Research Protocol: Effects of GLP-1 Therapy on Skeletal Muscle Health Across Stages of Type 2 Diabetes

Abstract

Introduction: Glucagon-like peptide-1 (GLP-1) agonists are key components of type-2 diabetes mellitus (T2DM) treatment due to their role in improving insulin secretion, inhibiting glucagon release, promoting lipid metabolism, and enhancing satiety. Recent studies have highlighted the possible drawback that comes with intended weight loss: muscle loss. This study seeks to better understand the significance of this muscle loss in terms of strength, function, and total mass lost in T2DM individuals with comorbid obesity.  

Methods: A 20-week treatment trial will investigate lean mass changes with the administration of GLP-1 agonists in 3 T2DM cohorts: insulin-reliant, metformin-reliant, and prediabetic groups, and their respective controls. Overall health analysis will occur through metrics such as total mass, lean mass, grip strength, 31P-MRS, quality of life questionnaires, HbA1c, and lipid panel. Through these, a holistic view on GLP-1 effectiveness, its relationship to unintended lean mass loss, and its health implications as a whole can be gained.  

Results: A relatively linear relationship between severity of T2DM and/or greater BMI and lean mass lost – both proportionally and absolutely – is anticipated. Similarly, the greater the severity of T2DM the more significant the decrease in muscle strength and function is predicted. Inversely, the most significant improvements in terms of HbA1c and lipid panel will be in the greater severity T2DM cohorts. Overall quality of life and patient experience will increase noticeably across all three treatment groups with respect to controls with slightly less increases with more severe T2DM.  

Discussion: This study improves GLP-1 usage guidelines through an investigation of the treatment over different populations. It exhibits the first literature utilizing 31P-MRS to gain insight on muscle function decreases across diabetic patients undergoing GLP-1 therapy. Possible co-treatments may be recommended in future studies to limit the lean mass lost in already susceptible populations. 

Conclusion: In conclusion, GLP-1 agonists demonstrate significant effects on lean mass, muscle strength, muscle function, and diabetic biomarkers, with the severity of T2DM varying the extent of the effects. While quality of life improvements are noticeable, the impact of GLP-1 treatment on muscle dynamics highlights complex interplay between muscle preservation and intended weight loss.