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Sustained influence of metformin therapy on circulating glucagon-like peptide-1 levels in individuals with and without type 2 diabetes

Preiss, David (författare)
University of Oxford
Dawed, Adem (författare)
University of Dundee
Welsh, Paul (författare)
University of Glasgow
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Heggie, Alison (författare)
University of Newcastle upon Tyne
Jones, Angus G. (författare)
University of Exeter
Dekker, Jacqueline (författare)
Amsterdam UMC - Vrije Universiteit Amsterdam
Koivula, Robert (författare)
Lund University,Lunds universitet,Genetisk och molekylär epidemiologi,Forskargrupper vid Lunds universitet,Genetic and Molecular Epidemiology,Lund University Research Groups
Hansen, Tue H. (författare)
University of Copenhagen
Stewart, Caitlin (författare)
University of Glasgow
Holman, Rury R. (författare)
University of Oxford
Franks, Paul W. (författare)
Lund University,Lunds universitet,Genetisk och molekylär epidemiologi,Forskargrupper vid Lunds universitet,Genetic and Molecular Epidemiology,Lund University Research Groups
Walker, Mark (författare)
University of Newcastle upon Tyne
Pearson, Ewan R. (författare)
Ninewells Hospital and Medical School
Sattar, Naveed (författare)
University of Glasgow
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 (creator_code:org_t)
2016-12-28
2017
Engelska.
Ingår i: Diabetes, Obesity and Metabolism. - : Wiley. - 1462-8902. ; 19:3, s. 356-363
  • Tidskriftsartikel (refereegranskat)
Abstract Ämnesord
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  • 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 18months, 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 18months (+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.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)

Nyckelord

GLP-1
Antidiabetic drug
Metformin

Publikations- och innehållstyp

art (ämneskategori)
ref (ämneskategori)

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