Comparative Effectiveness of Glucose-Lowering Drugs for Type 2 Diabetes: A Systematic Review and Network Meta-analysis.

Tsapas A, et al. · 2020

PubMed 32598218 ↗DOI: 10.7326/M20-0864Annals of internal medicine

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Revisione sistematica e network meta-analisi (certezza variabile)

La domanda

Fra i farmaci per il diabete tipo 2, quali riducono davvero mortalita ed esiti vascolari secondo il confronto complessivo delle prove?

Cosa hanno trovato

Revisione sistematica e network meta-analisi, 453 trial, 21 interventi da 9 classi (134 monoterapie, 296 add-on a metformina, 23 confronti monoterapia vs add-on). Nei pazienti drug-naive a basso rischio CV nessuna differenza fra trattamenti. Nei pazienti a basso rischio CV su base metformina (298 trial): nessuna differenza clinicamente rilevante fra trattamenti per mortalita ed esiti vascolari; insulina e specifici GLP-1 RA aggiunti a metformina danno le maggiori riduzioni di HbA1c. A rischio CV aumentato su base metformina (21 trial): semaglutide orale, empagliflozin, liraglutide, exenatide a rilascio prolungato e dapagliflozin riducono la mortalita totale; semaglutide orale, empagliflozin e liraglutide riducono anche la morte CV; ictus ridotto con semaglutide sc e dulaglutide; gli SGLT2 riducono ospedalizzazione per scompenso e malattia renale terminale. Segnali di danno: semaglutide sc (retinopatia diabetica) e canagliflozin (amputazioni). Confidenza bassa in alcune stime a basso rischio CV.

Cosa significa per te

Diabete tipo 2: se il rischio cardiovascolare e basso, nessun farmaco batte gli altri su mortalita/vasi, contano soprattutto controllo glicemico e tollerabilita. Se il rischio CV e alto, specifici GLP-1 e SGLT2 offrono benefici concreti su morte, scompenso e rene, ma con possibili segnali di danno (retinopatia, amputazioni) da pesare caso per caso. Sintesi ampia ma di certezza variabile; la scelta e del diabetologo. Non riguarda il tipo 1 (autoimmune).

Abstract (in lingua originale)

BACKGROUND: Several pharmacologic options for type 2 diabetes are available. PURPOSE: To compare benefits and harms of glucose-lowering drugs in adults with type 2 diabetes. DATA SOURCES: Several databases from inception through 18 December 2019 and ClinicalTrials.gov on 10 April 2020. STUDY SELECTION: English-language randomized trials that had at least 24 weeks of intervention and assessed the effects of glucose-lowering drugs on mortality, glycemic, and vascular outcomes. DATA EXTRACTION: Pairs of reviewers extracted data and appraised risk of bias. DATA SYNTHESIS: 453 trials assessing 21 antidiabetic interventions from 9 drug classes were included. Interventions included monotherapies (134 trials), add-on to metformin-based therapies (296 trials), and monotherapies versus add-on to metformin therapies (23 trials). There were no differences between treatments in drug-naive patients at low cardiovascular risk. Insulin regimens and specific glucagon-like peptide-1 receptor agonists (GLP-1 RAs) added to metformin-based background therapy produced the greatest reductions in hemoglobin A1c level. In patients at low cardiovascular risk receiving metformin-based background treatment (298 trials), there were no clinically meaningful differences between treatments for mortality and vascular outcomes. In patients at increased cardiovascular risk receiving metformin-based background treatment (21 trials), oral semaglutide, empagliflozin, liraglutide, extended-release exenatide, and dapagliflozin reduced all-cause mortality. Oral semaglutide, empagliflozin, and liraglutide also reduced cardiovascular death. Odds of stroke were lower with subcutaneous semaglutide and dulaglutide. Sodium-glucose cotransporter-2 (SGLT-2) inhibitors reduced heart failure hospitalization and end-stage renal disease. Subcutaneous semaglutide and canagliflozin increased diabetic retinopathy and amputation, respectively. LIMITATION: Inconsistent definitions of cardiovascular risk and low-level confidence in some estimates for patients at low cardiovascular risk. CONCLUSION: In diabetic patients at low cardiovascular risk, no treatment differs from placebo for vascular outcomes. In patients at increased cardiovascular risk receiving metformin-based background therapy, specific GLP-1 RAs and SGLT-2 inhibitors have a favorable effect on certain cardiovascular outcomes. PRIMARY FUNDING SOURCE: European Foundation for the Study of Diabetes, supported by an unrestricted educational grant from AstraZeneca. (PROSPERO: CRD42019122043).

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Come leggerlo: è uno studio scientifico peer-reviewed. Le evidenze aiutano a capire i trend, ma un singolo studio non è una prescrizione: parlane col tuo diabetologo prima di cambiare dieta o terapia.