Format

Send to

Choose Destination
J Clin Endocrinol Metab. 2015 Apr;100(4):1639-45. doi: 10.1210/jc.2014-4024. Epub 2015 Feb 12.

RM-493, a melanocortin-4 receptor (MC4R) agonist, increases resting energy expenditure in obese individuals.

Author information

1
Diabetes, Endocrinology, and Obesity Branch (K.Y.C., R.M., B.S.A., K.P.M., P.S., R.J.B., X.Z., M.R., T.L.P., M.L.R., M.C.S.), National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892; Department of Molecular Physiology and Biophysics (R.D.C., B.L.P.), Vanderbilt University School of Medicine, Nashville, Tennessee 37232; and Rhythm Pharmaceuticals (K.M.G., L.H.T.V.d.P.), Boston, Massachusetts 02116.

Abstract

CONTEXT:

Activation of the melanocortin-4 receptor (MC4R) with the synthetic agonist RM-493 decreases body weight and increases energy expenditure (EE) in nonhuman primates. The effects of MC4R agonists on EE in humans have not been examined to date.

OBJECTIVE, DESIGN, AND SETTING:

In a randomized, double-blind, placebo-controlled, crossover study, we examined the effects of the MC4R agonist RM-493 on resting energy expenditure (REE) in obese subjects in an inpatient setting.

STUDY PARTICIPANTS AND METHODS:

Twelve healthy adults (6 men and 6 women) with body mass index of 35.7 ± 2.9 kg/m(2) (mean ± SD) received RM-493 (1 mg/24 h) or placebo by continuous subcutaneous infusion over 72 hours, followed immediately by crossover to the alternate treatment. All subjects received a weight-maintenance diet (50% carbohydrate, 30% fat, and 20% protein) and performed 30 minutes of standardized exercise daily. Continuous EE was measured on the third treatment day in a room calorimeter, and REE in the fasting state was defined as the mean of 2 30-minute resting periods.

RESULTS:

RM-493 increased REE vs placebo by 6.4% (95% confidence interval, 0.68-13.02%), on average by 111 kcal/24 h (95% confidence interval, 15-207 kcal, P = .03). Total daily EE trended higher, whereas the thermic effect of a test meal and exercise EE did not differ significantly. The 23-hour nonexercise respiratory quotient was lower during RM-493 treatment (0.833 ± 0.021 vs 0.848 ± 0.022, P = .02). No adverse effect on heart rate or blood pressure was observed.

CONCLUSIONS:

Short-term administration of the MC4R agonist RM-493 increases REE and shifts substrate oxidation to fat in obese individuals.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT01867437.

PMID:
25675384
PMCID:
PMC4399297
DOI:
10.1210/jc.2014-4024
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Silverchair Information Systems Icon for PubMed Central
Loading ...
Support Center