Reductions in Insulin Resistance are Mediated Primarily via Weight Loss in Subjects With Type 2 Diabetes on Semaglutide.

Autor:	Fonseca VA; Health Sciences Center, Tulane University, New Orleans, Louisiana., Capehorn MS; Rotherham Institute for Obesity, Clifton Medical Centre, Rotherham, United Kingdom., Garg SK; Barbara Davis Center for Diabetes, University of Colorado Denver, Aurora, Colorado., Jódar Gimeno E; Hospital Universitario Quirón Salud Madrid, Universidad Europea de Madrid, Madrid, Spain., Hansen OH; Novo Nordisk A/S, Søborg, Denmark., Holst AG; Novo Nordisk A/S, Søborg, Denmark., Nayak G; Novo Nordisk A/S, Søborg, Denmark., Seufert J; University of Freiburg Medical Center, Medical Faculty, University of Freiburg, Freiburg, Germany.
Jazyk:	angličtina
Zdroj:	The Journal of clinical endocrinology and metabolism [J Clin Endocrinol Metab] 2019 Sep 01; Vol. 104 (9), pp. 4078-4086.
DOI:	10.1210/jc.2018-02685
Abstrakt:	Context: Semaglutide, a once-weekly glucagon-like peptide-1 analog approved for use in patients with type 2 diabetes (T2D), demonstrated superior body weight (BW) reductions and decreased insulin resistance (IR) vs comparators across the Semaglutide Unabated Sustainability in Treatment of Type 2 Diabetes (SUSTAIN) 1-3 clinical trials. Objective: To investigate the relationship between IR and BW across the SUSTAIN 1-3 trials. Design: Post hoc analysis of the SUSTAIN 1-3 trials. Setting: Three hundred and eleven sites in 30 countries. Patients or Other Participants: 2432 subjects with T2D. Interventions: Semaglutide 0.5 or 1.0 mg, placebo or active comparator (sitagliptin 100 mg, exenatide extended release 2.0 mg). Main Outcome Measure: To assess the extent of the effect on IR that is mediated (indirect effect) and not mediated (direct effect) by the effect on BW. Results: Across SUSTAIN 1-3, mean BW was significantly reduced with semaglutide 0.5 mg (3.7 kg to 4.3 kg; P < 0.0001) and semaglutide 1.0 mg (4.5 kg to 6.1 kg; P < 0.0001) vs comparators (1.0 kg to 1.9 kg). There were greater reductions in IR with semaglutide 0.5 mg (27% to 36%) and semaglutide 1.0 mg (32% to 46%) vs comparators (17% to 28%). Greater reductions in BW were generally associated with greater decreases in IR. The effect on IR was primarily mediated by weight loss (70% to 80% and 34% to 94%, for semaglutide 0.5 mg and 1.0 mg, respectively, vs comparator). Conclusions: Semaglutide consistently reduced BW and IR in subjects with T2D in SUSTAIN 1-3. In this analysis, IR improvement was positively associated with, and primarily mediated by, the effect of semaglutide on BW. (Copyright © 2019 Endocrine Society.)
Databáze:	MEDLINE
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