GLP-1 Receptor Agonist Initiation Is Associated With Excess Skeletal Muscle Loss in Adults With Diabetes: A Prospective Population-Based MRI Study
- 1TUM - Klinikum rechts der Isar
Abstract
ObjectiveTo determine whether glucagon-like peptide 1 receptor agonist (GLP-1 RA) initiation is associated with excess skeletal muscle loss on repeat whole-body MRI.
Research Design and MethodsIn the German National Cohort, 58 adults with diabetes who initiated a GLP-1 RA between whole-body MRI examinations 4.6 years apart were matched on sex, age, BMI, and interval to 130 never-exposed controls with diabetes. Deep-learning-segmented tissue volumes were compared within matched sets.
ResultsSkeletal muscle volume declined 2.75 percentage points more in initiators (95% CI -4.51 to -0.99; P = 0.003), with 2.54 percentage points greater weight loss (P = 0.021). Adipose tissue differences (-4.8% internal torso, -3.2% subcutaneous) were nonsignificant.
ConclusionsIn this first population-based comparison of whole-body MRI before and after GLP-1 RA initiation with matched unexposed controls, initiators lost roughly 60% more muscle. Skeletal muscle loss is a measurable component of GLP-1 RA weight loss in routine care.
Article HighlightsO_LIWhy did we undertake this study? Rapid uptake of GLP-1 RAs has outpaced evidence on long-term muscle change during routine treatment. C_LIO_LIWhat is the specific question we wanted to answer? We asked whether GLP-1 RA initiation was associated with excess muscle and fat loss versus matched controls with diabetes. C_LIO_LIWhat did we find? Over 4.6 years, initiators lost roughly 60% more skeletal muscle than matched controls (-2.75 percentage points) alongside greater weight loss. Each additional kilogram lost was accompanied by about 100 mL of additional muscle loss. C_LIO_LIWhat are the implications of our findings? Skeletal muscle loss is a measurable component of GLP-1 RA-associated weight loss in routine care. Muscle mass should be monitored during treatment, and muscle-preservation strategies such as resistance training and adequate protein intake need evaluation. C_LI
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BibTeX
@misc{stambollxhiu2026glp1,
title = {{GLP-1 Receptor Agonist Initiation Is Associated With Excess Skeletal Muscle Loss in Adults With Diabetes: A Prospective Population-Based MRI Study}},
author = {E. Stambollxhiu and J. Luebberstedt and M. Kumpf and S. N. Willich and T. Keil and T. Pischon and T. Niendorf and A. Peters and S. Ziegelmayer and M. R. Makowski and K. K. Bressem and L. C. Adams},
howpublished = {medRxiv},
year = {2026},
month = sep,
doi = {10.64898/2026.09.15.26363157},
url = {https://www.medrxiv.org/content/10.64898/2026.09.15.26363157v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - GLP-1 Receptor Agonist Initiation Is Associated With Excess Skeletal Muscle Loss in Adults With Diabetes: A Prospective Population-Based MRI Study
AU - E. Stambollxhiu
AU - J. Luebberstedt
AU - M. Kumpf
AU - S. N. Willich
AU - T. Keil
AU - T. Pischon
AU - T. Niendorf
AU - A. Peters
AU - S. Ziegelmayer
AU - M. R. Makowski
AU - K. K. Bressem
AU - L. C. Adams
PY - 2026
DA - 2026/09/15
PB - medRxiv
DO - 10.64898/2026.09.15.26363157
UR - https://www.medrxiv.org/content/10.64898/2026.09.15.26363157v1
AB - ObjectiveTo determine whether glucagon-like peptide 1 receptor agonist (GLP-1 RA) initiation is associated with excess skeletal muscle loss on repeat whole-body MRI. Research Design and MethodsIn the German National Cohort, 58 adults with diabetes who initiated a GLP-1 RA between whole-body MRI examinations 4.6 years apart were matched on sex, age, BMI, and interval to 130 never-exposed controls with diabetes. Deep-learning-segmented tissue volumes were compared within matched sets. ResultsSkeletal muscle volume declined 2.75 percentage points more in initiators (95% CI -4.51 to -0.99; P = 0.003), with 2.54 percentage points greater weight loss (P = 0.021). Adipose tissue differences (-4.8% internal torso, -3.2% subcutaneous) were nonsignificant. ConclusionsIn this first population-based comparison of whole-body MRI before and after GLP-1 RA initiation with matched unexposed controls, initiators lost roughly 60% more muscle. Skeletal muscle loss is a measurable component of GLP-1 RA weight loss in routine care. Article HighlightsO_LIWhy did we undertake this study? Rapid uptake of GLP-1 RAs has outpaced evidence on long-term muscle change during routine treatment. C_LIO_LIWhat is the specific question we wanted to answer? We asked whether GLP-1 RA initiation was associated with excess muscle and fat loss versus matched controls with diabetes. C_LIO_LIWhat did we find? Over 4.6 years, initiators lost roughly 60% more skeletal muscle than matched controls (-2.75 percentage points) alongside greater weight loss. Each additional kilogram lost was accompanied by about 100 mL of additional muscle loss. C_LIO_LIWhat are the implications of our findings? Skeletal muscle loss is a measurable component of GLP-1 RA-associated weight loss in routine care. Muscle mass should be monitored during treatment, and muscle-preservation strategies such as resistance training and adequate protein intake need evaluation. C_LI
ER -