Comparative efficacy and tolerability of currently approved incretin mimetics: A systematic analysis of placebo-controlled clinical trials

Resumo original em inglês

O que aconteceu

This study compares the therapeutic efficacy, gastrointestinal (GI) adverse event (AE) rates and the relationship between the therapeutic efficacy and GI AEs in randomized, placebo-controlled clinical trials (RCTs) of GLP-1 RAs and the dual GLP-1/GIP agonist tirzepatide.

A systematic PubMed search identified 38 phase 3 or 4 placebo-controlled RCTs of exenatide (b.i.d. and q.w.), lixisenatide, liraglutide, dulaglutide, albiglutide, semaglutide (s.c. and oral) and tirzepatide with a total of 16 660 individuals with type 2 diabetes (T2D) across 104 study arms. Changes in HbA1c, fasting plasma glucose and body weight and the proportion of GI AEs (nausea, vomiting or diarrhoea) were calculated by agent, preparation and dose. The correlation between odds ratios (ORs) for GI AEs and the magnitude of therapeutic efficacy was assessed in a linear regression analysis.

O que encontraram

Baseline characteristics were similar across studies: mean age 57 ± 10 years, diabetes duration 8 ± 6 years, body mass index (BMI) 31.9 ± 5.8 kg/m2 and HbA1c 8.2% ± 0.9%. HbA1c reductions ranged from -0.63% ± 0.03% (lixisenatide, 20 μg q.d.) to -1.79% ± 0.09% (tirzepatide, 15 mg q.w.; p < 0.0001). Weight reductions ranged from -0.75 ± 0.10 kg to -9.65 ± 0.56 kg. Despite the high variability in therapeutic efficacy, ORs for GI AEs were similar across compounds/preparations.

Por que isso importa

The magnitude of efficacy for intended therapeutic actions (HbA1c and body weight reduction) varied widely between incretin mimetic glucose-lowering agents. However, larger therapeutic efficacy was not systematically associated with higher GI AE or drug discontinuation rates, indicating better tolerability of the more effective agents/preparations.

Resumo publicado sob licença CC BY. A tradução para o português ainda não chegou a este estudo.