Effects of semaglutide on beta cell function and glycaemic control in participants with type 2 diabetes: a randomised, double-blind, placebo-controlled trial.
Level 2 - randomized trial
Individual randomized controlled trial
PubMed 28526920 · doi:10.1007/s00125-017-4289-0
What was done
In a single-centre, double-blind, parallel-group trial in Germany, 75 adults aged 18–64 with type 2 diabetes (HbA1c 6.5–9.0%, BMI 20.0–35.0 kg/m², on diet/exercise or metformin monotherapy) were randomized 1:1 to once-weekly subcutaneous semaglutide (dose-escalated to 1.0 mg) or placebo for 12 weeks. Co-primary endpoints were changes from baseline to week 12 in first-phase (AUC 0–10 min) and second-phase (AUC 10–120 min) insulin secretion measured via intravenous glucose tolerance test (IVGTT). Secondary assessments included an arginine stimulation test (AST), a 24-hour meal stimulation test, and a graded glucose infusion test (GGIT) benchmarked against untreated healthy controls.
What was found
Thirty-seven participants received semaglutide and 38 received placebo. Following IVGTT, semaglutide significantly increased first-phase insulin secretion (estimated treatment ratio 3.02, 95% CI [2.53, 3.60]; p < 0.0001) and second-phase insulin secretion (estimated treatment ratio 2.10, 95% CI [1.86, 2.37]; p < 0.0001). The 24-hour meal test showed significant reductions in fasting, postprandial, and overall glucose and glucagon AUC (p < 0.0001). Semaglutide increased maximal insulin capacity on AST and elevated insulin secretion rates during GGIT to levels comparable to healthy controls.
Why it matters
This trial demonstrates that semaglutide directly restores both phases of glucose-dependent insulin secretion and suppresses glucagon, elevating insulin secretion rates close to non-diabetic levels in patients with type 2 diabetes.
Limits
The trial had a small sample size (n = 75), short duration (12 weeks), single-centre design, and tested a population with mild-to-moderate diabetes on metformin or lifestyle intervention only. The study was funded by the manufacturer.
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