Alterations in energy balance following exenatide administration.
Exenatide is a medication similar in structure and effect to native glucagon-like peptide-1, an incretin hormone with glucose-lowering properties. The aim of the study was to measure the change in total energy expenditure (TEE) and body composition during exenatide administration and by deduction the relative contributions of energy expenditure and energy intake to exenatide-induced weight loss. Forty-five obese (body mass index, 30-40 kg·m⁻²) subjects were identified. After exclusion criteria application, 28 subjects entered into the study and 18 subjects (12 female, 6 male) completed the study, which consisted of 6 visits over 14 weeks and injection of exenatide for an average of 84 ± 5 days. Respiratory gas analysis and doubly labeled water measurements were performed before initiation of exenatide and after approximately 3 months of exenatide administration. The average weight loss from the beginning of injection period to the end of the study in completed subjects was 2.0 ± 2.8 kg (p = 0.01). Fat mass declined by 1.3 ± 1.8 kg (p = 0.01) while the fat-free mass trended downward but was not significant (0.8 ± 2.2 kg, p = 0.14). There was no change in weight-adjusted TEE (p = 0.20), resting metabolic rate (p = 0.51), or physical activity energy expenditure (p = 0.38) and no change in the unadjusted thermic effect of a meal (p = 0.37). The significant weight loss because of exenatide administration was thus the result of decreasing energy intake. In obese nondiabetic subjects, exenatide administration did not increase TEE and by deduction the significant weight loss and loss of fat mass was due to decreased energy intake.
Department of Geriatrics and Nutritional Sciences, Washington University, St. Louis, MO 63102, USA. Dbradley@dom.wustl.edu
David P
DP
Bradley
Roger
R
Kulstad
Natalie
N
Racine
Yoram
Y
Shenker
Melissa
M
Meredith
Dale A
DA
Schoeller
D000273:Adipose Tissue / Q000187:drug effects / Q000473:pathology; D000328:Adult; D000465:Algorithms; D019440:Anti-Obesity Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001823:Body Composition / Q000187:drug effects; D015992:Body Mass Index; D002149:Energy Intake / Q000187:drug effects*; D004734:Energy Metabolism / Q000187:drug effects*; D000077270:Exenatide; D005260:Female; D052216:Glucagon-Like Peptide 1 / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D010352:Patient Dropouts; D010455:Peptides / Q000009:adverse effects / Q000627:therapeutic use*; D014688:Venoms / Q000009:adverse effects / Q000627:therapeutic use*; D015431:Weight Loss / Q000187:drug effects
D019440:Anti-Obesity Agents; D007004:Hypoglycemic Agents; D010455:Peptides; D014688:Venoms; D052216:Glucagon-Like Peptide 1; D000077270:Exenatide