Eliminating childhood obesity, one injection at a time: use of exenatide in adolescents shows promise for weight loss.
There is an alarming growth rate of children who are suffering from obesity; the data states that there are 40 million children under the age of 5 years old worldwide who suffer from obesity. A common treatment strategy is lifestyle modification, which has a low success rate. Pharmacological treatment is another option that could be used to combat pediatric obesity. Glucagon-like peptide-1 receptor agonists (GLP-1 RA), although initially used for the treatment of type 2 diabetes, are known to reduce weight in adults who suffer from obesity. There is limited data on the efficacy, safety, and tolerability of extended‐release GLP‐1 analog in the pediatric age group, neither for type 2 diabetes nor obesity. The RCT Combat-JUDO (Combating JUvelile Diabetes and Obesity) study was conducted to explore the effects of adolescents with obesity receiving exenatide extended-release once weekly on their BMI, glucose metabolism, liver steatosis, and associated cardiometabolic risk parameters, as well as safety and tolerability.
The RCT Combat-JUDO was a 6‐month parallel, double‐blinded, randomized, placebo-controlled two‐arm study with 44 participants aged 10-18 years old with obesity. Lifestyle intervention, plus either exenatide 2 mg or placebo subcutaneous injections once weekly, were given to the subjects. Of the patients selected, 22 were to receive exenatide, and 22 were to receive a placebo, which required that 52 patients were screened. The study was conducted from September 2015 to September 2016. It contained seven visits at the study site and six telephone contacts in between visits, and a follow‐up visit two weeks after the last dose of study medication. Males or females age 10 to 18 years and five months with obesity, sexually inactive or usage of adequate anticonception, negative pregnancy tests in females, and the ability to understand and comply with the requirements of the study were included in this study. Lifestyle intervention was implemented to all participants, which consisted of 4 nutritional sessions, four psychological sessions, and physical treatment.
Researchers found that the BMI‐SDS was significantly decreased in the exenatide compared with the placebo group over the 24‐week study period. After 24 weeks, exenatide reduced BMI‐SDS by 0.09 (−0.18, 0.00; P < .05), corresponding to 3.0 kg (−5.8, −0.1; P < .05) weight reduction, BMI by 0.83 kg/m2 (−1.68, 0.01; P < .05) and BMI as % of the 95th percentile by 2.9% (−5.4, −0.3; P < .05). Also, exenatide reduced waist circumference by 3.2 cm (−5.8, 0.7; P < .05) and SAT by 552 cm3 (−989. −114; P < .05). VAT was not reduced significantly. It was also discovered that there were reductions in subcutaneous adipose tissue, 2-hour glucose during the oral glucose tolerance test, and total cholesterol without changes in liver fat content.
Safety of the injectable GLP-1 receptor agonist in the adolescent subjects was studied as well. The number of adverse events was similar between the two groups. The most common adverse events were gastrointestinal (flatulence, nausea, diarrhea, constipation, abdominal pain, burping, vomiting, and mouth pain) (18 exenatide vs. ten placebo), infections (respiratory, gastrointestinal, and urinary) (18 exenatide vs. 20 placebo), and nervous system disorders (headache, dizziness, syncope, tremor of hands, and paresthesia) (16 exenatide vs 13 placebo). No serious adverse events occurred that were deemed related to the study drug.
Adherence to the study medication was good to excellent; this could partially be because less frequent dosing might be more attractive to adolescents.
Improved glycemic control with decreased 2‐hour glucose value during oral glucose tolerance test and reduced total and LDL cholesterol were recorded in subjects taking the GLP‐1 analog. The reducing effect of the GLP‐1 analog may be of considerable importance given the increased risk of adolescents with obesity to develop cardiovascular disease, glucose intolerance, and type 2 diabetes. Researchers stated that “Given the burden of childhood obesity and the risk of developing complications including type 2 diabetes, the present study gives support for GLP-1 receptor agonists as attractive treatment alternatives for this patient group, where pharmacological alternatives are minimal.” They added, “Future trials testing other GLP-1 receptor agonists in adolescents, which have shown clinically promising effects on reduction in BMI-SDS and other associated BMI metrics and measures of comorbidities, are warranted.”
The Combat‐JUDO study is a pioneer study that provides the first evidence that extended‐release exenatide treatment is feasible, generally well tolerated, and leads to reduction, albeit modest, in BMI‐SDS in adolescents with obesity.
- Extended–release exenatide is effective in weight reduction in adolescents, with the promise of possibly reducing childhood obesity.
- In comparison to exenatide twice daily, exenatide once weekly has a similar pharmacodynamic profile except for fewer side effects and better dyslipidemia reduction in the once–weekly formulation.
- High adherence, absence of severe adverse events, and reduction of other measures of comorbidities show a promise that this could eventually be a new treatment for those who suffer from childhood obesity.
Weghuber, D., et al. “A 6‐Month Randomized, Double‐Blind, Placebo‐Controlled Trial of Weekly Exenatide in Adolescents with Obesity.” Wiley Online Library, John Wiley & Sons, Ltd, 16 Feb. 2020, onlinelibrary.wiley.com/doi/full/10.1111/ijpo.12624.
Chardae Whitner, 2020 PharmD. Candidate, Lake Erie College of Osteopathic Medicine