Effect of Semaglutide on Aging Biomarkers in Older Adults

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T
he 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
 
Hinnen D Diabetes Spectrum 2017
 
FDA approved
-DM2
 
-Reduce CV disease in those
with DM2 or those with
established CV disease are
overweight
 
-Weight management
 
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
 
Behavioral Risk Factor Surveillance System, CDC
 
Overall, 41.5% of adults
60 and older are obese
 
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                                               Intervention 5months
Open label                          
   
Lifestyle alone
 
Screening (V1)
-Labs
-Questionnaires
-DXA
-Functional
assessments
 
V2, T=0
-Randomization
-Research Labs,
Muscle + Adipose
biopsy
-Lifestyle
counseling
 
V3, T+1 month
-Lifestyle
counseling
-Semaglutide
titration
 
V4, T+2 months
-Lifestyle
counseling
-
Semaglutide
titration
 
V5, T+3 months
-Lifestyle
counseling
-Semaglutide
maintenance
 
V6, T+5months
-Questionnaires
-DXA
-Functional
assessments
 
 
V7, T+5 months
-Research Labs
-Muscle and
Adipose Biopsy
 
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
 
Baseline Characteristics
 
Intervention Effects
 
Intervention Effects
 
Intervention Effects
 
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
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Questions?
 
CORTEST@UTHSCSA.EDU
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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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  1. 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

  2. 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

  3. 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

  4. 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

  5. Obesity in older adults Overall, 41.5% of adults 60 and older are obese Behavioral Risk Factor Surveillance System, CDC

  6. Weight loss in those with DM2 Davies et al JAMA 2015 Davies et al Lancet 2021

  7. 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

  8. Diabetes and Sarcopenia Veroense et al Eur Geriatr Med 2019

  9. A1c association with muscle mass Li S et al Front Nutr 2023

  10. 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

  11. 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

  12. 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

  13. 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

  14. 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

  15. 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

  16. 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

  17. 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

  18. 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

  19. 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

  20. 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

  21. 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

  22. 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

  23. Questions? CORTEST@UTHSCSA.EDU

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