Clinical trial NCT05786521
Conditions: Aging Diabetes Mellitus, Type 2 PreDiabetes Overweight and Obesity
Sponsor: The University of Texas Health Science Center at San Antonio
Start date: 2023-04-01; Completion date: 2024-05-20
Enrollment: 20 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
Semaglutide is a medication approved by the US Food and Drug Administration (FDA) as an antihyperglycemic (a drug that reduces glucoses in those with diabetes) and for weight management. This new study will help find out what effects, semaglutide has on people who take the drug and the drug's effect on physical function, body composition, and aging.

Detailed description:

Arms: arm 1: Participants will meet with a dietician throughout the study to discuss lifestyle counseling based on recommendation in the diabetes prevention program. They will also be given semaglutide for 20 weeks. arm 2: Participants will meet with a dietician throughout the study to discuss lifestyle counseling based on recommendation in the diabetes prevention program
Interventions: intervention 1: Semaglutide Injectable Product intervention 2: Lifestyle Counseling
Intervention descriptions: intervention 1: Semaglutide will be started at 0.25mg once a week for 4 weeks followed by 0.5mg once weekly for 4 weeks followed by 1.0mg once a week for 12 weeks. intervention 2: Lifestyle Counseling will be provided throughout study intervention

Protocol documents:
ICF_000.pdf: 
Title of Study: The Effect of GLP1 Receptor Agonists on Physical Function, Body Composition, and Biomarkers of Aging 
in Older Overweight/Obese Adults with Insulin Resistance 
 
22-256H, Cortes, Form D, 08-30-23, AMD.docx 
 
Page 1 of 19 
UT Health San Antonio Research Consent and Authorization Documents (v June 29 2021) 
 
COVER PAGE  
 
 
 
 
 
Official Study Title: The Effect of GLP1 Receptor Agonists on Physical Function, 
Body Composition, and Biomarkers of Aging in Older Overweight/Obese Adults 
with Insulin Resistance 
 
NCT number: NCT05786521 
 
IRB Approval Date: 08.30.2023 
 
 
Unique Protocol ID: 20220256HU 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


Title of Study: The Effect of GLP1 Receptor Agonists on Physical Function, Body Composition, and Biomarkers of Aging 
in Older Overweight/Obese Adults with Insulin Resistance 
 
22-256H, Cortes, Form D, 08-30-23, AMD.docx 
 
Page 2 of 19 
UT Health San Antonio Research Consent and Authorization Documents (v June 29 2021) 
 
 
 
Concise Summary 
 
Important Information  
This information gives you an overview of the research.  More information about these topics may be found in the 
pages that follow.  You may choose not to take part in the study or may choose to leave the study at any time.  
Deciding not to participate, or deciding to leave the study later, will not result in any penalty or loss of benefits to 
which you are entitled and will not affect your relationship with us. 
 
1. What problem is this study trying to solve? 
You are being asked to participate in a research study.  Scientists do research to answer important questions which 
might help change or improve the way we do things in the future. Insulin resistance (prediabetes or diabetes) is 
associated with sarcopenia (decrease muscle mass), functional decline, and an increase in known markers of 
biological aging. These factors are not usually considered in choosing medications for the treatment of diabetes. 
The purpose of this research is to evaluate whether older adults with prediabetes or diabetes can benefit from taking 
a diabetes drug called semaglutide (brand name Ozempic) in addition to lifestyle counseling to improve physical 
function, body composition, and biological markers of aging compared to lifestyle counseling alone.  
 
For more information, please see the Why is this Study being Done section below.   
 
2. What will happen to me during the study and how is this different from continuing with usual care? 
What are all my options for treatment, including the pros and cons? 
Eligible participants will undergo medical history, physical examination, and screening blood tests. They will receive 
random assignments to either receive study medication and education on lifestyle modification or education on 
lifestyle modification alone over the course of about 6 months. Participants will complete pre- and post-treatment 
testing including evaluations of physical function by measures like grip strength, walking speed and distance, 
evaluation of body composition by a body composition scan (called a DXA scan), measurement of body mass index 
(BMI), surveys, and adipose (fat) and muscle samplings.  
 
For more information, please see the What will be done if you decide to be in the research section below.   
 
3. How much time will I spend on the study? 
The study involves a total of 8 visits over the course of approximately 20 weeks. Visits will occur at the start of the 
study, 3 weeks into the study, 7 weeks into the study, 11 weeks into the study and at the end of the study. During 
the study, you may have televisits (phone or virtual visits) for lifestyle modification education or checking on your 
progress. The longest in-person visits will be the second and the sixth visit due to assessments and procedures 
needing completion, approximately 4 hours. The other in-person visits should each last approximately 2 hours.  
 
4. Could taking part in the study help me and are there risks?  
We cannot guarantee that you will benefit from participating in this study, but you may benefit from learning more 
about lifestyle changes and receiving study-related clinical care that is at no cost to you. There is a small amount of 
reimbursement for your time and travel to the research unit. 
 
The risks associated with your participation may include side effects of the study medication, pain or bleeding from 
the blood draws or adipose and muscle biopsies, emotional distress from assessments, or fatigue from physical 
performance measures. The DXA scan does have a small amount of radiation.  
 
For more information, please see How could you or others benefit from your taking part in this and What are 
the risks of participation in the research sections below. 
 
5. What else should I consider before I make my decision? 
This study will involve attending study visits at the Barshop Institute Clinical Research Unit (BICRU) 4939 Charles 
Katz Dr.  
 


Title of Study: The Effect of GLP1 Receptor Agonists on Physical Function, Body Composition, and Biomarkers of Aging 
in Older Overweight/Obese Adults with Insulin Resistance 
 
22-256H, Cortes, Form D, 08-30-23, AMD.docx 
 
Page 3 of 19 
UT Health San Antonio Research Consent and Authorization Documents (v June 29 2021) 
 
Please review the rest of this document for additional details about these topics and other information you 
should know before making a decision about participating in this research. 
 


Title of Study: The Effect of GLP1 Receptor Agonists on Physical Function, Body Composition, and Biomarkers of Aging 
in Older Overweight/Obese Adults with Insulin Resistance 
 
22-256H, Cortes, Form D, 08-30-23, AMD.docx 
 
Page 4 of 19 
UT Health San Antonio Research Consent and Authorization Documents (v June 29 2021) 
 
Consent to be part of a Research Study 
To be conducted at  
University of Texas Health Science Center at San Antonio (UT Health San Antonio) 
 
Information about this form 
You may be eligible to take part in a research study. This form gives you important information about the study.   
 
Please take time to review this information carefully.  You should talk to the researchers about the study and 
ask them any questions you have.  You may also wish to talk to others (for example, your friends, family, or a 
doctor) about your participation in this study.  If you decide to take part in the study, you will be asked to sign 
this form.  Before you sign this form, be sure you understand what the study is about, including the risks and 
possible benefits to you. 
 
Please tell the researchers or study staff if you are taking part in another research study. 
 
Voluntary Participation - You do not have to participate if you don't want to.  You may also leave the study at 
any time.  If you leave the study before it is finished, there will be no penalty to you, and you will not lose any 
benefits to which you are entitled.   
 
General Information – “Who is conducting this research?” 
Principal Investigator 
The Principal Investigator (PI) is the researcher directing this study; the PI is responsible for protecting your 
rights, safety, and welfare as a participant in the research.  The PI for this study is Tiffany Cortes, MD, 
Assistant Professor, UTHSA Department of Medicine, Endocrinology Division. 
 
Funding  
The National Institute of Aging (NIH-NIA) Claude D. Pepper Older Americans Independence Center, a federal 
agency that promotes scientific research, is funding this study. This organization is providing money to UTHSA 
Sam and Ann Barshop Institute for Longevity and Aging Studies so that the researchers can conduct the study. 
 
Purpose of this study – “Why is this study being done?” 
The purpose of the research is to evaluate whether older adults with prediabetes or diabetes can benefit from 
taking a drug called semaglutide (Brand name Ozempic) in addition to lifestyle counseling to improve physical 
function, body composition, and biological markers of aging compared to lifestyle counseling alone.  
 
You are asked to participate in this research study of prediabetes/diabetes and aging. This study specifically 
addresses decreased physical function and lean mass that occurs with insulin resistance aging. The 
researchers hope to learn whether semaglutide in addition to lifestyle counseling can help improve physical 
function, body composition, and biomarkers of aging for treatment of older patients with prediabetes or 
diabetes. This could help influence the types of medications used in the treatment of older adults with insulin 
resistance. 
 
Investigation Use of Drug or Device  
This study involves the use of an investigational drug called semaglutide (brand name Ozempic). 
“Investigational” means that the drug has not yet been approved by the U.S. Food & Drug Administration (FDA) 
for pre-diabetes treatment or for improvement of physical function and biomarkers of aging. This medication is 
approved for use in diabetes and weight management.  
 
This study will compare the effects, good and/or bad, this drug has on people who take it and its effect on 
physical function and muscle mass in older adults with pre-diabetes or diabetes. The safety of this drug in 
humans has been tested in prior research studies; however, some side effects may not yet be known.   


Title of Study: The Effect of GLP1 Receptor Agonists on Physical Function, Body Composition, and Biomarkers of Aging 
in Older Overweight/Obese Adults with Insulin Resistance 
 
22-256H, Cortes, Form D, 08-30-23, AMD.docx 
 
Page 5 of 19 
UT Health San Antonio Research Consent and Authorization Documents (v June 29 2021) 
 
This trial may be registered on www.ClinicalTrials.gov, a publicly available registry of clinical trials. This Web 
site will not include information that can identify you. At most, the Web site will include a summary of the 
results. You can search this Web site at any time.   
 
Information about Study Participants – “Who is participating in this research?” 
You are being asked to be a participant in this study because you are age 65 years of age or older, with a BMI 
greater than or equal to 27 kg/m2 and have prediabetes or diabetes.  
 
How many people are expected to take part in this study? This study will enroll approximately 20 study 
participants. 
 
Information about Study Procedures – “What will be done if you decide to be in the research?” 
While you are taking part in this study, you will be asked to attend approximately 8 visits with the researchers 
or study staff over approximately 6 months. You will spend between 1 and 4 hours at each visit, depending on 
the procedures being done. It may be necessary for you to return to clinic every 2-4 weeks during the study. All 
in-person visits will occur at Barshop Institute for Longevity and Aging Studies.  
 
Study Procedures- as a participant, you will undergo the following procedures: 
 
Visit 1, Screening and Baseline Testing, Research only 
This visit will take approximately 2 hours and will occur at the Barshop Institute. You will be asked to arrive 
fasting to the research unit for this visit. After the consent is signed, you will undergo screening and baseline 
testing procedures as outlined below. The results of the screening exams, tests, and/or procedures will be 
reviewed to determine whether you will be allowed to continue in the study. If you are not allowed to continue 
in the study, the researcher will discuss the reasons with you.  If screening lab test results are abnormal, the 
investigator will make a clinical decision whether to repeat the tests and when that should occur.  
 
Outline of visit  
 Informed Consent- We will review all details of the research program in private. You will be provided 
with adequate time to have your questions answered, concerns addressed or clarified, and for you to 
consider whether or not you wish to participate. You will be given a copy of the informed consent to 
keep. 
 Medical history & physical exam/assessment 
o Routine vital signs like blood pressure, heart rate, height, weight, etc will be obtained.   
o Detailed medical history including illnesses, surgeries, social habits, medications and allergies 
will be obtained. 
o Physical exam similar to one at your primary physician’s office will performed.  
 Electrocardiography (ECG)- a test used to evaluate your heart’s electrical function. Stickers are put 
on your skin on your chest, arms and legs; these stickers have electrodes that are connected to the 
machine by lead wires.  
 Screening labs- a blood draw, approximately 2 tablespoons, will be drawn and used to assess your 
general health status. The following blood tests will be performed: 
o Complete blood count (CBC) with differential  
o Comprehensive metabolic panel (CMP) 
o Lipid panel  
o Hemoglobin A1c (HbA1c, a 3-month average reading of blood glucose levels) 
o Thyroid stimulating hormone (TSH, an indicator of your thyroid function) 
o Coagulation test (PT/PTT/INR) to assess how fast your blood will clot 
 Physical function testing, which will include:  
o Balance when standing   
o Distance able to walk over a period of 6 minutes 


Title of Study: The Effect of GLP1 Receptor Agonists on Physical Function, Body Composition, and Biomarkers of Aging 
in Older Overweight/Obese Adults with Insulin Resistance 
 
22-256H, Cortes, Form D, 08-30-23, AMD.docx 
 
Page 6 of 19 
UT Health San Antonio Research Consent and Authorization Documents (v June 29 2021) 
 
o Time it takes to walk about 10 feet  
o Time it takes for you to quickly stand up from a chair and sit down on a chair multiple times  
o Grip strength using an instrument called a dynamometer that measures strength when you 
squeeze as hard as you can 
 DXA scan– we will measure the total amount of fat and muscle in your body by a technique called 
Dual Energy X-ray Absorptiometry. During this procedure, which will last about 10 minutes, you will 
lie on an imaging table while an x-ray camera passes over your body from head to foot. The distance 
between the camera and your body will be about two feet. During the DXA study, you will have to lie 
flat on your back. You will receive a small amount of radiation during the test.  
 Completing a quality of life and appetite survey.  
 
This appointment for Visit 1 will take about 2 hours. 
 
Visit 2 (Day 0), Research only 
Eligible participants asked to arrive fasting to the Barshop Institute research unit to undergo the following: 
 Vital signs – typical assessments like blood pressure, heart rate, respiration rate, and temperature  
 Blood draw – Similar to blood draw at Visit 1. Approximately 2 tablespoons will be drawn for 
research-only to analyze blood markers that are thought to be related to aging. 
 Muscle biopsy  
o We will take 1-2 small samples of your thigh muscle using a special needle. These are called 
muscle biopsies. 
o To do this, we will clean your thigh and inject a local anesthetic (numbing medicine like your 
dentist uses) to numb a small area of your skin. We may have to shave a small area for the 
incision. We will clean the area with a special antiseptic solution. Next, we will make a small cut 
in your skin (about ¼ inch). The biopsy needle will then be passed through this cut into the 
muscle and a piece of muscle tissue about the size of a pea will be obtained. At the time the 
muscle is obtained, many people feel pressure and a thumping sensation. About a third of 
people feel cramping or pressure. The pain is mild to moderate and lasts 30 seconds. The pain 
stops when the needle is removed but your muscle may be sore for a few days. 
o In the areas where the biopsies were done, we will apply strips of adhesive tape (Steri-strips®) 
that will help the skin to close. The adhesive tape will come off on its own, and you do not need 
to peel it off. If you know you are allergic to adhesives used in these types of devices, we can 
suture your skin and have you return to remove the stitches.  
 Fat biopsy   
o We will take 1-2 small samples of fatty tissue about the size of a grape from the area on your 
belly below the navel level. This is called a fat biopsy.  
o To do this, we will clean an area on your belly below navel level and inject a local anesthetic 
(numbing medicine like the dentist uses) to numb the area first. We will clean the area with a 
surgical-grade antiseptic solution.  
o Next, we will make a small cut in your skin (about ¼ inch) of the numb area to administer more 
numbing solution in a technique known as infiltration (spreading the numbing solution under the 
skin across an area about the size of the span of your fingers).  
o Using an instrument that looks like a narrow straw (called a cannula) we will connect the 
instrument to the suction apparatus to collect tissue in a manner similar to a liposuction 
procedure.  
o After the sample is obtained, we will apply a bandage and cover it for protection. We will instruct 
you how to care for the wound. 
 Assignment to Study Groups:  
o You will be randomized, assigned by chance (flipping a coin), to one of two study groups. 


Title of Study: The Effect of GLP1 Receptor Agonists on Physical Function, Body Composition, and Biomarkers of Aging 
in Older Overweight/Obese Adults with Insulin Resistance 
 
22-256H, Cortes, Form D, 08-30-23, AMD.docx 
 
Page 7 of 19 
UT Health San Antonio Research Consent and Authorization Documents (v June 29 2021) 
 
 
Study group 1 will take the study drug (open label), semaglutide (Ozempic), starting at 
0.25 mg subcutaneous injection with titration up to 1 mg per week plus standard lifestyle 
counseling, -or- 
 
Study group 2 will receive standard lifestyle counseling without a study drug. 
 Everyone will have lifestyle counseling. This will be focused on education about healthy eating and 
physical activity. Throughout the study, these visits may be conducted in person, by video or phone.  
 Specifically for study group 1 (study medication plus lifestyle counseling): 
 
You will be supplied the medication at this visit and taught how to self-administer the 
subcutaneous injection of semaglutide 0.25 mg.  
 
You will be monitored on your first self-injection. 
 
You will be started on the medication.  
 
Your appointment for Visit 2 will take about 2-3 hours. 
 
Visit 3 (Approximately week 3), Research only 
 Vital signs – Typical assessments like blood pressure, heart rate, respiration rate, temperature, 
weight  
 Assessment of adverse events- We will ask you if you have had any (unexpected) medical 
experiences (events) since the last visit.  
 Continuation of lifestyle counseling  
 Specifically for study group 1 (study medication plus lifestyle counseling) 
o Study medication will be distributed.  
o We will review how well you have been able to take the medication and review administration 
self-injection instructions.  
o Depending on how you tolerate the medication, we will instruct you how to increase the dose of 
semaglutide to 0.5 mg.  
 
Your appointment for Visit 3 will take about an hour. 
 
Visit 4 (Approximately week 7), Research only 
 Vital signs – typical assessments like height, weight, blood pressure, heart rate, respiration rate, and 
temperature  
 Assessment of adverse events- we will ask you if you have had any (unexpected) medical 
experiences (events) since the last visit.  
 Continuation of lifestyle counseling  
 Specifically for study group 1 (study medication plus lifestyle counseling) 
o Study medication will be distributed.  
o We will review how well you have been able to take the medication and review administration 
self-injection instructions.  
o Depending on how you tolerate the medication, we will instruct you how to increase the dose of 
semaglutide to 1 mg.  
 
Your appointment for Visit 4 will take about an hour. 
 
Visit 5 (Approximately week 11), Research only 
 Vital signs – typical assessments like height, weight, blood pressure, heart rate, respiration rate, and 
temperature  
 Assessment of adverse events- we will ask you if you have had any (unexpected) medical 
experiences (events) since the last visit.  
 Continuation of lifestyle counseling  
 Specifically for study group 1 (study medication plus lifestyle counseling) 


Title of Study: The Effect of GLP1 Receptor Agonists on Physical Function, Body Composition, and Biomarkers of Aging 
in Older Overweight/Obese Adults with Insulin Resistance 
 
22-256H, Cortes, Form D, 08-30-23, AMD.docx 
 
Page 8 of 19 
UT Health San Antonio Research Consent and Authorization Documents (v June 29 2021) 
 
o Study medication will be distributed.  
o We will review how well you have been able to take the medication and review administration 
self-injection instructions.  
o Depending on how you tolerate the medication, we will either continue or decrease the 
semaglutide dose.  
 
Your appointment for Visit 5 will take about an hour. 
 
Visit 6a (Approximately week 20), Research only  
Participants asked to arrive fasting to the Barshop Institute research unit to undergo the following:  
 Physical exam/assessment 
o Routine vital signs like blood pressure, heart rate, height, weight, etc will be obtained.   
o Physical exam similar to one at your primary physician’s office will performed. 
 Assessment of adverse events- we will ask you if you have had any (unexpected) medical 
experiences (events) since the last visit.  
 Blood draw - Similar to blood draw at Visit 1. Approximately 2 tablespoons will be drawn to assess 
your general health status. The following lab tests will be performed:  
o Complete blood count (CBC) with differential  
o Comprehensive metabolic panel (CMP) 
o Lipid panel  
o Hemoglobin A1c (HbA1c, a 3-month average reading of blood glucose levels) 
o Thyroid stimulating hormone (TSH, an indicator of your thyroid function) 
o Coagulation test (PT/PTT/INR) to assess how fast your blood will clot 
 Physical function testing which will include:  
o Balance when standing   
o Distance able to walk over a period of 6 minutes 
o Time it takes to walk about 10 feet  
o Time it takes for you to quickly stand up from a chair and sit down on a chair multiple times  
o Grip strength using an instrument called a dynamometer that measures strength when you 
squeeze as hard as you can 
 DXA scan – we will measure the total amount of fat and muscle in your body by a technique called 
Dual Energy X-ray Absorptiometry. During this procedure, which will last about 10 minutes, you will 
lie on an imaging table while an x-ray camera passes over your body from head to foot. The distance 
between the camera and your body will be about two feet. During the DXA study, you will have to lie 
flat on your back. You will receive a small amount of radiation during the test.  
 Completing a quality of life and appetite survey.  
 
Your appointment for Visit 6a will take about two hours. 
 
Visit 6b (Approximately week 20), Research only 
Participants asked to arrive fasting to the Barshop Institute research unit to undergo the following:  
 Vital signs – typical assessments like blood pressure, heart rate, respiration rate, and temperature  
 Assessment of adverse events- we will ask you if you have had any (unexpected) medical 
experiences (events) since the last visit.  
 Blood draw – Similar to blood draw at Visit 2. Approximately 2 tablespoons will be drawn for 
research-only to analyze blood markers that are thought to be related to aging. 
 Muscle biopsy  
o We will take 1-2 small samples of your thigh muscle using a special needle. These are called 
muscle biopsies. 
o To do this, we will clean your thigh and inject a local anesthetic (numbing medicine like your 
dentist uses) to numb a small area of your skin. We may have to shave a small area for the 


Title of Study: The Effect of GLP1 Receptor Agonists on Physical Function, Body Composition, and Biomarkers of Aging 
in Older Overweight/Obese Adults with Insulin Resistance 
 
22-256H, Cortes, Form D, 08-30-23, AMD.docx 
 
Page 9 of 19 
UT Health San Antonio Research Consent and Authorization Documents (v June 29 2021) 
 
incision. We will clean the area with a special antiseptic solution. Next, we will make a small cut 
in your skin (about ¼ inch). The biopsy needle will then be passed through this cut into the 
muscle and a piece of muscle tissue about the size of a pea will be obtained. At the time the 
muscle is obtained, many people feel pressure and a thumping sensation. About a third of 
people feel cramping or pressure. The pain is mild to moderate and lasts 30 seconds. The pain 
stops when the needle is removed but your muscle may be sore for a few days. 
o In the areas where the biopsies were done, we will apply strips of adhesive tape (Steri-strips®) 
that will help the skin to close. The adhesive tape will come off on its own, and you do not need 
to peel it off. If you know you are allergic to adhesives used in these types of devices, we can 
suture your skin and have you return to remove the stitches.  
 Fat biopsy   
o We will take 1-2 small samples of fatty tissue about the size of a grape from the area on your 
belly below the navel level. This is called a fat biopsy.  
o To do this, we will clean an area on your belly below navel level and inject a local anesthetic 
(numbing medicine like the dentist uses) to numb the area first. We will clean the area with a 
surgical-grade antiseptic solution.  
o Next, we will make a small cut in your skin (about ¼ inch) of the numb area to administer more 
numbing solution in a technique known as infiltration (spreading the numbing solution under the 
skin across an area about the size of the span of your fingers).  
o Using an instrument that looks like a narrow straw (called a cannula) we will connect the 
instrument to the suction apparatus to collect tissue in a manner similar to a liposuction 
procedure.  
o After sample is obtained, we will apply a bandage and cover it for protection. We will instruct 
you how to care for the wound. 
 
Visit 7 (Approximately week 21), Research only 
 The last visit can be in person or a televisit (phone or virtual) to ensure that you are doing well after 
visit 6a and visit 6b.  
 
Visit Schedule Summary 
 
T - (1 
wk 
±7d) 
T =0 
T (3w 
± 7d) 
T (7w 
± 7d) 
T 
(11w ± 
7d)  
T (20w 
± 7d) 
T (20w 
± 7d) 
T (21w 
± 7d)  
Visit # 
V1 
V2 
V3 
V4 
V5 
V6a 
V6b 
V7 
History and physical exam 
X 
 
 
 
 
X 
 
 
Vitals, anthropometric 
measurements 
X 
X 
X 
X 
X 
X 
X 
 
Clinical labs 
X 
 
 
 
 
X 
 
 
Randomization  
 
X 
 
 
 
 
 
 
DXA scan 
X 
 
 
 
 
X 
 
 
ECG 
X 
 
 
 
 
 
 
 
SPPB, grip strength, 6-minute 
walk 
X 
 
 
 
 
X 
 
 
Surveys (SF-12, CNAQ) 
X 
 
 
 
 
X 
 
 
Blood, muscle, and adipose biopsy   
X 
 
 
 
 
X 
 
Semaglutide dispensed to 
treatment group 
 
X 
X 
X 
X 
 
 
 
In-person lifestyle education 
 
X 
X 
X 
X 
 
 
 
Assessment for adverse events  
 
 
X 
X 
X 
X 
X 
X 
 


Title of Study: The Effect of GLP1 Receptor Agonists on Physical Function, Body Composition, and Biomarkers of Aging 
in Older Overweight/Obese Adults with Insulin Resistance 
 
22-256H, Cortes, Form D, 08-30-23, AMD.docx 
 
Page 10 of 19 
UT Health San Antonio Research Consent and Authorization Documents (v June 29 2021) 
 
Future Use of Your Information or Biospecimens Collected as Part of Your Participation 
Identifiers may be removed and the de-identified information or biospecimens could be used for future 
research studies or distributed to another investigator for future research studies without additional informed 
consent from you or your legally authorized representative.  
 
Your biospecimens, even if identifiers are removed, may be used for commercial profit and you would not 
share in this commercial profit. 
 
Research involving your biospecimens might include whole genome sequencing. Whole genome sequencing is 
the process of determining the complete DNA sequence of a person or other organism’s genome at a single 
time.  DNA is short for deoxyribonucleic acid. DNA contains information that determines in part the traits, such 
as eye color, height, or disease risk, that are passed on from parent to child. 
 
Return of Research Test Results for Genetic Tests to Subjects 
It is possible that this study will identify information about you that was previously unknown, such as disease 
status or risk.   
 
There are no plans to provide this information to you or your physician unless the information indicates that you 
may be at risk for a serious illness known at the time of testing to be treatable and it can be confirmed by a 
clinical laboratory.  In that case, we will attempt to notify you using the contact information you have provided 
and discuss recommended follow up.  
 
Information about Optional Procedures – “What are other research activities that may be done but 
are not required for your participation?” 
E-mail Authorization Agreement  
The research team would like to communicate with you regarding your research visits via email, which uses an 
“encrypted” method for secure transmission.  When one of the research team sends you an email, you will 
receive an email that says “[SECURE MESSAGE]” from a research team member with a link to open the 
message. When you click on the link it will take you to a secure website where you can read the message and 
reply after successful authentication. 
If you are not able to receive email, you may not be eligible to participate in the study. 
 
Texting  
The research team would like to communicate with you regarding your participation via text message.  These 
messages may include information related to your participation in the study and payment information, if 
applicable.  In order to do this, we will share your name and phone number with Tiger Connect. Standard text 
messaging rates will apply if you do choose to receive the text messages. 
 
If you are not able to receive texts, you may not be eligible to participate in the study. 
 
Ending Participation Early 
Could your participation end early? There are several reasons why the researchers may need to end your 
participation in the study (early withdrawal).  Some reasons are: 
• 
The researcher believes that it is not in your best interest to stay in the study. 
• 
You become ineligible to participate. 
• 
Your condition changes and you need treatment that is not allowed while you are taking part in the study. 
• 
You do not follow instructions from the researchers. 
• 
The study is stopped. 
 
The researchers will discuss your options for medical care when your participation in this study ends. 
 


Title of Study: The Effect of GLP1 Receptor Agonists on Physical Function, Body Composition, and Biomarkers of Aging 
in Older Overweight/Obese Adults with Insulin Resistance 
 
22-256H, Cortes, Form D, 08-30-23, AMD.docx 
 
Page 11 of 19 
UT Health San Antonio Research Consent and Authorization Documents (v June 29 2021) 
 
 
Risks – “What are the risks of participation in the research?” 
 
Risks from the specific research procedures (drug(s), interventions, or procedures) 
The following section will describe the risks related to your participation in this research study.  One risk is that 
you may have side effects while on the study. Side effects can range from mild to serious. Serious side effects 
are those that may require hospitalization, are life-threatening or fatal (could cause death). The frequency that 
people experience a certain side effect can range from many (likely), few (less likely) or only one or two 
(rarely).  
 
Side effects from this study will usually go away soon after you stop taking the study drug. In some cases, side 
effects can be long-lasting or may never go away.  
 
Everyone taking part in the study will be watched carefully for any side effects. However, the study doctors 
may not know all the side effects that may happen. Be sure to tell your study doctor immediately, about any 
side effect that you have while taking part in the study.  
 
The following section will describe the risks related to each drug, intervention or procedure that is part of this 
research study. You should talk to your study doctor about any side effects or other problems that you have 
while taking part in the study.  
 
Risks and side effects related to the study include those which are:  
 
Questionnaire data collection  
Less Likely (less than 5-30 subjects out of 100) and Not Serious: 
• 
Uncomfortable answering questions –If you feel uncomfortable answering questions, one of the 
investigators will speak with you to help clarify your doubts. Your responses will be kept confidential. You 
do not have to respond to any question that you do not feel comfortable answering.  
 
Rare (less than 5 subject out of 100) and Serious: 
• 
Breach of confidentiality- It is possible in a rare occurrence there may be a breach of confidentiality.  
However, researchers have taken steps to minimize this risk such as keeping records and materials in a 
secure, locked location. 
 
Physical function testing exam/assessment  
Not Serious and Less Likely (less than 5-30 subjects out of 100):  
• 
Brief, temporary fatigue with balance test, walking 10-ft and/or using handheld dynamometer to measure 
grip strength 
 
Needlestick blood draw: 
Likely, and may not be serious (5-30 subjects out of 100): 
• 
Some people experience bleeding, bruising or swelling at the site of the needle entry. Fainting or 
lightheadedness may also occur. A qualified phlebotomist will perform your blood draw to reduce the risk of 
this happening. 
 
Less likely, and may or may not be serious (1-5 subjects in 100): 
• 
Bleeding may occur outside of the blood vessels (hematoma/bruise). 
 
Rare, and may or may not be serious (less than 1 in 100 needlestick procedures): 
• 
There is a small risk of infection and nerve damage at the needle entry site. 
 


Title of Study: The Effect of GLP1 Receptor Agonists on Physical Function, Body Composition, and Biomarkers of Aging 
in Older Overweight/Obese Adults with Insulin Resistance 
 
22-256H, Cortes, Form D, 08-30-23, AMD.docx 
 
Page 12 of 19 
UT Health San Antonio Research Consent and Authorization Documents (v June 29 2021) 
 
Catheter blood draw: 
Not serious and Less Likely (less than 1 in 100):  
• 
During the study, catheters may be inserted into the veins in your arm to facilitate blood draw and reduce 
number of needlesticks. Some people experience mild pain from the catheter.  
• 
There is a small risk of bleeding when veins are punctured, and a catheter is placed into the vein.  
• 
Bleeding will be seen as bruising (black and blueness) at the place where the blood was obtained. The 
bruising usually goes away within 3 to 4 days, although sometimes it may take a week. The bruising is 
helped by using hot packs.  
• 
There is a small risk of infection where your veins are punctured.  
 
Muscle biopsy:  
Less likely and not serious (1-2 subjects in 100):  
• 
At the time the muscle is obtained, most people feel a pressure sensation, and some people feel a 
thumping sensation.  
• 
People might feel cramping, pain or soreness. In the people who feel cramping, pain or soreness, this will 
usually be mild to moderate in severity and will last approximately 30 seconds. The pain stops when the 
needle is removed, but your muscle may be sore for a few days.  
• 
Bleeding from a muscle biopsy may occur and will be seen as bruising at the place on your leg where we 
take the muscle. The swelling or bruising usually goes away with rest within 2-3 days, although sometimes 
it may take a week. The bruising is reduced by using hot packs.  
 
Rare and Serious (less than 1 in 500 of these procedures):  
• 
Rarely, bleeding from a muscle biopsy may be severe enough to require hospitalization. 
 
Rare and Serious (less than 1 in 1,000): 
• 
Very rarely, some subjects may experience numbness or tingling at the biopsy site. This usually is 
temporary and goes away in a few days. There is the possibility that nerve damage could be permanent.  
 
Rare and Serious (less than 1 in 100): 
• 
There is a small risk of infection at the site of the muscle biopsy. Symptoms of an infection would include 
pain, redness, swelling, and yellow-greenish (pus-looking) discharge in the biopsy site, and is usually 
accompanied by fever. Because multiple biopsies of the muscle may be performed, the risk of infection and 
pain in the leg may increase. Infections can be usually treated effectively with antibiotics taken by mouth. In 
very rare occasions, hospitalization is required to give antibiotics through the vein, and an operation could 
be needed to clean the infected area.  
• 
Allergic reactions to the local anesthetic we use for the muscle biopsy are extremely rare, but could include 
a skin sore, swelling, or hives.  
 
There is the possibility that a future biopsy may not be done at the discretion of the PI in case the subject did 
not tolerate well a prior biopsy. 
 
Adipose biopsy:  
Likely and not serious: 
• 
Numbness in the area 
• 
Scar of ~5mm for each incision 
• 
Bleeding from an adipose biopsy may occur and will be seen as bruising at the place on your abdomen 
where we take the adipose sample. The swelling or bruising usually goes away with rest within 2-3 days, 
although sometimes it may take a week. 
Less likely and not serious:  
• 
Moderate pain at the site where the sample was collected 
• 
Skin irritation at the site of the bandage 


Title of Study: The Effect of GLP1 Receptor Agonists on Physical Function, Body Composition, and Biomarkers of Aging 
in Older Overweight/Obese Adults with Insulin Resistance 
 
22-256H, Cortes, Form D, 08-30-23, AMD.docx 
 
Page 13 of 19 
UT Health San Antonio Research Consent and Authorization Documents (v June 29 2021) 
 
• 
Reaction to the medication (Lidocaine) used to numb the area 
 
Less Likely and serious (less than 1 in 100): 
• 
Infection at the site where the sample was collected. 
 
Radiation exposure for body composition (DXA) 
Participation in this research study involves exposure to radiation from medical imaging (ex: Fluoroscopy, CT, 
PET, Nuclear Medicine scan). Every member of the general public receives approximately 310 mrem (a unit of 
radiation exposure) every year from natural sources, including cosmic radiation and radiation naturally found in 
our environment.  Current evidence and research suggest that the risks of medical imaging at radiation doses 
below 10,000 mrem are too low to be detectable and may be nonexistent (American Association of Physicists 
in Medicine Policy PP 25, Health Physics Society Position Statement PS010-4). The total amount of radiation 
exposure that you are anticipated to receive from the procedures associated with your participation in this 
research study is 0.2 mrem, which is less than the amount of radiation exposure a member of the general 
public receives from natural sources per year on average. 
 
If you have had prior radiation therapy (such as for cancer), or have any questions regarding radiation and its 
risks, please reach out to the Radiation Safety Office who can put you in touch with someone who can help 
address your concerns. 
 
Semaglutide 
The following are the risks possibly associated with treatment of Semaglutide (Brand name Ozempic): 
 
Less likely and not serious (5-20 subjects out of 100): 
• 
Nausea 
• 
Vomiting  
• 
Diarrhea  
• 
Abdominal pain  
• 
Constipation 
• 
Indigestion  
• 
Gastritis (Inflammation of the lining of the stomach) 
• 
Decreased appetite 
• 
Increased flatulence (passing gas) 
• 
Fatigue  
• 
Headache  
• 
Change in taste  
 
Less likely and serious (1-4 subjects out of 100): 
• 
Low blood sugar (also called Hypoglycemia)  
• 
Gallbladder disease  
• 
Worsening of diabetic retinopathy (eye condition that can cause vision loss and blindness) 
• 
Injection site reactions  
• 
Low blood pressure  
• 
Dizziness  
• 
Developing antibodies to Semaglutide  
 
Rare and serious: 
• 
Acute kidney injury  
• 
Hypersensitivity reactions such as anaphylaxis and angioedema (allergic reactions) 
• 
Acute pancreatitis including hemorrhagic pancreatitis and necrotizing pancreatitis  


Title of Study: The Effect of GLP1 Receptor Agonists on Physical Function, Body Composition, and Biomarkers of Aging 
in Older Overweight/Obese Adults with Insulin Resistance 
 
22-256H, Cortes, Form D, 08-30-23, AMD.docx 
 
Page 14 of 19 
UT Health San Antonio Research Consent and Authorization Documents (v June 29 2021) 
 
• 
Medullary thyroid carcinoma was seen in animal trials with other medications, not Semaglutide, in the 
glucagon-like peptide (GLP-1) receptor agonist class and medullary thyroid cancer has been reported in 
patients taking liraglutide (a similar medication).   
 
Acute events of gallbladder disease such as cholelithiasis (gallstone formation) or cholecystitis (inflammation of 
the gallbladder) have been reported in GLP-1 receptor agonist trials and postmarketing. In placebo-controlled 
trials, cholelithiasis was reported in 1.5% and 0.4% of patients-treated with Ozempic 0.5 mg and 1 mg, 
respectively. Cholelithiasis was not reported in placebo-treated patients.  
 
Electrocardiogram (ECG): 
Rare and not Serious (5 or fewer subjects out of 100): 
• 
Mild skin irritation (e.g., itching, rash), occurring where the electrodes are stuck on the skin 
• 
Discomfort from lying in one position for 5 – 10 minutes while the ECG is being recorded 
 
Genetic Informational risks related to the study 
This study may include genetic testing.  Human tissue contains genes that determine many of a person’s 
physical characteristics, such as the color of eyes and hair.  In some cases, genetic testing of tissues can be 
used to indicate a risk for the development of certain diseases.  Genetic information is unique to each 
individual and could potentially be used to discover possible changes in a person’s future health status or life 
expectancy, or that of his/her children and family members. Even if your tissues are used for this type of 
research, the results will not be put in your health records. Releasing this information to you could cause 
psychological distress, anxiety or family problems.   
 
Releasing this information to others, such as including it in your medical record, may pose a possible risk of 
discrimination, or increase difficulty in obtaining or maintaining disability, long-term care, or life insurance.   
 
These risks would occur if your information is released by mistake.  The measures being taken to protect your 
privacy are discussed below and make this possibility unlikely. 
 
Even though the results of genetic testing may not be linked to you, it is possible that people of your ethnic 
background may be found to be at more risk for certain diseases based on future genetic research and this 
information might harm you in the future as a member of the group. Also, there may be unknown risks of 
genetic testing in the future. 
 
Changes to medications  
Please immediately inform the study team when a new medication or supplement is started, as this may 
increase the risk of having an adverse event.  
 
Are there Risks related to withdrawing from the study?  
If you decide to withdraw from this study early, please discuss your decision with the principal investigator.  
The researcher may ask you to complete study withdrawal procedures at a final study visit.  This visit includes 
the procedures in visit 6a, 6b, and 7.  There is no risk to you if you do not complete the final withdrawal 
procedures and you can choose not to participate in them. 
 
Are there risks if you also participate in other research studies? 
Being in more than one research study at the same time may increase the risk to you.  It may also affect the 
results of the studies.  You should not take part in more than one study without approval from the researchers.   
 
What if a research-related injury occurs?  
The researchers have taken steps to minimize the known or expected risks.  However, you may still 
experience problems or side effects, even though the researchers are careful to avoid them.  In the event of a 


Title of Study: The Effect of GLP1 Receptor Agonists on Physical Function, Body Composition, and Biomarkers of Aging 
in Older Overweight/Obese Adults with Insulin Resistance 
 
22-256H, Cortes, Form D, 08-30-23, AMD.docx 
 
Page 15 of 19 
UT Health San Antonio Research Consent and Authorization Documents (v June 29 2021) 
 
research-related injury or if you experience an adverse reaction, please immediately contact your study doctor.  
See the section “Contact Information” for phone numbers and additional information.  You may also need to tell 
your regular doctors. 
 
If you are injured or made sick from taking part in this research study, medical care will be provided. This care 
may be billed to you or your insurance. Depending on the circumstances, this care may be provided at no cost 
to you. We have no plans to give you money if you are injured. The investigator can provide you with more 
information. 
 
If you sign this form, you do not give up your right to seek additional compensation if you are harmed as a 
result of being in this study. 
 
Benefits – “How could you or others benefit from your taking part in this study?” 
There is no guarantee or promise that you will receive any benefit from this study.  However, the possible 
benefit of your participating in this study is to receive health information such as lab results related to your 
blood sugar, information on your body composition, and education on lifestyle modifications. 
 
We hope the information learned from this study will benefit other people with similar conditions in the future.  
Physical function decline and loss of muscle mass are commonly seen in older adults, especially those with 
insulin resistance. Your participation may benefit future patients by helping us gain valuable information for 
conditions that affect a majority of older adults.  
 
Alternative procedures or course of treatment – “What other options are there to participation in this 
study?” 
Your other option would be to not participate in this study.   
 
Payments – Will there be any payments for participation? 
The researchers will provide you with a MasterCard®.  Compensation will be automatically credited after 
completion of each visit.  Your name, address, date of birth, and social security number will be shared with a 
third-party solely for the purposes of compensation processing.  This information will only be used for the 
administration of the compensation (ClinCard) and will be kept strictly confidential. The payment schedule is as 
follow:  
Visit 1 
$50 
Visit 2 
$125 
Visit 3 
$20 
Visit 4 
$20 
Visit 5 
$20 
Visit 6a 
$50 
Visit 6b 
$125 
Visit 7 
$15 
 
The total you may receive if you completed all visits for this study is up to $425.  
 
 
Costs – Will taking part in this study cost anything? 
The Principal Investigator will provide the study drug/device free of charge during this study. At the end of your 
participation, you must return all unused study drug/device to the researcher.   
 
There is no direct cost to participating in the study.  
 
 


Title of Study: The Effect of GLP1 Receptor Agonists on Physical Function, Body Composition, and Biomarkers of Aging 
in Older Overweight/Obese Adults with Insulin Resistance 
 
22-256H, Cortes, Form D, 08-30-23, AMD.docx 
 
Page 16 of 19 
UT Health San Antonio Research Consent and Authorization Documents (v June 29 2021) 
 
Confidentiality – How will your records be kept confidential? 
Information we learn about you in this study will be handled in a confidential manner, within the limits of the 
law.  If we publish the results of the study in a scientific journal or book, we will not identify you.  The 
Institutional Review Board and other groups that have the responsibility of monitoring research may want to 
see study records which identify you as a subject in this study.   
 
To help us protect your privacy, we have obtained a Certificate of Confidentiality from the Federal Government. 
With this Certificate, the researchers cannot be forced to disclose, in any federal, state, or local civil, criminal, 
administrative, legislative, or other proceedings or any other person not connected to the research,  your (or 
your family member’s) name or any of such individual or any such information, document, or biospecimen that 
contains identifiable, sensitive information about the individual and that was created or compiled for purposes 
of the research, that may identify you, even by a court subpoena, in any federal, state, or local civil, criminal, 
administrative, legislative, or other proceedings. 
 
The researchers will use the Certificate to resist any demands for information that would identify you, except as 
explained below.  The Certificate cannot be used to resist a demand for information from personnel of the 
United States Government that is used for auditing or evaluation of federally funded projects or for information 
that must be disclosed in order to meet the requirements of the federal Food and Drug Administration (FDA).  
You should understand that a Certificate of Confidentiality does not prevent you or a member of your family 
from voluntarily releasing information about yourself or your involvement in this research.  If an insurer, 
employer, or other person obtains your written consent to receive research information, then the researchers 
may not use the Certificate to withhold that information. 
 
The Certificate of Confidentiality does not prevent the researchers from disclosing voluntarily, without your 
consent, information that would identify you as a participant in the research project under certain 
circumstances.  Circumstances that warrant the release of your information without your permission include: 
abuse and/or neglect, intention to harm yourself or others, or certain communicable diseases, or other 
scientific research that is in compliance with applicable Federal regulations governing the protection of human 
participants in research.  Should you require medical treatment as it relates to the information, document, or 
biospecimen pertains, additional consent will be obtained. 
 
Limits of Confidentiality 
Even without your consent, suspected or known abuse or neglect of a child, disabled, or elder abuse, 
threatened violence to self or others or other local health reporting requirements will be reported to appropriate 
authorities. 
 
Research policies require that private information about you be protected and this is especially true for your 
health information.  However, the law sometimes allows or requires others to see your information.  The 
information given below describes how your privacy and the confidentiality of your research records will be 
protected in this study. 
 
What is Protected Health Information (PHI)?   
Protected Health Information is information about a person’s health that includes information that would make it 
possible to figure out whose it is.  According to the law, you have the right to decide who can see your 
protected health information.  If you choose to take part in this study, you will be giving your permission to the 
investigators and the research study staff (individuals carrying out the study) to see and use your health 
information for this research study.  In carrying out this research, the health information we will see and use 
about you will include: medical history, blood work, information gathered from your medical record if available, 
treatments prior to the study, information you provide during participation in the study, results of blood tests, 
and demographic information like your age, marital status, and race or ethnicity. 
 


Title of Study: The Effect of GLP1 Receptor Agonists on Physical Function, Body Composition, and Biomarkers of Aging 
in Older Overweight/Obese Adults with Insulin Resistance 
 
22-256H, Cortes, Form D, 08-30-23, AMD.docx 
 
Page 17 of 19 
UT Health San Antonio Research Consent and Authorization Documents (v June 29 2021) 
 
We will get this information by asking you, asking your doctor, and/or looking at your electronic medical record 
if one is available through the UT Health San Antonio system.    
 
How will your PHI be shared?   
Because this is a research study, we will be unable keep your PHI completely confidential.  We may share your 
health information with people and groups involved in overseeing this research study including: 
 
• 
The National Institutes of Health (NIH), National Institute of Aging (NIA) who is funding the study 
• 
The UT Health San Antonio Claude D. Pepper Older Americans Center, where the study is being 
conducted  
• 
The company that provides the study drug (Medplus) 
• 
The UT Health San Antonio Claude D. Pepper Older Americans Center Data and Safety Monitoring 
Board, which is the committee that checks the study data and safety on an ongoing basis, to determine 
if the study should be stopped for any reason  
• 
The members of the local research team  
• 
The Institutional Review Board and the Compliance Office of the University of Texas Health Science 
Center at San Antonio, and other groups that oversee how research studies are carried out. 
• 
The Research offices at UT Health San Antonio  
• 
The Food and Drug Administration (FDA) and other U.S. and international governmental regulatory 
agencies involved in overseeing drug research  
 
If you decide to participate in this study, you will be giving your permission for the groups named above, to 
collect, use and share your health information.  If you choose not to let these groups collect, use and share 
your health information as explained above, you will not be able to participate in the research study. 
 
Parts of your PHI may be photocopied and sent to a central location or it may be transmitted electronically, 
such as by e-mail or fax. The groups receiving your health information may not be obligated to keep it private.  
They may pass information on to other groups or individuals not named here. 
 
How will your PHI be protected?   
In an effort to protect your privacy, the study staff will use code numbers instead of your name, to identify your 
health information.  Initials and numbers will be used on any photocopies of your study records, and other study 
materials containing health information that are sent outside of UT Health San Antonio for review or testing.  If 
the results of this study are reported in medical journals or at meetings, you will not be identified. 
 
Do you have to allow the use of your health information? 
You do not have to allow (authorize) the researchers and other groups to see and share your health 
information.  If you choose not to let the researchers and other groups use your health information, there will 
be no penalties but you will not be allowed to participate in the study.   
 
After you enroll in this study, you may ask the researchers to stop using your health information at any time.  
However, you need to say this in writing and send your letter to: 
 
Tiffany M. Cortes, MD 
4939 Charles Katz Dr.  
San Antonio, TX 78229 
 
If you tell the researchers to stop using your health information, your participation in the study will end and the 
study staff will stop collecting new health information from you and about you for this study.  However, the 
study staff will continue to use the health information collected up to the time they receive your letter asking 
them to stop. 


Title of Study: The Effect of GLP1 Receptor Agonists on Physical Function, Body Composition, and Biomarkers of Aging 
in Older Overweight/Obese Adults with Insulin Resistance 
 
22-256H, Cortes, Form D, 08-30-23, AMD.docx 
 
Page 18 of 19 
UT Health San Antonio Research Consent and Authorization Documents (v June 29 2021) 
 
 
Can you ask to see the PHI that is collected about you for this study?   
The federal rules say that you can see the health information that we collect about you and use in this study.  
Contact the study staff if you have a need to review your PHI collected for this study. 
You will only have access to your PHI until 12/31/2032.  
Because of the type of research, you can only access your PHI when the study is done.  At that time, you have 
the right to see and copy the medical information we collect about you during the study, for as long as that 
information is kept by the study staff and other groups involved.   
 
How long will your PHI be used?   
By signing this form, you agree to let us use and disclose your health information for purposes of the study until 
the end of the study.  This permission to use your personal health information expires when the research ends, 
and all required study monitoring is over. 
 
Contact Information – Who can you contact if you have questions, concerns, comments or 
complaints? 
If you have questions now, feel free to ask us.  If you have additional questions, concerns, comments or 
complaints later or you wish to report a problem which may be related to this study please contact: 
 
Primary contact: 
Tiffany M. Cortes, MD can be reached at 361-244-3747 
 
If primary is not available: 
Sara E. Espinoza, MD can be reached at 210-617-5197 
 
The UT Health San Antonio committee that reviews research on human subjects (Institutional Review Board) 
will answer any questions about your rights as a research subject, and take any concerns, comments or 
complaints you may wish to offer.  You can contact the IRB by calling 210-567-8250, or by mail to IRB, UT 
Health San Antonio, Mail Code 7830, 7703 Floyd Curl Drive, San Antonio, TX  78229-3900. 
 
 
 


Title of Study: The Effect of GLP1 Receptor Agonists on Physical Function, Body Composition, and Biomarkers of Aging 
in Older Overweight/Obese Adults with Insulin Resistance 
 
22-256H, Cortes, Form D, 08-30-23, AMD.docx 
 
Page 19 of 19 
UT Health San Antonio Research Consent and Authorization Documents (v June 29 2021) 
 
Research Consent & Authorization Signature Section 
If you agree to participate in this research and agree to the use of your protected health information in this 
research sign this section.  You will be given a signed copy of this form to keep.  You do not waive any of your 
legal rights by signing this form.   
 
SIGN THIS FORM ONLY IF THE STATEMENTS LISTED BELOW ARE TRUE 
• 
You have read the above information. 
• 
Your questions have been answered to your satisfaction about the research and about the collection, use 
and sharing of your protected health information.   
 
Adult Signature Section 
• 
You have voluntarily decided to take part in this research study. 
• 
You authorize the collection, use and sharing of your protected health information as described in this form. 
 
 
 
 
 
 
 
AM 
PM 
Printed Name of Subject 
 
Signature of Subject 
 
Date 
 
Time 
 
 
 
 
 
 
 
AM 
PM 
Printed Name of Person Obtaining 
Consent and Authorization 
 
Signature of Person Obtaining Consent 
and Authorization 
 
 
Date 
 
Time 
Consent and authorization were obtained from this individual who is unable to read and/or write but can otherwise communicate and/or comprehend 
English.   The method used for communication with the subject was: ______________________.   
The specific means by which the subject communicated agreement to participate was: __________________________________ 
 
 

Prot_SAP_002.pdf: 
 
22-256H, Cortes, Form CT, 03-23-23, AMD.docx 
 
1 
22-256H, Cortes, Form CT, 03-23-23, AMD.Docx 
 
COVER PAGE  
 
 
 
 
 
Official Study Title: The Effect of GLP1 Receptor Agonists on Physical Function, Body 
Composition, and Biomarkers of Aging in Older Overweight/Obese Adults with Insulin 
Resistance 
 
NCT number: NCT05786521 
 
IRB Approval Date: 03.23.2023 
 
 
Unique Protocol ID: 20220256HU 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


 
22-256H, Cortes, Form CT, 03-23-23, AMD.docx 
 
22-256H, Cortes, Form CT, 03-23-23, AMD.Docx  
                            
2 
 
Form CT 
UTHSA Clinical Trial Description 
This form is not mandatory.  Other documents are acceptable if equivalent information is provided. 
UTHSCSA Tracking Number 
(internal use only) 
 
20220256HU 
1. Original Version 
Date 
08-31-22 
 
 
1.1. Revision Date(s)  
add rows as needed 
2.0 
 
 
2. Background 
Briefly discuss the important literature relevant to the trial and that provides background for the trial.  Include the importance of the trial and any relevant 
treatment issues or controversies. 
Approximately 25% of older adults in the U.S. have Type 2 Diabetes (T2D) and nearly 50% have 
prediabetes. The mechanisms that cause age-related glucose intolerance and diabetes are unknown, but 
age-dependent decreases in β-cell function and insulin sensitivity are thought to be important in 
deterioration of glucose homeostasis with age.  There are also changes in body composition with age that 
can contribute to insulin resistance with age, including: (1) redistribution of fat from peripheral and 
subcutaneous to a central location, and (2) loss of lean muscle mass . Thus, most older adults have some 
degree of insulin resistance and mechanisms that contribute to insulin resistance become more pronounced 
with aging.  
The usual comorbidities associated with diabetes are recognized as cardiovascular, renal, and neuropathic 
diseases; however, there are physical function and body composition changes which occur which impact 
aging outcomes. A meta-analysis by Wong et showed that those with diabetes had an increased risk of 
mobility disability, defined by walking speed, chair stand, and balance tests, compared to those without 
diabetes (risk ratio=1.51, 95%CI 1.38-1.64). These physical changes have also been seen in those with 
prediabetes. Over 12 years, those with prediabetes compared to normoglycemia had an increased predicted 
trajectory of chair stand time (p<0.05), decreased walking speed (p<0.01) and an accelerated disability 
progression (p<0.01). In multiple longitudinal studies, older adults with diabetes lost more lean mass 
compared to those without diabetes. Further, the decline of physical function as measured by various 
assessments (balance, walking speed, balance) and sarcopenia, decline of lean body mass, are predictive 
of nursing home admission and death .   
Inflammation is one of the key mechanisms underlying aging and age-related diseases.  Chronic 
inflammation contributes to aging through several complex pathways.  One pathway is cellular senescence, 
which contributes to normal aging, but also to the burden of low-grade chronic inflammation through 
activation of a wide range of growth factors, cytokines and other inflammatory factors. Higher levels of 
inflammation markers, interleukin (IL)-6 and C-reactive protein (CRP), have been demonstrated in 
individuals with insulin resistance as well as T2D, and are also predictors of frailty in older adults.  
GLP1 receptor agonists are generally considered second line treatment for patients with T2D, but this class 
of medications maybe considered first-line in patients who are at high risk for cardiovascular disease or 
already have a history of cardiovascular disease. GLP1 receptor agonists increase insulin and decrease 
glucagon in response to hyperglycemia and suppress appetite likely mediated through actions on receptors 
in the hypothalamus and other areas of the central nervous system. Although weight loss is one of the 
benefits of this class, there is concern that the weight loss observed with GLP1 receptor agonist use is 
accompanied by loss of lean mass in addition to fat mass, which is especially concerning in an older adult 
population who have age-related sarcopenia. A review of the effect of GLP1 receptor agonists on body 
composition showed, as expected, a total body weight loss but the breakdown of weight loss from lean body 
and fat mass varied significantly between the studies. Some showed an increase in lean body mass while 
other showed that a significant portion of the weight loss came from lean body mass, up to 65.2%, in those 
treated with GLP1 receptor agonists T2D. Interestingly in rodent models, GLP1 receptor agonists have 
shown to have beneficial effects on skeletal muscle atrophy. A meta-analysis showed an improvement of the 


 
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pro-inflammatory milieu in patients with T2D treated GLP1 receptor agonists compared to placebo or other 
T2D medications with a significant change of CRP (-0.54mg/L, 95% CI -0.7- -0.34), tumor necrosis factor 
alpha (-0.39, 95% CI -0.62 - -0.15), and adiponectin (0.30, 95% CI 0.12-0.49). Although there are known 
cardiovascular and weight management benefits of GLP1 receptor agonists outside of their ability to treat 
hyperglycemia, information about physical function is understudied especially in older adults. Use of GLP1 
agonists is rapidly increasing, but research in older adults is very limited. This pilot work will be an important 
first step in examining the potential usefulness of GLP1 receptor agonists in older adults to improve glycemic 
control, as well as physical function and lean mass. 
 
 
 
3. Objectives and Endpoints     All data points collected in the study should support an objective or have a regulatory purpose.   
Complete the table – add rows as needed.   
3.1. Objective(s)  
Clearly and concisely define the primary and 
secondary outcomes.  
3.2. Endpoint 
Clearly define the endpoints.  
(endpoints are the basis for concluding that 
the objective has been met). 
3.3. Justification for Endpoint 
Briefly explain why the endpoint(s) were chosen. 
Aim 1: To conduct a pilot study to 
examine the effect of GLP1 
receptor agonists on physical 
function and body composition in 
older overweight/obese adults 
with prediabetes or well controlled 
diabetes. 
Aim 2: To examine the impact of 
GLP1 receptor agonists on 
biomarkers of aging (cellular 
senescence and inflammation) in 
older overweight/obese adults 
with prediabetes or well controlled 
diabetes. 
 
Aim 1: Any change in 
-Short physical performance 
battery (SBBP) 
-Handgrip strength  
-6 minute walking distance  
-BMI 
-Body composition (lean body 
mass to fat mass) 
 
Aim 2:  
-Markers of cellular 
senescence and inflammation 
in muscle, adipose, and blood 
GLP1 receptor agonists are an FDA-
approved class of drugs for the 
treatment of T2D which lead to 
improvement in adiposity but possibly 
at the risk of significant decline on 
lean body mass. Additionally, there is 
a lack of studies to determine if these 
changes are associated with a 
significant change in functional status.  
Therefore, Aim 1 will address the 
specific hypothesis that the GLP1 
receptor agonist semaglutide will 
improve physical function (SPPB, 
handgrip strength, walking speed) and 
body composition (BMI, lean body 
mass to fat mass ratio) compared to 
standard of care. 
Diabetes is known to be pro-
inflammatory state that can promote 
cellular senescence. GLP1 receptor 
agonists have shown positive 
improvement of inflammatory makers 
but this has not been studied 
extensively in older adults.  Therefore, 
Aim 2 will test the hypothesis that the 
GLP1 receptor agonist semaglutide 
(by improving glycemia and adiposity) 
will decrease markers of cellular 
senescence and inflammation in 
muscle, adipose tissue and blood. 
 
 
4. Rationale 
Briefly state the reason for conducting the clinical trial.  


 
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The results of this study will provide useful information which could influence the treatment algorithm for 
older adults with prediabetes or T2D. Currently, pharmacological intervention for older adults with 
prediabetes is not widely recommended although has been done in clinical trials with resultant reduction in 
diabetes onset . Further, older adults with diabetes who are otherwise healthy may not have medical 
management (i.e., drug therapy) added until glycemic goals are unmet (HbA1c >7.0-7.5%), which may have 
detrimental, lasting effects on aging muscle. If positive, our results would support the use of GLP1 receptor 
agonists in older adults with prediabetes or in well controlled diabetes earlier in the disease course to halt 
the progression of physical function decline and improve biomarkers of aging. Therefore, this knowledge will 
contribute to future studies in this area that will allow for geroscience-guided therapy for prediabetes and 
T2D in older adults to extend healthspan.  
To minimize the risk of weight loss, we will enroll participants who meet the indication for GLP1 receptor 
agonist therapy for weight management in the presence of at least one comorbid condition which for this 
study will be prediabetes or diabetes (BMI ≥ 27.0, HgbA1c ≥ 5.7). We will have an upper limit for HgbA1c of 
7.5% because at this time most clinicians would start or intensify medical therapy. We will have a BMI upper 
limit of 40.0 for ability to use DXA.    
 
 
5. Study Design 
5.1. Number of Groups/Arms 
2 
Group name(s) 
(1) Medication and lifestyle  (2) Lifestyle alone 
5.2. Overall Design 
Select all applicable   
☒ 
 Randomization   
☐ 
Cluster Randomized 
☐ 
Group-Sequential 
☐ 
Adaptive Design 
☐ 
Parallel Design 
☐ 
Placebo-Controlled 
☐ 
Superiority 
☐ 
Equivalence 
☐ 
Non-inferiority 
Device 
☐ 
Pilot 
☐ 
Pivotal 
☐ 
Post-Approval 
Drug/Biologic 
☒ 
Phase 1 
☐ 
Phase 1/2 
☐ 
Phase 2 
☐ 
Phase 2/3 
☐ 
Phase 3 
☐ 
Phase 4 
☒ 
Dose escalation  
If yes, details → 
0.25mg weekly for 4 weeks, then 0.5mg weekly for 4 weeks, then 1mg weekly for 12 
weeks. If unable to tolerate a higher dose then will adjust titration schedule.  
☐ 
Dose ranging 
If yes, details → 
 
☐ 
Sub-studies 
If yes, details → 
 
5.3. Other Design Details: This will be a 20 week open label, randomized control trial. The study will start after approval from UT 
Health San Antonio IRB department. Subjects will be consented and then screened for eligibly before randomization into either 
the lifestyle or lifestyle plus study drug arm. All study visits will be performed at Barshop Clinical Research Unit.  
 
 
 
6.  Study Population 
 
6.1.  Study Population(s) 
Label/Name 
 
 
 
 
To add more populations – select a row, copy & 
paste 
6.2.  Identify the criteria for inclusion 
The criteria that every potential participant must 
satisfy, to qualify for study entry.  
 
All individuals in this study population must meet 
all of the inclusion criteria in order to be eligible 
to participate in the study  
6.3.  Identify the criteria for exclusion 
The characteristics that make an individual ineligible 
for study participation.   
 
All individuals in this study population meeting 
any of the exclusion criteria at baseline will be 
excluded from study participation. 
Overweight/obese 
community dwelling older 
1) Men and post-menopausal 
women 
2) Age ≥ 65 years 
1) Impaired renal function (GFR ≤ 
29) 
2) Hematocrit ≤ 33  


 
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adults with prediabetes or 
T2D.  
3) All ethnic groups 
4) BMI ≥ 27.0 kg/m2 
5) HbA1c 5.7-7.5%, fasting glucose 
≥ 100,  
7) Community – dwelling  
8) At PI discretion, participant is 
willing/able to comply with the 
protocol requirements  
3) Thyroid-stimulating hormone≥ 7 
with an abnormal free T4 
4) Immunodeficiency 
5) Use of medications known to 
affect glucose homeostasis besides 
metformin (metformin is allowed) 
6) History of cardiovascular events 
7) Poorly controlled blood pressure 
(systolic blood pressure >170, 
diastolic blood pressure >95) 
8) Active inflammatory, autoimmune, 
infectious, hepatic, gastrointestinal, 
malignant, or uncontrolled 
psychiatric disease  
9) stable body weight (<5% change 
during the 3 months prior to 
screening) 
10) personal or family history of 
medullary thyroid cancer (MTC) 
11) personal or family history of 
Multiple Endocrine Neoplasia 
syndrome type 2 (MEN 2) 
12) previous history of pancreatitis, 
13) ECG with QTc prolongation (QTc 
>470 ms in men or >480 ms in 
women) or evidence of ischemic 
changes  
14) Diabetic Retinopathy 
15) Allergy to semaglutide or any of 
the ingredients in the drug 
formulation 
16) Type 1 Diabetes  
17) BMI ≥ 40 kg/m2 
18) Current tobacco or illicit drug use 
6.4.  
Will screen failures be allowed to 
re-screen at a later date? 
☐ 
No 
☒ 
Yes           If yes, describe criteria below ↓ 
Will be able to be rescreened after 12 weeks  
 
 
7.  Study Intervention(s) being tested or evaluated 
This can include prevention, diagnostic or therapeutic interventions (e.g., drug or device) or educational, health services or basic science interventions (e.g., 
educational program, health care delivery model,  or examining basic physiology)  
 
Semaglutide (Ozempic )  
 
8.  Protocol-Directed procedures, items, services or tests 
List all procedures directed by the study plan - including items or services provided as part of routine or conventional care and those needed to diagnosis or treat 
research related complications.    
Important Note – The protocol directed procedures listed must match those in the Schedule of Activities (attachment) 
8.1. Drugs (trade and generic, dosage, route of administration)     
Control group-lifestyle alone group: Subjects will meet with a dietician throughout the study to discuss 
lifestyle counseling based on recommendation in the diabetes prevention program.  


 
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Intervention group- Semaglutide+ lifestyle : Ozempic , starting at 0.25mg once a week for 4 weeks then 
0.5mg once weekly for 4 weeks followed by 1.0mg once a week, subcutaneously as tolerated. Additionally, 
they will meet with a dietician through the study to discuss lifestyle counseling based on recommendation in 
the diabetes prevention program. 
 
 
 
 
 
8.2. Devices 
 
 
8.3. Biologics 
 
 
8.4. Laboratory Tests  
Clinical labs include CBC, lipid panel, CMP, TSH, PT/INR, PTT, and HbA1c will be done to determine 
eligibility and follow the effect of treatment. 
 
8.5. Imaging Procedures  
 
 
8.6. Other Research Procedures (e.g., other safety and efficacy assessments.)  
-ECG: ECG will be performed to examine for  QTc prolongation or other cardiac issues contraindicated for 
exercise 
-Vitals and anthropometric measurements:  Weight will be measured at all visits to track BMI, heart rate, and 
blood pressure 
-Functional assessments of SPPB, 6 minute walking distance, and grip strength will be done at baseline and 
at end of study to determine the effect of the intervention. 
-Questionnaires of SF-12 (quality of life) and CNAQ (appetite assessment) will be done at baseline and at 
end of study determine the effect of the intervention.  
-DXA: body composition will be determined by DXA at baseline and end of study to determine the effect of 
the intervention  
-Assays of cellular senescence and senescence-associated secretory phenotype (SASP) in muscle, adipose 
and blood will be conducted in the Barshop Institute, including   galactosidase staining, PCR (IL-6, TNFα, 
p16, p21, TLR4, and MCP1), and immunoassays (CRP, ADAMTS13, CCL3, CCL4, CCL5, CCL17, CCL22, 
FAS, GDF15, GDNF, ICAM1, IL15, IL6, IL7, IL8, MMP2, MMP9, OPN, PAI1, SOST, TNFR1, TNFα, and 
VEGFA). These will be done at the beginning and end of study to determine the effect of study intervention.  
8.7  Attach a Schedule of Activities (SOA) Excel File  [Download the Template here: Schedule of Activities] 
Check to indicate that the  
SOA Excel File is attached  → X 
☐ 
 
 
9. 
Preparation/Handling/ Storage/Accountability of Investigational Drug, Biologic, or Device 
N/A  - This study does not include any investigational products (e.g. drugs, devices or biologics) 
 
N/A  - An Investigator Brochure is attached 
 
X N/A  - A Drug/Device Manual is attached- The FDA prescribing insert for both Wegovy and Ozempic which are the trade 
names for semaglutide.  
☐ 
☐ 
☐ 


 
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9.1.  Acquisition and accountability 
State how the study intervention and control product will be provided to the investigator. Describe plans about how and by whom the study intervention will be 
distributed, including participation of a drug repository or pharmacy, and plans for disposal of expired or return of unused product. 
Semaglutide will be provided by the pharmacy to Barshop staff. Barshop staff will then dispense medication 
and log in appropriate visits. Unused medication will be returned to pharmacy for disposal.  
9.2. Formulation, Appearance, Packaging, and Labeling 
Describe the formulation, appearance, packaging, and labeling of the study intervention and control product, as supplied.  Information in this section can usually 
be obtained from the IB or the package insert, or device labeling. This section should include the name of the manufacturer of the study intervention and control 
product. 
 
SEMAGLUTIDE DOSAGE FORMS AND STRENGTHS:  
 Injection: 2 mg/1.5 mL (1.34 mg/mL) of semaglutide as a clear, colorless solution available in: 
- Pre-filled, disposable, single-patient-use pen that delivers 0.25 mg (for treatment initiation) or 0.5 mg (for maintenance 
treatment) per injection.  
-Pre-filled, disposable, single-patient-use pen that delivers 1 mg (for maintenance treatment) per injection. 
 
We will only be using Ozempic in this study. Since Ozempic and Wegovy are the same active ingredient used at different 
doses (Wegovy starts at 0.25mg once a week and increases up to 2.4mg once a week), we have add the indications for 
Wegovy.  
 
INDICATIONS AND USAGE 
OZEMPIC (semaglutide) is a glucagon-like peptide 1 (GLP-1) receptor agonist 
indicated as: 
• an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. 
• to reduce the risk of major adverse cardiovascular events in adults with type 2 diabetes mellitus and established 
cardiovascular 
disease . 
 
WEGOVY (semaglutide) is a glucagon-like peptide-1 (GLP-1) receptor agonist indicated as an adjunct to a reduced calorie 
diet and increased physical 
activity for chronic weight management in adult patients with an initial body mass index (BMI) of 
• 30 kg/m2 or greater (obesity) or 
• 27 kg/m2 or greater (overweight) in the presence of at least one weight-related comorbid condition (e.g., hypertension, type 
2 diabetes mellitus, or dyslipidemia).  
 
Manufactured by: Novo Nordisk A/S DK-2880 Bagsvaerd Denmark 
9.3.  Product Storage and Stability 
Describe storage and stability requirements (e.g., protection from light, temperature, humidity) for the study intervention and control product.  For studies in which 
multi-dose vials are utilized, provide additional information regarding stability and expiration time after initial use (e.g., the seal is broken). 
We will be providing participants Ozempic in the intervention arm.  
 
Prior to first use, OZEMPIC should be stored in a refrigerator between 36ºF to 46ºF (2ºC to 8ºC). Do not store in the 
freezer or directly adjacent to the refrigerator cooling element. Do not freeze OZEMPIC and do not use OZEMPIC if it 
has been frozen. Can be used until expiration on pen.  
  
After first use of the OZEMPIC pen, the pen can be stored for 56 days at controlled room temperature (59°F to 86°F; 
15°C to 30°C) or in a refrigerator (36°F to 46°F; 2°C to 8°C). Do not freeze. Keep the pen cap on when not in use. 
OZEMPIC should be protected from excessive heat and sunlight.   
 
9.4.  Preparation 
Describe the preparation of the study intervention and control product, including any preparation required by study staff and/or study participants.  Include 
thawing, diluting, mixing, and reconstitution/preparation instructions in this section. For devices, include any relevant assembly or use instructions. 
NA –Medication will be obtained from MedPlus pharmacy (may change based on cost of medication). The medication 
will be labeled “for investigational use only” in addition to the usual labeling of medication, dose and instructions.  
9.5. Risks and Benefits 
Risks 
Risk of Thyroid C-cell Tumors  


 
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Semaglutide causes thyroid C-cell tumors in rodents and that the human relevance of this finding has not been 
determined. Counsel patients to report symptoms of thyroid tumors (e.g., a lump in the neck, hoarseness, dysphagia, 
or dyspnea) to their physician [see Boxed Warning and Warnings and Precautions (5.1)]. 
Pancreatitis  
There is a potential risk for pancreatitis. Instruct will be given to patients to discontinue OZEMPIC promptly and contact 
the study team if pancreatitis is suspected (severe abdominal pain that may radiate to the back, and which may or may 
not be accompanied by vomiting). 
Diabetic Retinopathy Complications  
Inform patients to contact the study team immediately if changes in vision are experienced during treatment with 
OZEMPIC  
Never Share an OZEMPIC Pen Between Patients.  
Advise patients that they must never share an OZEMPIC pen with another person, even if the needle is changed, 
because doing so carries a risk for transmission of blood-borne. 
Dehydration and Renal Failure  
There are potential risk of dehydration due to gastrointestinal adverse reactions and precautions should be taken to 
avoid fluid depletion. There is a potential risk for worsening renal function and participants will be informed about the 
associated signs and symptoms of renal impairment, as well as the possibility of dialysis as a medical intervention if 
renal failure occurs.  
Hypersensitivity Reactions  
Participants will be informed to stop taking OZEMPIC and seek medical advice promptly if symptoms of hypersensitivity 
reactions occur. 
 
Most common side effects of semaglutide administration are nausea, vomiting, diarrhea, abdominal pain and 
constipation which usually decrease over time in the majority of patients. 
 
Possible Benefits 
• 
Improved glycemic control in type 2 diabetic participants 
• 
Beneficial weight loss leading to decreased BMI 
• 
Possible improvement of pro-inflammatory milieu 
• 
If positive, study results would support the use of GLP1 receptor agonists in older adults with prediabetes or in 
well controlled diabetes earlier in the disease course to halt the progression of physical function decline and 
improve biomarkers of aging. Therefore, this knowledge will contribute to future studies in this area that will 
allow for geroscience-guided therapy for prediabetes and T2D in older adults to extend healthspan. 
 
 
10.  Study Intervention Additional Details 
10.1.  Measures to Minimize Bias: Randomization and Blinding 
This section should contain a description of randomization and blinding procedures (if applicable to the 
study design).  It should include a description or a table that describes how study participants will be 
assigned to study groups, without being so specific that blinding or randomization might be compromised.  
Plans for the maintenance of trial randomization codes and appropriate blinding for the study should be 
discussed. The timing and procedures for planned and unplanned breaking of randomization codes should be 
included.  Include a statement regarding when unblinding may occur and who may unblind. Provide the 
criteria for breaking the study blind or participant code.  Discuss the circumstances in which the blind would 
be broken for an individual or for all participants (e.g., for serious adverse evets (SAEs)). Indicate to whom 
the intentional and unintentional breaking of the blind should be reported. 
The study is unblinded. Participants (N=20) will be randomized into two groups using a randomization table 
to receive either  (1) semaglutide plus standard lifestyle recommendation or (2) standard lifestyle 
recommendations alone.  
10.2.  Study Intervention Compliance 
Define how adherence to the protocol (e.g., administration of study intervention, use of device,) will be 
assessed, and verified (if applicable, e.g., plasma assays, electronic monitoring devices, daily diaries). 


 
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Participants will have four visits while on study medication to discuss whether they remain eligible and if 
there are any adverse events to report and to verify adherence to protocol. They will be asked to bring in 
their medication to study visits if randomized to the study drug arm to determine adherence.  
 
10.3.  Permitted Concomitant Therapy 
This section should be consistent with the medication restrictions in the inclusion/exclusion criteria 
previously listed.  Describe how allowed concomitant therapy might affect the outcome (e.g., drug-drug 
interaction, direct effects on the study endpoints). 
Use of medications known to affect glucose homeostasis besides metformin (metformin is allowed) is a part 
of exclusion criteria. Other medications will be allowed.  
10.4.  
 
Rescue Medicine 
List all medications, treatments, and/or procedures that may be provided during the study for 
“rescue therapy” and relevant instructions. 
☒ 
: N/A, no rescue medicine 
 
 
 
 
11.  Study Intervention Discontinuation  
11.1.  Discontinuation of Study Intervention 
Describe the criteria for discontinuing the study intervention (e.g., halting rules), including any monitoring test(s) and associated clinical decision point(s). Include 
reasons for temporary discontinuation of the study intervention (e.g., type and quantity of adverse events), clearly stating the length of time, if applicable, and 
describe the data to be collected at the time of study intervention discontinuation and approaches for restarting administration of or re-challenging with study 
intervention.   
Study medication will be discontinued in the event of a severe allergic reaction or development of an episode of pancreatitis.  
If minor GI (nausea, abdominal pain, vomiting, etc ) side effects occur, then the study medication titration will be modified based 
on symptoms and severity of these anticipated side effects.  
11.2.  Continued Follow-up Discontinuation of Study Intervention 
Describe efforts that will be made to continue follow-up of participants who discontinue the study intervention, but remain in the study for follow-up, especially for 
safety and efficacy study endpoints (if applicable).  Reasonable efforts must be made to undertake protocol-specified safety follow-up procedures to capture 
adverse events (AE), serious adverse events (SAE), and unanticipated problems involving risks to subjects or others (UPIRSOs). 
If participants discontinue study medication, then we will follow up with participants to determine resolution of symptoms and 
relationship with medication. 
 
 
12.  Statistical Considerations 
12.1. Statistical Hypotheses   
State the formal and testable null and alternative hypotheses for primary and key secondary endpoints, specifying the type of comparison (e.g., superiority, 
equivalence or non-inferiority, dose response) and time period for which each endpoint will be analyzed. 
We hypothesize that semaglutide will improve physical function (SPPB, handgrip strength, walking speed) and body 
composition (BMI, lean body mass to fat mass ratio) in those with prediabetes and well controlled diabetes. It is 
expected that the pleiotropic effects of GLP1 receptor agonists will also result in improvement of aging biomarkers 
including cellular senescence and inflammation in muscle and adipose tissue.   
12.2.  Sample Size Determination 
Include number of participants to recruit, screen, and enroll to have adequate power to test the key hypotheses for the study.  Provide all information needed to 
validate your calculations and judge the feasibility of enrolling and following the necessary number of participants. 
The effect of GLP1 receptor agonists on aging-related biomarkers and physical function in is not known.  For this pilot 
study, we will screen up to 100 potentially eligible participants to achieve a target of 20 completers. More candidates 
will be screened if attrition (est. 20%) requires it. The data generated through this study will guide sample size and 
power calculations for future studies. 


 
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12.3.  Populations for Analyses 
Clearly identify and describe the analysis datasets (e.g., which participants will be included in each). 
Population for analyses will be divided in the two arms (1) medication and lifestyle and (2) lifestyle alone 
12.4.  Statistical Analyses    
Include analysis of primary efficacy endpoints, secondary endpoints, safety analyses, and any planned interim analyses 
Experimental results will be expressed as means ± SE.  Comparisons of means between all the groups will 
be done by ANOVA for repeated measures.  Associations, within a group, between aging-related biomarkers 
vs. healthspan outcomes will be determined by Pearson’s correlation. For tests of correlation coefficients 
between groups, we will use the Fisher’s Z transformation.  We will also determine the relationship between 
aging-related biomarkers vs healthspan outcomes, by using multiple regression analysis.