Effect of exenatide on splanchnic and peripheral glucose metabolism in type 2 diabetic subjects.
Level 4 - case-series / case-control
Uncontrolled before-and-after mechanistic physiological study
PubMed 21411546 · doi:10.1210/jc.2010-2146
What was done
Seventeen patients with type 2 diabetes mellitus (mean age 44 yr, 7 females, 10 males, mean BMI 33.6 kg/m², HbA1c 7.9%) underwent a 6-hour mixed-meal double-tracer study ([1-¹⁴C]glucose orally and [3-³H]glucose intravenously) before and after 2 weeks of exenatide. In protocol I (n = 12), exenatide was not administered on the morning of the repeat meal. In protocol II (n = 5), exenatide was given the morning of the repeat meal. Endpoints included total and oral glucose appearance rates (RaT and RaO), endogenous glucose production (EGP), splanchnic glucose uptake, gastric emptying (acetaminophen AUC), and hepatic insulin resistance.
What was found
In protocol I (n = 12), fasting plasma glucose decreased from 10.2 to 7.6 mm (P < 0.05) and mean postmeal glucose decreased from 13.2 to 11.3 mm (P < 0.05). Basal EGP decreased from 13.9 to 10.8 μmol/kg · min (P < 0.05) and hepatic insulin resistance declined (P < 0.05). Fasting and meal-stimulated plasma insulin, glucagon, RaO, gastric emptying, and splanchnic glucose uptake did not change significantly. In protocol II (n = 5), fasting plasma glucose decreased from 11.1 to 8.9 mm (P < 0.05) and mean postmeal glucose decreased from 14.2 to 10.1 mm (P < 0.05). Basal EGP decreased from 13.4 to 10.7 μmol/kg · min (P = 0.05). Fasting and meal-stimulated insulin and glucagon did not change significantly. RaT and RaO decreased markedly from 0 to 180 min after meal ingestion.
Why it matters
This study demonstrates that exenatide lowers fasting glucose by suppressing basal hepatic glucose production and reduces postprandial hyperglycemia by acutely delaying the systemic appearance of oral glucose.
Limits
The study is limited by a small sample size (n = 17 total, with only 5 in protocol II), absence of a randomized control or placebo group, and a short 2-week observation window.
Cited by
- partial GLP-1 receptor agonist medications slow gastric emptying, thereby reducing post-meal glucose spikes and significantly increasing insulin sensitivity.