Dados do Trabalho

Título

HbA1c reduction with tirzepatide in people with type 2 diabetes: A mediation analysis using body weight loss as a factor

Resumo

Introduction Tirzepatide (TZP) is a first-in-class once weekly glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist that is approved for treatment of people with type 2 diabetes and under investigation for chronic weight management. Objective In the SURPASS-1, -2 and -5 clinical studies, TZP 5, 10 and 15 mg demonstrated significant improvements in HbA1c and body weight at week 40 vs placebo or semaglutide 1 mg. Post hoc mediation analyses were conducted to evaluate weight loss-dependent (WL-D) and weight loss-independent (WL-IND) effects of tirzepatide 5, 10, or 15 mg on change in HbA1c from baseline to week 40 in SURPASS-1, -2 and -5.  Methods Analyses were done by study, based on data from participants while on assigned treatment without rescue medication for persistent hyperglycaemia. Comparators were placebo (SURPASS-1, SURPASS-5) and semaglutide 1 mg once weekly (SURPASS-2) and excluded the insulin-controlled studies SURPASS-3 and -4. Weight loss dependent and Weight loss independent effects on HbA1c at week 40 were estimated using the product method for mediation analysis, adjusted for baseline HbA1c and study-specific stratification factors. Results The difference in HbA1c change from baseline at 40 weeks (total effect) between TZP and comparator group was -19.0 to -1.9 mmol/mol (-1.7 to -0.2%) (TZP 5 mg), -19.1 to -4.5 mmol/mol (-1.8 to -0.4%) (TZP 10 mg) and -20.0 to -5.1 mmol/mol (-1.8 to -0.5%) (TZP 15 mg).  In the placebo-controlled trials, 12% to 27% of the difference in HbA1c change between TZP dose arms and placebo was estimated as being mediated through weight loss when given as monotherapy (SURPASS-1), and 25% to 45% when on the background of insulin with or without metformin (SURPASS-5). When compared to semaglutide (SURPASS-2, add-on to metformin), 54 to 71% of the difference in HbA1c change between TZP dose arms and semaglutide, was estimated as being mediated through weight loss. Conclusion  In conclusion, the TZP-induced HbA1c reductions from baseline, compared with placebo or semaglutide, were mediated through both WL-D and WL-IND effects.   © 2023 International Society for Pharmacoeconomics and Outcomes Research. Reused with permission. This abstract was accepted and previously presented at the ISPOR Europe 2023 conference; Copenhagen, Denmark. All rights reserved.        

Palavras Chave

Tirzepatida; Diabetes tipo 2