Predictors of weight‐loss response with glucagon‐like peptide‐1 receptor agonist treatment among adolescents with severe obesity
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Summary: In two previous, separate clinical trials, we demonstrated significant reductions in body mass index ( BMI ) with exenatide in adolescents with severe obesity. In the present study, we pooled data from these near identical trials to evaluate factors that may predict BMI reduction at 3 months. Data from 32 patients (mean age 14.3 ± 2.2 years; 69% female; mean BMI 39.8 ± 5.8 kg m −2 ) were included. Exenatide treatment consisted of 5 mcg twice daily for 1 month, followed by an increase to 10 mcg twice daily for 2 additional months. Predictor variables included baseline BMI , BMI percent change at 1 month, incidence of nausea or vomiting and baseline appetite and satiety measures. Treatment effects of percent change in BMI from baseline were estimated within predictor subgroups using generalized estimating equations with exchangeable working correlation and robust variance estimation for confidence intervals and P ‐values to account for paired observations. The pooled data treatment effect on absolute BMI at 3 months was −3.42% (95% confidence interval: −5.41%, −1.42%) compared to placebo. Within treated participants, appetite at baseline (treatment effect in high [−4.28%] vs. low [1.02%], P = 0.028) and sex (treatment effect in female [−4.78%] vs. male [0.76%], P = 0.007) were significant predictors of change in BMI at 3 months. Baseline BMI , BMI percent change at 1 month, age, incidence of nausea, vomiting, or other gastrointestinal symptoms and satiety scores did not predict 3‐month responses. Sex and measures of appetite may serve as useful predictors of glucagon‐like peptide‐1 receptor agonist treatment response among adolescents with severe obesity.
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Associations with acute pancreatitis and thyroid malignancy have been observed mainly in animal studies, and a cause-effect relationship among GLP-1 RAs and these outcomes has not been established in human clinical trials.
“Additionally, there have been a few associations with incidents of major adverse outcomes such as episodes of acute pancreatitis and thyroid malignancy. However, these have been observed mainly in animal studies and a cause–effect relationship among GLP-1 Ras, and these outcomes have not been established in human clinical trials [71].”
From Sex Differences in Response to Treatment with Glucagon-like Peptide 1 Receptor Agonists: Opportunities for a Tailored Approach to Diabetes and Obesity Care (2022) · cites this paper as [71]
The Methods section describes exenatide trials in adolescents and lists a history of pancreatitis as an exclusion criterion. The Results and Discussion address BMI response and gastrointestinal symptoms, but our copy does not discuss thyroid malignancy, animal-study findings about either outcome, or whether human trials have established a causal relationship. Searches for pancreatitis, thyroid malignancy, animal studies, and serious adverse outcomes found no passage supporting the attributed claim; page numbers were unavailable. (LLM, conf=0.76)
Experimental — accuracy not yet measuredSmaller studies have suggested several potential predictors of weight-loss response to GLP-1 receptor agonists, including baseline BMI, early BMI change, nausea and vomiting, delayed gastric emptying, appetite and satiety measures, and GLP-1 receptor polymorphisms, but the findings are inconclusive.
“The baseline BMI, BMI change at 1 month, incidence of nausea and vomiting, delayed gastric emptying shortly after intervention, baseline appetite and satiety measures and some polymorphisms in GLP-1 receptor were suggested as potential predictors by some smaller studies, but the results are inconclusive [7–9].”
From Efficacy of GLP-1 RA Approved for Weight Management in Patients With or Without Diabetes: A Narrative Review (2022) · cites this paper as [7]
No reliable models exist to predict an individual's weight-loss response to GLP-1 receptor agonists.
“The reliable models that might predict weight reducing potential at the individual level have not been identified yet.”
From Efficacy of GLP-1 RA Approved for Weight Management in Patients With or Without Diabetes: A Narrative Review (2022) · cites this paper as [7]
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Self-citation
- Authors
- Nathan, B. M., Rudser, K. D., Abuzzahab, M. J., Fox, C. K., Coombes, B. J., Bomberg, E. M., & Kelly, A. S.
- Affiliations
- University of Minnesota (US)
- Children's Minnesota (US)
- Corresponding author
- Nathan, B. M.
- Venue
- Clinical Obesity
- Publisher
- Wiley
- Published
- 2015-12-18
- Volume
- 6
- Issue
- 1
- Pages
- 73-78
- ISSN
- 1758-8103 (ISSN-L)
- 1758-8111
- PMC
- PMC4721217
- OpenAlex
- W2219239030
- Cited by
- 39
- References
- 27
- Citations by year
- 2026: 4 · 2025: 5 · 2024: 3 · 2023: 4 · 2022: 7 · 2021: 3 · 2020: 4 · 2019: 5 · 2018: 1 · 2017: 1 · 2016: 2
- FWCI
- 0.96
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Clinical Obesity (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Minnesota Obesity Center (P30DK050456 NORC)
- University of Minnesota Clinical and Translational Science Institute
- National Center for Advancing Translational Sciences (UL1TR000114)
- Topics
- Health Sciences › Medicine › Pharmacology › Pharmacology and Obesity Treatment
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Health Sciences › Medicine › Surgery › Bariatric Surgery and Outcomes
- Keywords
- GLP-1 receptor agonists, exenatide, adolescent obesity, morbid obesity, predictors of weight loss, body mass index, appetite, satiety, sex differences, nausea and vomiting, treatment response
- MeSH terms
- Glucagon-Like Peptide-1 Receptor, Exenatide, Glucagon-Like Peptide-1 Receptor Agonists, Adolescent, Child, Female, Humans, Hypoglycemic Agents, Male, Obesity, Morbid, Peptides, Venoms, Weight Loss, Body Mass Index, Treatment Outcome, Young Adult
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