Exposure-response analysis for evaluation of semaglutide dose levels in type 2 diabetes

Diabetes, Obesity & Metabolism
K C PetriRune Viig Overgaard

Abstract

To evaluate dose levels for semaglutide, a glucagon-like peptide-1 analogue approved for the treatment of type 2 diabetes, by examining the effects of demographic factors on efficacy and safety in an exposure-response analysis. We analysed data from 1552 adults from four randomized phase III trials of 30 to 56 weeks' duration, investigating once-weekly semaglutide doses 0.5 and 1.0 mg. Exposure-response relationships were investigated using graphical and model-based techniques to assess the two dose levels and subgroups with the highest and lowest exposure and response. The population had the following demographic characteristics: baseline mean age between 53.2 and 58.4 years, glycated haemoglobin (HbA1c) between 64 and 67 mmol/mol (8.0% and 8.3%), body weight between 71.3 and 96.2 kg, and diabetes duration between 4.2 and 8.9 years. Exposure-response analysis showed a clear HbA1c and weight reduction across exposures after 30 weeks, irrespective of baseline values. The exposure-response for HbA1c was influenced by baseline HbA1c, and body weight exposure-response was influenced by sex, with limited impact of other factors. Analyses for relevant subgroups of baseline body weight, baseline HbA1c and sex indicated clinically rele...Continue Reading

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Citations

Feb 16, 2019·Obesity Reviews : an Official Journal of the International Association for the Study of Obesity·Georgios A ChristouDimitrios N Kiortsis
Feb 23, 2019·Diabetes Therapy : Research, Treatment and Education of Diabetes and Related Disorders·Rune V OvergaardSteen H Ingwersen
Jul 31, 2020·JCI Insight·Francis S WillardKyle W Sloop
May 11, 2021·Clinical Pharmacokinetics·Rune V OvergaardRasmus Juul Kildemoes
Jul 22, 2021·Diabetes, Obesity & Metabolism·Richard E PratleyNino Miresashvili

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Clinical Trials Mentioned

NCT02054897
NCT01930188
NCT01885208
NCT02207374

Software Mentioned

Revolution Analytics
R

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