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. 2025 Mar;19(2):297-303.
doi: 10.1177/19322968241245680. Epub 2024 Apr 17.

Reduced Efficacy of Glucagon-Like Peptide-1 Receptor Agonists Therapy in People With Type 1 Diabetes and Genetic Forms of Obesity

Matthew P Klein  1 , Halis Kaan Akturk  1 , Janet K Snell-Bergeon  1 , Viral N Shah  2
Affiliations

Reduced Efficacy of Glucagon-Like Peptide-1 Receptor Agonists Therapy in People With Type 1 Diabetes and Genetic Forms of Obesity

Matthew P Klein et al. J Diabetes Sci Technol. 2025 Mar.

Erratum in

Abstract

Background: Once weekly Glucagon-Like Peptide-1 Receptor Agonists (GLP-1 RA) have been shown to improve glycemic outcomes and cause significant weight loss. However, 9% to 27% of individuals have little or no response to these drugs. In this article, we investigated the efficacy of GLP-1 RA therapy among adults with type 1 diabetes and obesity likely related to genetic mutations compared with obesity likely unrelated to genetic mutations.

Methods: In this retrospective study, we compared body weight and glycated hemoglobin (HbA1c) change with the use of GLP-1 RA therapy (including a dual agonist, Tirzepatide) over six months among adults with type 1 diabetes and obesity likely (n = 11, median age 39.5 years with a median BMI of 43.0 kg/m2) versus unlikely related to genetic mutation(s) (n = 15, median age 45.8 years with a median BMI of 38.7 kg/m2).

Results: Six months of GLP-1 RA treatment resulted in a numerically lower reduction of weight (-5.75 ± 9.46 kg vs -8.65 ± 9.36 kg, P = .44) and HbA1c (-0.28 ± 0.96% vs -0.43 ± 0.57%, P = .64) among individuals with obesity likely versus unlikely related to a genetic mutation(s), respectively. Fewer individuals with genetic obesity met goal weight loss ≥5% or HbA1c decrease ≥0.4% than did individuals with obesity unlikely related to a genetic cause (36.4% vs 80.0%, P = .04).

Conclusions: The weight loss and glycemic lowering effects of GLP-1 RA therapy may be decreased in people with type 1 diabetes and obesity likely related to genetic causes. Further research is needed to understand GLP-1 RA mechanisms via energy regulating genes.

Keywords: genetic mutations; genetics; glucagon-like peptide-1 receptor agonist (GLP-1 RA); obesity; type 1 diabetes mellitus.

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Conflict of interest statement

Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: HKA received research support through Medtronic, Tandem Diabetes, Mannkind, Eli Lilly, and Dexcom. He received honorarium for consulting from Medtronic, Tandem Diabetes, and Dexcom through the University of Colorado. VNS received research support from NovoNordisk, Insulet, Tandem Diabetes Care, and received honoraria from Dexcom, Embecta, Tandem Diabetes Care, Insulet, and NovoNordisk for speaking or consulting arrangements. MPK and JKS report no conflict of interest.

Figures

Figure 1.
Figure 1.
GLP-1 RA response frequency analysis.
See this image and copyright information in PMC

References

    1. Committee ADAPP. 9. Pharmacologic approaches to glycemic treatment: standards of care in diabetes—2024. Diabetes Care. 2024;47:S158-S178. doi:10.2337/dc24-S009. - DOI - PMC - PubMed
    1. Nauck MA, Quast DR, Wefers J, Meier JJ. GLP-1 receptor agonists in the treatment of type 2 diabetes–state-of-the-art. Mol Metab. 2021;46:101102. doi:10.1016/j.molmet.2020.101102. - DOI - PMC - PubMed
    1. Kristensen SL, Rørth R, Jhund PS, et al.. Cardiovascular, mortality, and kidney outcomes with GLP-1 receptor agonists in patients with type 2 diabetes: a systematic review and meta-analysis of cardiovascular outcome trials. Lancet Diabetes Endocrinol. 2019;7(10):776-785. - PubMed
    1. Fang M, Echouffo-Tcheugui JB, Selvin E. Prevalence and management of obesity in U.S. adults with type 1 diabetes. Ann Intern Med. 2023;176(3):427-429. doi: 10.7326/M22-3078. - DOI - PMC - PubMed
    1. Curtis L, Holt H, Richardson T, Knott J, Partridge H. GLP-1 analogue use in patients with sub-optimally controlled type 1 diabetes or obesity improves weight and HbA1c. Pract Diabetes. 2016;33(1):13-17.

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