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09.05.2023 | Original Article

Glucagon-like peptide-1 analog therapy in rare genetic diseases: monogenic obesity, monogenic diabetes, and spinal muscular atrophy

verfasst von: Hussein Zaitoon, Ronit Lubetzky, Achiya Z. Amir, Hadar Moran-Lev, Liora Sagi, Michal Yacobi-Bach, Ophir Borger, Efrat Chorna, Yael Lebenthal, Avivit Brener

Erschienen in: Acta Diabetologica | Ausgabe 8/2023

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Abstract

Aim

Implementing genetic analyses have unraveled rare alterations causing early-onset obesity and complications, in whom treatment is challenging. We aimed to report on the effects of adjuvant off-label therapy with liraglutide, glucagon-like peptide-1 analogue (GLP-1a), in rare genetic diagnoses.

Methods

Case scenarios and review of the literature.

Results

Case 1: Nine-year-old boy with early-onset severe obesity and nonalcoholic fatty liver disease (NAFLD) due to a homozygous mutation in the MC4R gene deteriorated under lifestyle change and metformin therapy [at 10.5 years: body mass index (BMI) 51.2kg/m², 226% of the 95th percentile, fat percentage (FP) 65% and muscle-to-fat ratio (MFR) z-score of −2.41]. One year of liraglutide treatment halted progressive weight gain [BMI 50.3kg/m², 212% of the 95th percentile, 63.7% FP and MFR z-score of −2.34], with biochemical improvement.

Case 2: Twelve-year-old boy with obesity presented with diabetes and progressive NAFLD. Exome analysis revealed two heterozygous mutations compatible with monogenic diabetes (HNF1A) and familial hypercholesterolemia (LDLR). Lifestyle modifications resulted in clinical and laboratory improvement (BMI 87th percentile, 32.8% FP, MFR z-score of −1.63, HbA1c 5.5%) without the expected recovery in liver transaminases. Liraglutide treatment augmented the improvement in weight status (BMI 68th percentile, 22.6% FP, MFR z-score of −1.13) with normalization of liver transaminases.

Case 3: Nineteen-year-old male with spinal muscular atrophy type 3 presented with sarcopenic obesity and comorbidities. Treatment strategy included dietary counseling and multiple drug therapies (metformin, anti-hypertensive and statins). Liraglutide therapy led to a gradual recovery of metabolic complications allowing tapering-down other medications.

Conclusions

Considering the pleiotropic effects of GLP1-a beyond BMI reduction, this treatment modality may serve as a game changer in challenging cases.

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Titel: Glucagon-like peptide-1 analog therapy in rare genetic diseases: monogenic obesity, monogenic diabetes, and spinal muscular atrophy
verfasst von: Hussein Zaitoon
Ronit Lubetzky
Achiya Z. Amir
Hadar Moran-Lev
Liora Sagi
Michal Yacobi-Bach
Ophir Borger
Efrat Chorna
Yael Lebenthal
Avivit Brener
Publikationsdatum: 09.05.2023
Verlag: Springer Milan
Erschienen in: Acta Diabetologica / Ausgabe 8/2023
Print ISSN: 0940-5429
Elektronische ISSN: 1432-5233
DOI: https://doi.org/10.1007/s00592-023-02109-9

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Abstract

Aim

Methods

Results

Conclusions

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