Patient-Centered Management of Type 2 Diabetes Mellitus Based on Specific Clinical Scenarios: Systematic Review, Meta-Analysis and Trial Sequential Analysis.

Pinto, Lana C; Rados, Dimitris V; Remonti, Luciana R; Viana, Luciana V; Pulz, Georgia T; Carpena, Mariana P; Borges, Roberta P; Marobin, Roberta; Beretta, Mileni V; Pedrollo, Elis F; Londero, Thizá M; Machry, Rafael; Janeczko, Lais; Moehlecke, Milene; Falcetta, Mariana R; Bauer, Andrea C; Silveiro, Sandra P; Gerchman, Fernando; Rodrigues, Ticiana C; Kramer, Caroline K; Bertoluci, Marcello C; Leitão, Cristiane B

INTRODUCTION New antihyperglycemic medications have proven cardiovascular and renal benefits in type 2 diabetes mellitus (T2DM); however, an evidence-based decision tree in specific clinical scenarios is lacking. MATERIALS AND METHODS Systematic review and meta-analysis of randomized controlled trials (RCTs) with trial sequential analysis (TSA). RCT inclusion criteria were patients with T2DM from one of these subgroups: elderly, obese, previous atherosclerotic cardiovascular disease (ASCVD), previous coronary-heart disease (CHD), previous heart failure (HF) or previous chronic kidney disease (CKD). RCTs describing those subgroups with at least 48 weeks were included. Outcomes: 3-point MACE; cardiovascular (CV) death; hospitalization due to HF; and renal outcomes. We performed direct meta-analysis with the number of events in the intervention and control groups in each subset, and the relative risk of events was calculated. RESULTS SGLT2 inhibitors (SGLT2i) and GLP-1 receptor agonists (GLP-1 RA) were the only anti-hyperglycemic agents related to reduction in CV events in different populations. For obese and elderly populations, GLP-1 RA were associated with benefits in 3-point MACE; for patients with ASCVD, both SGLT2i and GLP-1 RA had benefits in 3-point MACE, while for patients with CHD, only SGLT2i were beneficial. CONCLUSIONS SGLT2i and GLP-1 RA reduced CV events in selected populations: SGLT2i led to a reduction in events in patients with previous CHD, ASCVD and HF. GLP-1 RA led to a reduction in CV events in patients with ASCVD, elderly and patients with obesity. TSA shows that these findings are conclusive. This review opens a pathway towards evidence-based personalized treatment of T2DM.