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

Apr 17, 2024Journal of diabetes science and technology

Lower effectiveness of GLP-1 receptor agonist treatment in people with type 1 diabetes and inherited obesity

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Abstract

Six months of GLP-1 RA therapy resulted in a numerically lower reduction of weight and HbA1c in individuals with obesity likely related to genetic mutations.

Individuals with obesity likely related to genetic mutations experienced a weight reduction of -5.75 kg compared to -8.65 kg for those unlikely related to genetic causes.
The change in HbA1c was -0.28% for those with genetic obesity versus -0.43% for those without.
Only 36.4% of individuals with genetic obesity met the target weight loss of ≥5% compared to 80.0% of those without genetic causes.
The findings suggest that GLP-1 RA therapy may be less effective for individuals with type 1 diabetes and obesity likely related to genetic causes.

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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/m) versus unlikely related to genetic mutation(s) (n = 15, median age 45.8 years with a median BMI of 38.7 kg/m). 2 2

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,= .44) and HbA1c (-0.28 ± 0.96% vs -0.43 ± 0.57%,= .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%,= .04). P P P

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.

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

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