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Clinical Trial
. 2021 Feb;23(2):363-373.
doi: 10.1111/dom.14224. Epub 2020 Oct 25.

A phase 3 randomized clinical trial using a once-weekly glucagon-like peptide-1 receptor agonist in adolescents and young adults with hypothalamic obesity

Christian L Roth  1   2 , Francisco A Perez  3 , Kathryn B Whitlock  1 , Clinton Elfers  1 , Jack A Yanovski  4 , Ashley H Shoemaker  5 , M Jennifer Abuzzahab  6
Affiliations
Clinical Trial

A phase 3 randomized clinical trial using a once-weekly glucagon-like peptide-1 receptor agonist in adolescents and young adults with hypothalamic obesity

Christian L Roth et al. Diabetes Obes Metab. 2021 Feb.

Abstract

Aim: To evaluate the efficacy, safety and tolerability of a glucagon-like peptide-1 receptor agonist (GLP-1 RA) in patients with hypothalamic obesity (HO).

Materials and methods: A two-arm, randomized, multicentre, double-blind, placebo-controlled trial was conducted in 10- to 25-year-olds with hypothalamic injury following intracranial tumour and HO. Participants were randomized to once-weekly subcutaneous injections of a GLP-1 RA exenatide 2 mg (ExQW) or placebo for 36 weeks. The primary efficacy endpoint was 36-week % change in body mass index (BMI). Secondary outcomes included change in body composition (by dual energy x-ray absorptiometry).

Results: Forty-two participants were randomized to ExQW (n = 23) or placebo (n = 19). Participants were 5 ± 2 years (mean ± SD) postdiagnosis and development of HO (BMI 37.3 ± 7.1 kg/m2 ). In intention-to-treat analysis, the effect of 36-week ExQW vs. placebo on % Δ BMI was not significant (estimated treatment difference -1.7 ± 1.8%, 95% CI -4.1 to 0.6%, P = .40); however, total body fat mass was reduced (estimated treatment difference -3.1 ± 1.4 kg, 95% CI -5.7 to -0.4 kg, P = .02). There was a significant reduction in waist circumference (estimated effect of treatment -3.5 [95% CI -5.5 to -1.6] cm, P = .004). All patients treated with placebo increased % of adipose tissue, while 50% treated with ExQW had reductions (P < .001). Mean HbA1c, glucose tolerance and serum lipids did not change significantly with therapy. ExQW was well tolerated. The most frequent adverse events were transient gastrointestinal disturbances (ExQW vs. placebo: nausea 6/23 vs. 3/18, vomiting 4/23 vs. 4/18 and diarrhoea 7/23 vs. 3/18).

Conclusions: GLP-1 RAs are a promising and safe treatment to improve or stabilize HO in children and young adults.

Keywords: antiobesity drug; exenatide; randomized trial.

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Conflict of interest statement

The authors declare no competing interests.

Figures

FIGURE 1
FIGURE 1
Consort diagram
FIGURE 2
FIGURE 2
Changes of weight‐related endpoints. Waterfall plots for A, exenatide once‐weekly (ExQW) and B, placebo treated patients outlining the % change in BMI from baseline to the end of the randomized treatment arm (36 weeks; grey bars) and the end of the open‐label arm (54 weeks; ◇, ExQW group only). Change in C and D, % body fat, and E and F, total body fat, during the randomized treatment. G, change in BMI over the first 18 weeks of ExQW during randomized versus open‐label treatment phases
See this image and copyright information in PMC

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