Exenatide in obesity with accelerated gastric emptying: a randomized, pharmacodynamics study

Abstract

Obesity is associated with differences in satiety, gastric emptying (GE), gastric volume, and psychological traits. Exenatide, a short-acting glucagon-like peptide 1 (GLP-1) receptor agonist, is associated with variable weight loss. We compared the effects of exenatide, 5 μg, and placebo SQ, twice daily for 30 days on GE of solids and liquids (scintigraphy), satiety (ad libitum buffet meal), satiation (nutrient drink test, maximum tolerated volume [MTV]), and weight loss in 20 participants with documented accelerated GE of solids (T1/2 < 90 min). Exenatide delayed GE of solids (T1/2 [Δ] 86 min relative to placebo, P < 0.001) and reduced calorie intake at buffet meal ([Δ] 129 kcal compared to placebo). Median weight loss was -0.95 kg (IQR -0.7 to -2.1) for exenatide and -0.55 kg (0.3 to -2.1) for placebo (P = 0.23); 80% of exenatide group had documented reduction in weight. In the exenatide treatment group, there was an inverse correlation between gastric emptying T1/2 and MTV (R = -0.548, P = 0.089). The univariate association of weight change with posttreatment MTV was borderline (Rs = 0.43, P = 0.06); in the multiple regression model, posttreatment MTV was associated with weight change (P = 0.047). The effect of the short-acting GLP-1 receptor agonist, exenatide, on GE is associated with the change in food intake, and the latter impacts weight loss in response to exenatide treatment.

Keywords: Glucagon‐like peptide 1; pharmacogenomics; satiation.

Figure 1

Consort diagram.

Figure 2

Effect of exenatide on gastric emptying in obese patients with previously documented accelerated gastric emptying (P < 0.001 for both [A] gastric emptying proportion at 1 h and [B] gastric emptying T_1/2). Data show median, IQR, and range. (C) Each individual’s gastric emptying measurements at prior study on no treatment (“baseline”) and on treatment in the current study are plotted. (D) The rate of gastric emptying per group. (E) An illustrative scintigraphic image of gastric emptying at 3 h in placebo versus exenatide, with stomach area demarcated in yellow.

Figure 3

Effect of exenatide on body weight. Data shown are medians (IQR).

Figure 4

(A) Relationship of gastric emptying and maximum tolerated volume (MTV) in patients treated with exenatide (−r = −0.548; P = 0.089). (B) In a multiple regression model, including gastric emptying and satiation parameters, posttreatment MTV was modestly associated with weight change (P = 0.047).