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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; Dawed, Adem; Welsh, Paul; Heggie, Alison; Jones, Angus G.; Dekker, Jacqueline; Koivula, Robert LU ; Hansen, Tue H.; Stewart, Caitlin and Holman, Rury R., et al. (2017) In Diabetes, Obesity and Metabolism 19(3). p.356-363
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 18months, we evaluated metformin's effect on total GLP-1 with repeated-measures analysis and... (More)

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.

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Contribution to journal
publication status
published
subject
keywords
GLP-1, Antidiabetic drug, Metformin
in
Diabetes, Obesity and Metabolism
volume
19
issue
3
pages
356 - 363
publisher
Wiley-Blackwell
external identifiers
  • scopus:85007557014
  • wos:000394785200006
ISSN
1462-8902
DOI
10.1111/dom.12826
language
English
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yes
id
5491c345-cfe5-433e-bb43-62e102bfad20
date added to LUP
2017-01-20 13:36:14
date last changed
2018-07-15 04:37:15
@article{5491c345-cfe5-433e-bb43-62e102bfad20,
  abstract     = {<p>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 &lt;.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.</p>},
  author       = {Preiss, David and Dawed, Adem and Welsh, Paul and Heggie, Alison and Jones, Angus G. and Dekker, Jacqueline and Koivula, Robert and Hansen, Tue H. and Stewart, Caitlin and Holman, Rury R. and Franks, Paul W. and Walker, Mark and Pearson, Ewan R. and Sattar, Naveed},
  issn         = {1462-8902},
  keyword      = {GLP-1,Antidiabetic drug,Metformin},
  language     = {eng},
  number       = {3},
  pages        = {356--363},
  publisher    = {Wiley-Blackwell},
  series       = {Diabetes, Obesity and Metabolism},
  title        = {Sustained influence of metformin therapy on circulating glucagon-like peptide-1 levels in individuals with and without type 2 diabetes},
  url          = {http://dx.doi.org/10.1111/dom.12826},
  volume       = {19},
  year         = {2017},
}