The role of glucagon-like peptide 1 in the postprandial effects of metformin in type 2 diabetes: a randomized crossover trial
Authors' conclusion
Using GLP-1R antagonization, we could not detect GLP-1-mediated postprandial glucose-lowering effect of metformin in individuals with T2D. We show that 2 weeks of metformin treatment increases fasting plasma GLP-1, which may contribute to metformin's beneficial effect on fasting plasma glucose in T2D.
Study context
- Population
- Individuals with T2D (median HbA1c 50 mmol/mol [6.7%], BMI 30.1 kg/m², age 71 years)crossover
- Participants
- 15 individuals
- Comparison
- Metformin vs placebo for 14 days, each with mixed meal tests under GLP-1R antagonist exendin(9-39)NH2 or saline infusion
- Metforminn = 15
- Placebon = 15reference
- Primary endpoint
- Contribution of postprandial GLP-1-mediated effects to the glucose-lowering effect of metformin (metformin-induced improvement in postprandial glucose tolerance with vs without GLP-1R antagonization)
- Follow-up
- 4 h mixed meal tests after 14 days of treatment
Methodological detailsrandomized, placebo-controlled, double-blind, exendin(9-39)NH2 vs saline infusion during mixed meal tests, Each 14-day treatment period preceded by 14 days without glucose-lowering medicine; two 4 h mixed meal tests in randomized order, >24 h apart, with IV exendin(9-39)NH2 or saline
- Randomized
- Placebo-controlled
- Double-blind
- Exendin(9-39)NH2 vs saline infusion during mixed meal tests
- Each 14-day treatment period preceded by 14 days without glucose-lowering medicine; two 4 h mixed meal tests in randomized order, >24 h apart, with IV exendin(9-39)NH2 or saline
Primary result
As reported in the abstract
Metformin-induced improvement in postprandial glucose tolerance unaffected by GLP-1R antagonization
82
MD, mmol/L × min, 95% CI −6564–170
Postprandial plasma glucose excursions lowered by metformin vs placebo during saline infusion
186
MD, mmol/L × min, 95% CI 64–307
Postprandial plasma glucose excursions lowered by metformin vs placebo during exendin(9-39)NH2 infusion
268
MD, mmol/L × min, 95% CI 108–427
Further findings
| Outcome | MD (mmol/L × min) (95% CI) | |
|---|---|---|
| Fasting plasma glucose · after 14 days | 1.4 (0.8–2.0) | |
| Postprandial plasma glucose excursions during saline infusion · 4 h mixed meal test | 186 (64–307) | |
| Postprandial plasma glucose excursions during exendin(9-39)NH2 infusion · 4 h mixed meal test | 268 (108–427) | |
| −2000200400600Difference, mmol/L × min (linear scale) |
| Outcome | MD (pmol/L × min) (95% CI) | |
|---|---|---|
| Fasting plasma GLP-1 · after 14 days | 1.7 (0.39–2.9) | |
| −2024Difference, pmol/L × min (linear scale) |
| Outcome | MD (pmol/L × min) (95% CI) |
|---|---|
| Postprandial GLP-1 responses · 4 h mixed meal testMetformin did not affect postprandial GLP-1 responses | 820 (−1750-111) |
Original publication
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