The online version of this article (doi:10.1007/s00125-017-4289-0) contains peer-reviewed but unedited supplementary material, which is available to authorised users.
Semaglutide is a glucagon-like peptide-1 analogue in development for the treatment of type 2 diabetes. Its effects on first- and second-phase insulin secretion and other measures of beta cell function and glycaemic control were assessed.
In this single-centre, double-blind, placebo-controlled, parallel-group trial, conducted at the Profil Institut für Stoffwechselforschung, Germany, 75 adult (aged 18–64 years) participants with type 2 diabetes (eligibility: HbA1c of 6.5–9.0% (47.5–74.9 mmol/mol); BMI 20.0–35.0 kg/m2; and treatment with diet and exercise and/or metformin monotherapy with a dose unchanged in the 30 days prior to screening) were randomised (1:1) to once-weekly s.c. semaglutide 1.0 mg (0.25, 0.5, 1.0 mg escalated) or placebo for 12 weeks. Co-primary endpoints were changes from baseline to end of treatment in the first (AUC0–10 min) and second (AUC10–120 min) insulin secretion phases, as measured by the IVGTT. An arginine stimulation test (AST) and a 24 h meal stimulation test were also conducted. A graded glucose infusion test (GGIT) assessed insulin secretion rate (ISR) in treated participants and a group of untreated healthy participants. Safety endpoints were also assessed.
In total, 37 participants received semaglutide and 38 received placebo. Following IVGTT, for insulin, both AUC0−10min and AUC10−120min were significantly increased with semaglutide (estimated treatment ratio [95% CI] 3.02 [2.53, 3.60] and 2.10 [1.86, 2.37], respectively; p < 0.0001). The 24 h meal test showed reduced fasting, postprandial and overall (AUC0–24h) glucose and glucagon responses with semaglutide (p < 0.0001). The AST showed that maximal insulin capacity increased following semaglutide treatment. During GGIT, semaglutide significantly increased ISR to levels similar to those in healthy participants. Semaglutide was well tolerated.
Twelve weeks of once-weekly treatment with semaglutide significantly improved beta cell function and glycaemic control in participants with type 2 diabetes.
The study was funded by Novo Nordisk A/S.
ESM (PDF 74 kb)125_2017_4289_MOESM1_ESM.pdf
UK Prospective Diabetes Study Group (1995) U.K. Prospective Diabetes Study 16. Overview of 6 years’ therapy of type II diabetes: a progressive disease. Diabetes 44:1249–1258
Garber AJ (2011) Incretin effects on β-cell function, replication, and mass: the human perspective. Diabetes Care 34:S258–S263
Degn KB, Juhl CB, Sturis J et al (2004) One week’s treatment with the long-acting glucagon-like peptide 1 derivative liraglutide (NN2211) markedly improves 24-h glycemia and alpha- and beta-cell function and reduces endogenous glucose release in patients with type 2 diabetes. Diabetes 53:1187–1194 CrossRefPubMed
Hjerpsted J, Brooks A, Flint A, Kvist T, Blundell J (2016) Semaglutide improves postprandial glucose and lipid metabolism and delays first-hour gastric emptying in subjects with obesity. American Diabetes Association 76th Scientific Sessions, New Orleans, LA, USA, 10–14 June, 2016. Abstract 1046-P
European Agency for the Evaluation of Medicinal Products. International Conference on Harmonisation—World Health Organization Guideline for good clinical practice ICH Harmonised tripartite guideline good clinical practice www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2009/09/WC500002874.pdf. Accessed 10 February 2017
World Medical Association (2013) World Medical Association Declaration of Helsinki: ethical principles for medical research involving human subjects. JAMA 310:2191–2194
American Diabetes Association Workgroup on Hypoglycemia (2005) Defining and reporting hypoglycemia in diabetes: a report from the American Diabetes Association Workgroup on Hypoglycemia. Diabetes Care 28:1245–1249 CrossRef
Hovorka R, Soons PA, Young MA (1996) ISEC: a program to calculate insulin secretion. Comput Methods Prog Biomed 50:253–264 CrossRef
Ho TP, Zhao X, Courville AB et al (2015) Effects of a 12-month moderate weight loss intervention on insulin sensitivity and inflammation status in nondiabetic overweight and obese subjects. Horm Metab Res 47:289–296 PubMed
De Tata V (2014) Age-related impairment of pancreatic Beta-cell function: pathophysiological and cellular mechanisms. Front Endocrinol (Lausanne) 5:138
Standl E (2007) The importance of beta-cell management in type 2 diabetes. Int J Clin Pract 61(Suppl 153):10–19 CrossRef
Zheng J, Chen T, Zhu Y et al (2015) Liraglutide prevents fast weight gain and beta-cell dysfunction in male catch-up growth rats. Exp Biol Med (Maywood) 240:1165–1176 CrossRef
Ahmann AJ, Capehorn M, Charpentier G et al (2016) Efficacy and safety of once-weekly semaglutide vs exenatide ER after 56 weeks in subjects with type 2 diabetes (SUSTAIN 3). Diabetologia 59:S76 (Abstract)
Marre M, Shaw J, Brändle M et al (2009) Liraglutide, a once-daily human GLP-1 analogue, added to a sulphonylurea over 26 weeks produces greater improvements in glycaemic and weight control compared with adding rosiglitazone or placebo in subjects with type 2 diabetes (LEAD-1 SU). Diabet Med 26:268–278 CrossRefPubMedPubMedCentral
- Effects of semaglutide on beta cell function and glycaemic control in participants with type 2 diabetes: a randomised, double-blind, placebo-controlled trial
Jacob B. Jacobsen
Mads B. Axelsen
- Springer Berlin Heidelberg
Neu im Fachgebiet Innere Medizin
Meistgelesene Bücher aus der Inneren Medizin
e.Med Kampagnen-Visual, Mail Icon II