodriguezgutierrez.rene@mayo.edu. 10. Division of Endocrinology, Diabetes, Metabolism and Nutrition, Department of Medicine, Mayo Clinic, Rochester, MN, 55905, USA. rodriguezgutierrez.rene@mayo.edu.
Abstract
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.
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.
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