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Randomized Controlled Trial
. 2022 Aug;30(8):1608-1620.
doi: 10.1002/oby.23481.

Effects of liraglutide on gastrointestinal functions and weight in obesity: A randomized clinical and pharmacogenomic trial

Daniel Maselli #  1 , Jessica Atieh #  1 , Matthew M Clark  2 , Deborah Eckert  1 , Ann Taylor  1 , Paula Carlson  1 , Duane D Burton  1 , Irene Busciglio  1 , W Scott Harmsen  3 , Adrian Vella  4 , Andres Acosta  1 , Michael Camilleri  1
Affiliations
Randomized Controlled Trial

Effects of liraglutide on gastrointestinal functions and weight in obesity: A randomized clinical and pharmacogenomic trial

Daniel Maselli et al. Obesity (Silver Spring). 2022 Aug.

Abstract

Objective: This study aimed to determine the effects of a long-acting glucagon-like peptide-1 (GLP-1) receptor agonist, liraglutide, and placebo subcutaneously over 16 weeks on weight and gastric functions and to evaluate associations of single-nucleotide polymorphisms in GLP1R (rs6923761) and TCF7L2 (rs7903146) with effects of liraglutide.

Methods: The study conducted a randomized, parallel-group, placebo-controlled, 16-week trial of liraglutide, escalated to 3 mg subcutaneously daily in 136 otherwise healthy adults with obesity. Weight, gastric emptying of solids (GES), gastric volumes, satiation, and body composition measured at baseline and after treatment were compared in two treatment groups using analysis of covariance.

Results: Liraglutide (n = 59) and placebo (n = 65) groups completed treatment. Relative to placebo, liraglutide increased weight loss at 5 and 16 weeks (both p < 0.05), slowed time to half GES (T1/2 ) at 5 and 16 weeks (both p < 0.001), and increased fasting gastric volume (p = 0.01) and satiation (p < 0.01) at 16 weeks. GES T1/2 was positively correlated with weight loss on liraglutide (both p < 0.001). After 16 weeks of liraglutide, GLP1R rs6923761 (AG/AA vs. GG) was associated with reduced percent body fat (p = 0.062), and TCF7L2 rs7903146 (CC vs. CT/TT) was associated with lower body weight (p = 0.015).

Conclusions: Liraglutide, 3 mg, induces weight loss with delay in GES T1/2 and reduces calorie intake. Slowing GES and variations in GLP1R and TCF7L2 are associated with liraglutide effects in obesity.

Trial registration: ClinicalTrials.gov NCT02647944.

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Conflict of interest statement

Disclosures:

A. Acosta is a stockholder in Gila Therapeutics, Phenomix Sciences and Lipiquester; he serves as a consultant for Rhythm Pharmaceuticals, General Mills, Gila Therapeutics.

M. Camilleri is a stockholder in Phenomix Sciences (with current shares valued at less than U.S.$1.00) and serves as a consultant to Kallyope (with consulting fee paid to his employer, Mayo Clinic).

The other authors have no conflicts of interest.

Figures

Figure 1.
Figure 1.
Study design and gastric function testing in 136 participants over a 16-week period
Figure 2.
Figure 2.
CONSORT flow chart of participants; note discontinuation may have been recorded for more than one reason per withdrawal
Figure 3.
Figure 3.
Effects of liraglutide vs. placebo on gastric emptying T1/4 (upper left panel) and T1/2 (upper middle panel) at baseline, 5 weeks and 16 weeks of treatment showing group data (data show median, IQR); gastric emptying T1/2 in liraglutide group showing faster gastric emptying at 16 weeks compared to 5 weeks (upper right panel). Lower left panel shows relationship of change in gastric emptying T1/2 to change in weight at 5 and 16 weeks in both treatment groups. Lower right panel shows relationship of fastest quartile gastric emptying T1/2 at baseline to weight loss at 16 weeks in liraglutide group.
Figure 4.
Figure 4.
Effects of liraglutide vs. placebo on body weight at baseline, 5 weeks and 16 weeks of treatment (upper panel), and on kcal intake during nutrient drink test (VTF, volume to fullness and MTV, maximum tolerated volume) and ad libitum meal at baseline and 16 weeks (lower panel) showing group data (data show median, IQR).
Figure 5.
Figure 5.
Correlation of gastric emptying T1/2 at 5 weeks and 16 weeks and weight loss at 16 weeks in the liraglutide treatment group
Figure 6.
Figure 6.
Pharmacogenomics: effect of SNP variants in GLP1R and TCF7L2 on responses to liraglutide of phenotypes related to obesity
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