Sustained influence of metformin therapy on circulating glucagon‐like peptide‐1 levels in individuals with and without type 2 diabetes
Year: 2016
Type: article
Abstract: AIMS: To investigate, in the Carotid Atherosclerosis: Metformin for Insulin Resistance (CAMERA) trial (NCT00723307), whether the influence of metformin on the glucagon-like peptide (GLP)-1 axis in individuals with and without type 2 diabetes (T2DM) is sustained and related to changes in glycaemia or weight, and to investigate basal and post-meal GLP-1 levels in patients with T2DM in the cross-sectional Diabetes Research on Patient Stratification (DIRECT) study. MATERIALS AND METHODS: CAMERA was a double-blind randomized placebo-controlled trial of metformin in 173 participants without diabetes. Using 6-monthly fasted total GLP-1 levels over 18 months, we evaluated metformin's effect on total GLP-1 with repeated-measures analysis and analysis of covariance. In the DIRECT study, we examined active and total fasting and 60-minute post-meal GLP-1 levels in 775 people recently diagnosed with T2DM treated with metformin or diet, using Student's t-tests and linear regression. RESULTS: In CAMERA, metformin increased total GLP-1 at 6 (+20.7%, 95% confidence interval [CI] 4.7-39.0), 12 (+26.7%, 95% CI 10.3-45.6) and 18 months (+18.7%, 95% CI 3.8-35.7), an overall increase of 23.4% (95% CI 11.2-36.9; P < .0001) vs placebo. Adjustment for changes in glycaemia and adiposity, individually or combined, did not attenuate this effect. In the DIRECT study, metformin was associated with higher fasting active (39.1%, 95% CI 21.3-56.4) and total GLP-1 (14.1%, 95% CI 1.2-25.9) but not post-meal incremental GLP-1. These changes were independent of potential confounders including age, sex, adiposity and glycated haemoglobin. CONCLUSIONS: In people without diabetes, metformin increases total GLP-1 in a sustained manner and independently of changes in weight or glycaemia. Metformin-treated patients with T2DM also have higher fasted GLP-1 levels, independently of weight and glycaemia.
Source: Diabetes Obesity and Metabolism
DOI: 10.1111/dom.12826
Authors: David Preiss, Adem Dawed, Paul Welsh, Alison Heggie, Angus G. Jones, Jacqueline Dekker, Robert Koivula, Tue H. Hansen, Caitlin Stewart, Rury R. Holman, Paul W. Franks, Mark Walker, Ewan R. Pearson, Naveed Sattar
Institutions: University of Oxford, MRC Population Health Research Unit, University of Dundee, University of Glasgow, Newcastle University, University of Exeter, NIHR Exeter Clinical Research Facility, Amsterdam UMC Location Vrije Universiteit Amsterdam, Lund University, University of Copenhagen, Novo Nordisk Foundation, Novo Nordisk Foundation Center for Basic Metabolic Research
Language: English
Subfield: Endocrinology, Diabetes and Metabolism
Field: Medicine
Domain: Health Sciences
Open Access status: green
Funders: Bristol-Myers Squibb, Eli Lilly and Company, AstraZeneca, Bayer, Merck, Novartis, Sanofi, Boehringer Ingelheim, Wellcome Trust, European Federation of Pharmaceutical Industries and Associations, National Institute for Health and Care Research, Chief Scientist Office, European Commission, Novo Nordisk, Innovative Medicines Initiative, Merck Sharp and Dohme, Seventh Framework Programme
Awards: G1073258374, G119964413, DIabetes REsearCh on patient sTratification, G297885364, G3207356259, G393177772, G5702163051, G5943380856, Stratified medicine in Type 2 diabetes: Insights from the study of drug response., G7493495844, Integrating clinical features and biomarkers to improve diabetes classification and treatment in young adults
OpenAlex ID: W2549087520