Effect of metformin on microvascular outcomes in patients with type 2 diabetes: A systematic review and meta-analysis.

AIMS: Examine the efficacy of metformin compared to placebo or other glucose-lowering medications on microvascular outcomes in patients with Type 2 Diabetes Mellitus (T2DM). METHODS: MEDLINE, EMBASE, Web of Science, and Scopus were searched from database inception to March 2020. We included randomized clinical trials of patients with T2DM receiving metformin compared with another active glucose-lowering treatment or placebo in which a microvascular outcome was assessed. The risk of bias was assessed using the Cochrane Risk of Bias tool. Microvascular complications included kidney-related outcomes, retinopathy, and peripheral neuropathy. An inverse-weighted variance random-effect meta-analysis was performed to estimate drugs effect over microvascular disease. PROSPERO (CRD42019120365). RESULTS: Nineteen RCTs (n = 18,181) were included. Metformin increased estimated glomerular filtration rate (eGFR) by a mean difference (MD) of 1.08 (95% CI 0.84 to 1.33 ml/min/1.73 m2) after 24 weeks. No effect was found on urinary albumin-creatinine ratio, serum creatinine, and end-stage kidney disease; Patient-important outcomes regarding kidney disease, retinal outcomes, peripheral neuropathy or quality of life were not assessed by any of the included studies and could not be analyzed. CONCLUSIONS: There is no evidence of clinically significant beneficial effect of metformin therapy as compared to other glucose-lowering medications or placebo on the examined microvascular complications.

Adrenal functional reserve in the full spectrum of chronic kidney disease.

BACKGROUND: Altered cortisol levels have been associated with an increase in mortality and a decrease in health-related quality of life in patients with chronic kidney disease (CKD); however, adrenal response to adrenocorticotropic hormone (ACTH) stimulation test has not been evaluated in patients with stage 3a to 5 CKD with and without renal replacement therapy (RRT). OBJECTIVE: To evaluate adrenal function in patients with CKD. MATERIALS AND METHODS: Adults with CKD underwent a low-dose cosyntropin stimulation test (1 µg synthetic ACTH), with serum cortisol levels being measured at 0, +30 and +60 minutes post-test. RESULTS: Sixty participants with stage 3, 4 and 5 CKD (with and without RRT) were included. None of the patients had adrenal insufficiency (AI). The correlation observed between cortisol concentration at baseline and 30 minutes and 1 hour after stimulation and glomerular filtration rate (GFR) was negative and statistically significant (r: -0.39 [p = 0.002], r: -0.363 [p = 0.004], r: -0.4 [p = 0.002], respectively). CONCLUSION: Since CKD early stages, cortisol levels increase as GFR decreases. Therefore, we conclude that systematic screening for AI is not necessary in CKD patients.

ANTECEDENTES: Niveles alterados de cortisol se han asociado a un incremento en la mortalidad y disminución en la calidad de vida en pacientes con enfermedad renal crónica (ERC), sin embargo, la respuesta adrenal a la prueba de estimulación con adrenocorticotropina (ACTH) no ha sido evaluada en pacientes con ERC etapas 3a a 5 con y sin terapia de reemplazo renal (TRR). OBJETIVO: Evaluar la función adrenal de pacientes con ERC. MATERIALES Y MÉTODOS: Adultos con ERC se sometieron a una prueba de estimulación con cosintropina a dosis baja (1 mg de ACTH sintética) y se midieron los niveles séricos de cortisol a los 0, +30 y +60 minutos postestimulación. RESULTADOS: 60 participantes con ERC en etapas 3, 4 y 5 (con y sin TRR) fueron incluidos. Ninguno de los pacientes presentó insuficiencia adrenal (IA). La correlación observada entre la concentración basal, a los 30 minutos y 1 hora de cortisol postestimulación y la tasa de filtrado glomerular (TFG) fue negativa y estadísticamente significativa (r: ­0.39 [p = 0.002], r: ­0.363 [p = 0.004], r: ­0.4 [p = 0.002], respectivamente). CONCLUSIÓN: Desde etapas tempranas de la ERC los niveles de cortisol se incrementan a medida que la TFG disminuye. Concluimos que no es necesario un tamizaje sistemático para detectar IA en pacientes con ERC.