Effect of Semaglutide on Aging Biomarkers in Older Adults
Semaglutide, a GLP-1 receptor agonist, shows promising effects on physical function, body composition, and aging biomarkers in older adults with diabetes. Studies suggest potential neuroprotective effects, improvement in skeletal muscle atrophy, and reduction in pro-inflammatory markers. Diabetes prevalence among older adults is high, with obesity being a prevalent issue. Addressing weight management and muscle health in aging populations can have significant benefits for overall health.
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The Effect of Semaglutide on Physical Function, Body Composition, and Biomarkers of Aging in Older Adults TIFFANY M CORTES, MD UT HEALTH SAN ANTONIO SAN ANTONIO GRECC
GLP1 receptor agonists FDA approved -DM2 -Reduce CV disease in those with DM2 or those with established CV disease are overweight -Weight management Hinnen D Diabetes Spectrum 2017
Other effects of GLP1 receptor agonists Possible neuroprotective effects in those with DM2 under than 65 In mice, there has been improvement of skeletal muscle atrophy Improvement of pro-inflammatory milieu with decreased levels of C reactive protein Tumor necrosis factor alpha Adiponectin Luan S et al Front Endocrinol 2022 Nguyen et al Front Pharmacol 2020 Hong et al Cachexia Sarcopenia Muscle 2019 Bray et al Diabetes Obes Metab 2021
DM2 in Older Adults 26.8% have diabetes 46.6% have prediabetes CDC Diabetes Statistics LeRoith D et al, J Clin Endocrinol Metab, 2019; 104
Obesity in older adults Overall, 41.5% of adults 60 and older are obese Behavioral Risk Factor Surveillance System, CDC
Weight loss in those with DM2 Davies et al JAMA 2015 Davies et al Lancet 2021
Aging Muscle Healthy adults lose -~8% of their muscle mass per decade between 40-70 years old ~15% per decade after 70 years old Marzetti et al Aging Clin Exp Res 2017 Cruz-Jentoft and Sayer Lancet 2019
Diabetes and Sarcopenia Veroense et al Eur Geriatr Med 2019
A1c association with muscle mass Li S et al Front Nutr 2023
Older Adult and Diabetes Clinical Trials Participation to Prevalence Ratio Blue lines indicate the PPR range of 0.8 to 1.2 often used to assess representativeness relative to the prevalent population Johnny Lau SW et al JAMA Netw Open 2022
AIMs To conduct a pilot study to examine the effect of GLP-1 receptor agonists on physical function and body composition in older overweight/obese adults with pre-DM or well controlled type 2 DM. To examine the impact of GLP-1 receptor agonists on biomarkers of aging in older overweight/obese adults with prediabetes or well controlled type 2 DM
Overview Conducted through Sam and Ann Barshop Institute for Longevity and Aging Studies 20-week single center, open label, randomized trial Lifestyle + semaglutide Lifestyle alone Goal to have 20 participants complete study from the community Overall a group of participants who could be prescribed this medication in clinic
Randomized, 1:1 Semaglutide + Lifestyle vs Open label Lifestyle alone Intervention 5months V5, T+3 months -Lifestyle counseling -Semaglutide maintenance Screening (V1) -Labs -Questionnaires -DXA -Functional assessments V3, T+1 month -Lifestyle counseling -Semaglutide titration V7, T+5 months -Research Labs -Muscle and Adipose Biopsy V2, T=0 V6, T+5months -Questionnaires -DXA -Functional assessments V4, T+2 months -Lifestyle counseling - Semaglutide titration -Randomization -Research Labs, Muscle + Adipose biopsy -Lifestyle counseling
Project Status Screenings started April 2023 All visit 6 completed as of 4/23/2024!! Two more visit 7 pending Friday and Tuesday, fingers crossed
Baseline Characteristics Lifestyle Semaglutide + Lifestyle P-value Age, yrs 73.4 (4.9) 71.9 (4.9) 0.50 Gender M/F 10/10 10/10 Hispanic 4 5 0.65 Glucose 104.6 (14.9) 103.8 (24.5) 0.93 Hemoglobin A1c 6.0 (0.4) 6.0 (0.4) 0.87
Baseline Characteristics Lifestyle Semaglutide + Lifestyle P-value Weight, kg 95.7 (15.9) 90.0 (18.1) 0.47 BMI, kg/m2 34.0 (3.7) 32.2 (4.2) 0.31 Adipose, kg 37.7 (5.9) 33.1 (8.6) 0.18 Lean Mass, kg 54.0 (11.5) 50.5 (12.1) 0.51 Grip strength, kg 30.4 (8.4) 28.5 (7.1) 0.60 6 min walk, ft 1264.7 (216.5) 1101.6 (320.8) 0.20 SPPB 9.8 (2.5) 8.5 (3.7) 0.37
Intervention Effects Lifestyle Semaglutide + Lifestyle P-value Glucose -7.0 (38.8) -12.4 (19.4) 0.69 Hemoglobin A1c 0.1 (0.3) -0.5 (0.4) <0.01 BMI -0.3 -1.8 <0.01 Weight -0.7 (2.1) -5.0 (3.2) <0.01
Intervention Effects Lifestyle Semaglutide + Lifestyle P-value Weight -0.7 (2.1) -5.0 (3.2) <0.01 Adipose .1 (2.5) -2.7 (1.9) 0.01 Lean Mass -1.2 (3.0) -2.0 (2.0) 0.47
Intervention Effects Lifestyle Semaglutide + Lifestyle P-value Grip strength -2.2 (3.5) -2.0 (3.2) 0.85 6 min walk, ft -20.7 (119) 10.9 (161) 0.62 SPPB 0.3 (0.9) 0.6 (1.4) 0.63
Analysis of Blood, Muscle, Adipose Serum Immunoassays Growth differentiation factor 15, tumor necrosis factor receptor II, chemokine ligands 3/4, FAS, TNFalpha, C-reactive protein Muscle PCR measurement IL-6, p16, p21, Toll like receptor 4, Monocyte chemoattractant protein 1 Beta galactosidase staining adipose
Summary Semaglutide caused a significant weight loss in older adults without a significant change in lean mass compared to lifestyle modifications alone Semaglutide did not cause a significant change in physical function compared to lifestyle modifications alone Analysis on biomarkers of aging will start soon
Thank you! Sara Espinoza, MD, MSc Nick Musi, MD Monica Serra, PhD Barshop Clinical and Administrative Staff Support from NIA Diversity Supplement R01AG052697-04S1 San Antonio Older Adults Independence Center San Antonio GRECC
Questions? CORTEST@UTHSCSA.EDU
