Effects of Sustained Treatment With Lixisenatide on Gastric Emptying and Postprandial Glucose Metabolism in Type 2 Diabetes: A Randomized Controlled Trial.
Level 2 - randomized trial
Individual randomized controlled trial
PubMed 32471908 · doi:10.2337/dc20-0190
What was done
Thirty patients with metformin-treated type 2 diabetes were randomized in a double-blind, parallel-group trial to receive either daily subcutaneous lixisenatide (20 μg) or placebo for 8 weeks. Gastric emptying was quantified with scintigraphy and glucose kinetics were measured using a dual-tracer technique after ingestion of a 75-g oral glucose drink before and after the 8-week treatment period.
What was found
Lixisenatide significantly increased gastric retention of the glucose drink compared to placebo (ratio of adjusted geometric means for AUC over 240 min: 2.19, 95% CI 1.82–2.64, P < 0.001). This was accompanied by reductions in the systemic appearance rate of oral glucose (P < 0.001) and incremental AUC for blood glucose (P < 0.001). Lixisenatide also suppressed glucagon (P = 0.003) and insulin (P = 0.032) over 120 min post-drink, while endogenous glucose production was not suppressed. Postprandial glucose reduction over 240 min was strongly related to the magnitude of gastric emptying slowing (r = -0.74, P = 0.002) and baseline emptying rate (r = 0.52, P = 0.048), but unrelated to β-cell glucose sensitivity.
Why it matters
Continuous exposure to GLP-1 receptor agonists often causes tachyphylaxis for gastric slowing; these findings demonstrate that the short-acting GLP-1 receptor agonist lixisenatide maintains its gastric-emptying delay and postprandial glucose-lowering effects across 8 weeks of treatment.
Limits
The sample size was small (n = 30), follow-up was limited to 8 weeks, and testing evaluated a 75-g liquid glucose drink rather than standardized solid mixed meals. Outcomes beyond 8 weeks were not evaluated.
Cited by
- partial GLP-1 receptor agonist medications slow gastric emptying, thereby reducing post-meal glucose spikes and significantly increasing insulin sensitivity.