Exenatide has a pronounced effect on energy intake but not energy expenditure in non-diabetic subjects with obesity: A randomized, double-blind, placebo-controlled trial.

AIMS: Exenatide is a glucagon-like peptide 1 (GLP-1) mimetic which induces weight loss predominantly, it is presumed, via decreased food intake. However, circulating GLP-1 is also a determinant of energy expenditure. We sought to quantify the effect of exenatide on energy expenditure (EE) and energy intake. MATERIALS AND METHODS: In this single-center, randomized double-blind placebo controlled trial, we randomized 80 healthy, non-diabetic volunteers with obesity (46 women, age: 34.4 ±â€¯8.7 y, body fat by DXA: 44.2 ±â€¯7.8%) to subcutaneous exenatide 10 µg twice daily or placebo. Subjects were admitted to our clinical research unit for measurement of 24 h-EE in a whole-room indirect calorimeter and ad libitum food intake using an automated vending machine paradigm before and after randomization. Furthermore, energy expenditure and ad libitum food intake measures were repeated at 24-week after readmission for 7-day inpatient stay. Body weight was obtained weekly for up to 5 weeks and was recorded at each monthly follow up visit up to 24 weeks. RESULTS: Prior to randomization, participants over ate during the 3-day vending machine period in the whole study group (114.6 ±â€¯35.2%), expressed as percentage of weight maintaining energy needs (WMEN) with those who were eventually randomized to exenatide overeating more (121.6 ±â€¯37.7%) compared to placebo group (107.6 ±â€¯31.5%). In the exenatide group, ad libitum absolute energy intake decreased by 1016.1 ±â€¯724.5 kcal/day (95% CI: -1250.9 to -781.2) versus a 245.1 ±â€¯710.5 kcal/day (95% CI: -475.4 to -14.7) decrease in placebo (Δ = -624.8 Kcal/day, p < 0.0001) whereas the reduction in ad libitum caloric intake relative to WMEN was a more modest 366.8 ±â€¯752.1 kcal/day (95% CI: -614.0 to -119.6) decrease compared to 8.0 ±â€¯860.1 kcal/day (95% CI: -286.8 to 270.8) reduction in placebo (Δ = -382.3 Kcal/day, p = 0.03). The decrease was uniform across all macronutrients groups. No differences in 24hEE or substrate oxidation rates were found. In the exenatide group, body weight decreased more over the 5 weeks (ß = -0.039 kg/week, p = 0.02) and was lower compared to placebo at the end of fifth week (-1.48 ±â€¯0.77 kg; 95% CI: -3.02 to 0.05, p = 0.06). At the 24-week follow up, there was no difference in energy intake between exenatide group and placebo group and the treatment group decreased 24-h EE more compared to placebo (ß = -160.6 Kcal/day, 95% CI: -307.6 to 13.6, p = 0.03) compared to their pre-randomization measurement. However, this reduction was not present after adjustment for changes in FM and FFM (ß = -87 kcal/day, p = 0.14). No difference was observed in body weight (Δ = -1.72 kg, 95% CI: -5.77 to 2.30, p = 0.39) in exenatide versus placebo over 24 weeks. CONCLUSION: Compared with placebo, exenatide decreased early ad libitum energy intake but did not change 24 h-EE. However, the reduction was more modest in relative versus absolute terms (i.e. below that needed for WMEN). Thus, although rate of weight change was greater in the exenatide treated subjects at 5 weeks, the absolute difference in weight was not significant. These findings indicate that although exenatide reduces food intake, it may be more beneficial in blunting overeating and thus may serve to more prevent weight regain following initial weight loss.

Soda consumption during ad libitum food intake predicts weight change.

Soda consumption may contribute to weight gain over time. Objective data were used to determine whether soda consumption predicts weight gain or changes in glucose regulation over time. Subjects without diabetes (128 men, 75 women; mean age 34.3±8.9 years; mean body mass index 32.5±7.4; mean percentage body fat 31.6%±8.6%) self-selected their food from an ad libitum vending machine system for 3 days. Mean daily energy intake was calculated from food weight. Energy consumed from soda was recorded as were food choices that were low in fat (<20% of calories from fat) or high in simple sugars (>30%). Food choices were expressed as percentage of daily energy intake. A subset of 85 subjects had measurement of follow-up weights and oral glucose tolerance (57 men, 28 women; mean follow-up time=2.5±2.1 years, range 6 months to 9.9 years). Energy consumed from soda was negatively related to age (r=-0.27, P=0.0001) and choosing low-fat foods (r=-0.35, P<0.0001), but positively associated with choosing solid foods high in simple sugars (r=0.45, P<0.0001) and overall average daily energy intake (r=0.46, P<0.0001). Energy intake from food alone did not differ between individuals who did and did not consume beverage calories (P=0.11). Total daily energy intake had no relationship with change in weight (P=0.29) or change in glucose regulation (P=0.38) over time. However, energy consumed from soda correlated with change in weight (r=0.21, P=0.04). This relationship was unchanged after adjusting for follow-up time and initial weight. Soda consumption is a marker for excess energy consumption and is associated with weight gain.