Sustained influence of metformin therapy on circulating glucagon-like peptide-1 levels in individuals with and without type 2 diabetes.
Preiss. David D; Dawed. Adem A; Welsh. Paul P; Heggie. Alison A; Jones. Angus G AG; Dekker. Jacqueline J; Koivula. Robert R; Hansen. Tue H TH; Stewart. Caitlin C; Holman. Rury R RR; Franks. Paul W PW; Walker. Mark M; Pearson. Ewan R ER; Sattar. Naveed N
Key Findings
- Metformin increased total fasting GLP-1 by ~20‑27% at 6‑12 months and stayed elevated at 18 months in non‑diabetics.
- The GLP-1 rise was independent of changes in weight, blood sugar, or other metabolic measures.
- In newly diagnosed diabetics, metformin users had higher fasting active and total GLP-1 compared to diet‑only patients, without affecting post‑meal GLP-1 spikes.
Practical Outcomes
- For biohackers aiming to boost GLP-1 for metabolic health or longevity, a standard metformin dose (as used in clinical trials) can be a reliable way to raise fasting GLP-1 long‑term. This benefit appears regardless of weight loss, so it can be added to protocols focused on insulin sensitivity, appetite control, or anti‑aging, even if you’re not targeting glucose reduction directly.
Summary
Taking metformin regularly raises your fasting GLP-1 hormone levels and keeps them higher for at least a year and a half, even if you don’t lose weight or change your blood sugar. This effect shows up in people without diabetes and also in newly diagnosed diabetics, and it’s not just a short‑term spike after a meal.
Abstract
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. 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. 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. 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.
Study Information
pubmed
2016
2016-12-28T00:00:00.000Z
10.1111/dom.12826
53
30