GLP-1 Analog Modulates Appetite, Taste Preference, Gut Hormones, and Regional Body Fat Stores in Adults with Obesity

Abstract

Purpose: Obesity is associated with alterations in appetite, gastrointestinal hormone levels and excessive fat mass. We previously published a double-blind, placebo-controlled, randomized, 16-week trial on effects of once-daily glucagon-like peptide-1 (GLP-1) analog, liraglutide on weight, satiation, and gastric functions in obese volunteers. The aim of this substudy is to compare to placebo the effects of liraglutide on appetite, taste preference, regional body fat stores, and anthropometric measurements.

Methods: Forty obese adults received standard instruction for weight management, monthly behavioral intervention utilizing motivational interviews, and 16-week treatment of once-daily liraglutide (escalated to 3 mg SQ daily). At baseline and 16 weeks, the following were measured: appetite and taste preferences rated every 30 min for 5 h after ingesting 300 mL Ensure®; maximal tolerated volume (MTV) with a nutrient drink test; fasting and postprandial bioactive GLP-1 (7-36) and peptide YY (PYY) levels; total and regional body fat with dual-energy X-ray absorptiometry, and waist and hip circumference.

Results: Thirty-five participants (17 liraglutide; 18 placebo) completed the trial. Compared to placebo group, liraglutide group had significant reductions in MTV; prospective food consumption score; desire to eat something sweet, salty, savory or fatty; and an increase in perceived fullness. Postprandial plasma levels of GLP-1 decreased and PYY levels increased with liraglutide relative to baseline. Significant reductions in total body, trunk, and upper and lower body fat without reduction in lean body mass were observed.

Conclusion: Liraglutide 3 mg SQ modulates appetite, taste preference, gut hormones, and regional body fat stores in adults with obesity without reduction in lean body mass.

Trial registration: ClinicalTrials.gov NCT02647944.

Keywords: GLP-1 analog; appetite; body fat; liraglutide; obesity; taste preference.

© Endocrine Society 2019. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Figures

Figure 1.

Study protocol.

Figure 2.

Appetite and taste preference Visual Analog Scale form.

Figure 3.

Sample DXA body composition scan generated by enCORE software. This image represents the baseline full body DXA scan obtained for a 22-year-old female participant with a BMI of 33.6 kg/m2. Standard regions of interest (ROI) that were assessed by DXA: upper body (android) and trunk regions (associated with risk of chronic disease); lower body (gynoid) region. ROI boundaries in this image were highlighted by study staff.

Figure 4.

CONSORT flow chart.

Figure 5.

Appetite ratings at 16 weeks in the two groups (assessed by visual analog scale, Fig. 2) following the ingestion of a standard liquid breakfast. For each timepoint (0–300 min), average score (± standard error of the mean) of all participants per group was obtained for this figure. AUC0-300 min for each parameter and statistical analysis results can be found in Table 1. Abbreviations: OAS, overall appetite score = [satiety + fullness + (100 – hunger) + (100 – prospective food consumption)]/4.

Figure 6.

Effect of liraglutide on taste preference compared to placebo. The box plots represent median taste scores for each group. For each individual participant, average score of all timepoints (0–300 min) was obtained for this figure. A higher value on the VAS indicates lower preference for the specified taste (Fig. 2). P-values reflect Wilcoxon’s Rank Sum analysis of the area under the curve. Abbreviation: ETD, estimated treatment difference.

Figure 7.

Plasma levels of GI hormones at 16 weeks in the 2 groups. GLP-1 and PYY levels were assessed during fasting (0 min), and at 15, 45, and 90 min postprandially. For each timepoint (0–90 min), average score (± standard error of the mean) of all participants per group was obtained for this figure. AUC0-90 min for each hormone and statistical analysis results can be found in Table 2.

Figure 8.

Box-plot graphs showing the significant decrease in percentage total body and upper body, lower body, and trunk fat with liraglutide compared to placebo. P-values reflect analysis of covariance analysis with baseline %fat as covariate. $Wilcoxon rank sum test.

Figure 9.

Box-plot graphs showing the significant decrease in total weight, but not in lean body mass, with liraglutide compared to placebo. P-values reflect analysis of covariance analysis with baseline measure as covariate.