MON-593 Single-Dose Effects of Anti-Obesity Drugs on Human Basal Metabolic Rate

• Published in: Journal of the Endocrine Society Vol. 4; no. Supplement_1
• Main Authors: Israni, Nikita Sanjay, Cassimatis, Thomas, Fletcher, Laura A, Leitner, Brooks P, Duckworth, Courtney J, Hattenbach, Jacob D, Bell, Sarah L, McGehee, Suzanne, Brychta, Robert J, Courville, Amber B, Bernstein, Shanna B, Muniyappa, Ranganath, Reitman, Marc L, Cypess, Aaron M, Chen, Kong Y
• Format: Journal Article
• Language: English
• Published: US Oxford University Press 08-05-2020
• Subjects: Adipose Tissue, Appetite, and Obesity
• DOI: 10.1210/jendso/bvaa046.366
• EISSN: 2472-1972

Design and rationale: Obesity results from energy intake exceeding energy expenditure (EE) over a prolonged period. Many anti-obesity drugs are designed to decrease energy intake. However, their potential impact on EE is not well documented. We designed a placebo-controlled, double-blind, randomized cross-over study to determine the acute effects of several FDA-approved anti-obesity drugs on basal metabolic rate (BMR) under well-controlled conditions.
Protocol and inclusion criteria: This ongoing study is limited to healthy males of all ethnicities aged 18–35 years with a BMI of 18.5 to 25.0 kg/m2. Following an overnight stay in the Metabolic Clinical Research Unit, fasting subjects were measured from 8:00am to 12:00pm in a whole-room indirect calorimeter, which was maintained at a thermoneutral temperature (26.7±0.9°C) to prevent non-shivering thermogenesis. The six treatments include placebo, caffeine as the positive control (300 mg), phentermine (37.5 mg), topiramate (200 mg), Qsymia (phentermine 15 mg / topiramate 92 mg), and naltrexone (100 mg), with a 1-week outpatient washout period after each treatment. Drug-naïve subjects received a single dose of each drug to minimize potential metabolic adaptations that may occur with weight-loss or chronic use. The prespecified primary outcome was a ≥5% increase in BMR vs. placebo for each drug. This difference can be detected for 16 subjects with 0.83 power at α=0.05 allowing for ≤25% dropout. Secondary outcomes include respiratory quotient (RQ), heart rate (HR), mean arterial pressure (MAP), and self-reported hunger.
Preliminary data: To date, 7 subjects were recruited and 6 have completed the study (26.1±4.3 years, BMI 23.1±1.4 kg/m2, body fat percentage 18.4±4.1%). Interim analysis using paired t-tests shows, compared to placebo, caffeine trended towards increasing EE (1.17±0.07 vs. 1.27±0.12 kcal/min; p=0.07) and increased MAP by 5.5±4.2% (88±2 vs. 93±4; p<0.05), but did not change heart rate (59±10 vs. 61±13 bpm). Naltrexone increased EE by 5.9±4.3% (p<0.05). No treatments altered resting RQ compared to placebo (0.83±0.05). Phentermine increased resting HR, both alone (15.7±7.9%, p<0.01) and in Qsymia (9.2±3.6%, p<0.05), compared to placebo. Of the five drug-treatments, only Qsymia reduced self-reported hunger scores compared to placebo.
Summary and future directions: Anti-obesity drugs may increase energy expenditure by upregulating sympathetic nervous system activity. Combined with appetite suppression, the impact on energy balance can lead to weight loss. We aim to complete our study to determine whether these drugs can acutely increase EE with minimal cardiovascular side-effects and compare our findings with long-term interventions.