Effect of the glucagon-like peptide-1 analogue liraglutide versus placebo treatment on circulating proglucagon-derived peptides that mediate improvements in body weight, insulin secretion and action: A randomized controlled trial.
Level 2 - randomized trial
Individual randomized controlled trial
PubMed 33140542 · doi:10.1111/dom.14242
What was done
Adults who were overweight or obese (BMI 27–40 kg/m²) with prediabetes were randomized to liraglutide (1.8 mg/day; n = 16) or placebo (n = 19) for 14 weeks. Specific assays during a mixed meal tolerance test (MMTT) measured exogenous liraglutide (GLP-1A), endogenous GLP-1 (GLP-1E), and five other proglucagon-derived peptides (PGDPs: GLP-2, glucagon, oxyntomodulin, glicentin, and major proglucagon fragment) at baseline and week 14. Steady-state plasma glucose (SSPG) for insulin resistance, insulin secretion rate (ISR), and glucose area-under-the-curve (AUC) were evaluated.
What was found
Compared to placebo, liraglutide significantly improved metabolic parameters (all P ≤ .004): weight decreased by a mean of -3.6% (95% CI [-5.2% to -2.1%]), SSPG decreased by -32% (95% CI [-43% to -22%]), glucose AUC decreased by -7.0% (95% CI [-11.5% to -2.5%]), and ISR AUC increased by 30% (95% CI [16% to 44%]). GLP-1A AUC correlated linearly with % weight loss (r = -0.54), SSPG reduction (r = -0.59), and ISR AUC increase (r = 0.51; all P ≤ .04). Liraglutide significantly reduced endogenous GLP-1E AUC (median 13.1 vs. 24.2 pmol/L × 8 hours at baseline) and the other five PGDPs (P ≤ .005). Decreases in intestinal PGDPs were independent of weight loss, whereas pancreatic alpha-cell PGDPs were weight loss-dependent.
Why it matters
This trial shows that circulating liraglutide levels linearly predict therapeutic metabolic improvements while downregulating endogenous proglucagon-derived peptides through distinct intestinal and pancreatic mechanisms.
Limits
The sample size was very small (35 participants analyzed), limiting statistical power and subgroup precision. The study was conducted exclusively in overweight/obese adults with prediabetes over a short 14-week duration and tested a single dose of liraglutide (1.8 mg/day).
Cited by
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