Effects of Tirzepatide on Muscle and Vascular Health in Obese Older Adults

NCT06811324 | Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: STUDY00001208
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

Obesity and type 2 diabetes mellitus (T2DM) represent major public health concerns in the aging community. Tirzepatide, a novel dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptor agonist recently approved for the treatment of T2DM and obesity has been shown to be effective at reducing weight, improving markers of T2DM control, and improving cardiovascular health. Utilization of tirzepatide among older adults has been on the rise since FDA approval was issued, however the effects of tirzepatide use on functional outcomes in older adults with obesity are not well established. Recent studies show that weight loss caused by tirzepatide may be driven by substantial loss of lean muscle mass, which may contribute to weakness and frailty, particularly among older adults. The proposed pilot study aims to evaluate how treatment with tirzepatide for 6 months affects muscle mass and function among older adults, and if changes in muscle mass are linked to changes in functional status over the same time period.

Conditions

Obesity Prevention; Sarcopenia in Elderly; Cardiovascular Function; GLP - 1; Weight Loss

Keywords

Tirzepatide; GLP-1; Obesity; Sarcopenia; Cardiovascular Function

Outcome Measures

Primary Outcomes (3)

• Appendicular lean muscle mass

  Appendicular lean muscle mass assessed at baseline and at 6-month follow-up by dual-energy X-ray absorptiometry (DEXA)

  6 months

• Muscle Strength

  Muscle strength assessed by isokinetic and isometric testing using Biodex dynamometry at baseline and at 6-month follow-up.

  6 months

• Lower Extremity Functional Capacity

  Functional capacity will be measured using the 6-minute walk test (6MWT) at baseline and 6-month follow up visit.

  6 months

Study Arms (1)

Tirzepatide

EXPERIMENTAL

Tirzepatide self-administered once weekly by subcutaneous injection

Drug: Tirzepatide

Interventions

Tirzepatide DRUG

Once weekly tirzepatide starting at 2.5 mg/weekly, with dose escalation monthly by 2.5 mg to a target dose of 10 mg/weekly or maximum tolerated

Also known as: Zepbound, LY3298176

Tirzepatide

Eligibility Criteria

• Age: 50 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Men and postmenopausal women aged 50 years or older.
• Body Mass Index (BMI) ≥30 kg/m².
• Untreated HbA1c \<6.5% at baseline.
• Willingness and ability to comply with all study procedures, including fasting requirements for certain visits.
• Able to provide informed consent and participate in all study assessments.

You may not qualify if:

• Active diagnosis of type 2 diabetes mellitus (T2DM), defined by active use of glucose-lowering medications or hemoglobin A1c ≥ 6.5%.
• Body Mass Index (BMI) ≥ 40 kg/m².
• Moderate to severe gastroesophageal reflux disease based on patient history.
• Inability to comply with the treatment protocol or to understand the consent form.
• Chronic Kidney Disease (CKD) Stage 4.
• Aspartate aminotransferase (AST) \> 33 U/L or alanine aminotransferase (ALT) \> 36 U/L.
• Active pregnancy.
• Personal or family history of medullary thyroid carcinoma.
• Personal or family history of multiple endocrine neoplasia type 2 syndrome.
• Personal history of gastroparesis.
• Personal history of diabetic retinopathy.
• Known serious hypersensitivity, including anaphylaxis and angioedema, to Tirzepatide or any of its excipients.
• Known serious hypersensitivity, including anaphylaxis and angioedema, to any GLP-1 receptor agonist class of therapies.
• Concomitant treatment with GLP-1 receptor agonist therapy

Sponsors & Collaborators

• The University of Texas Health Science Center at San Antonio: lead

Study Sites (1)

University of Texas Health Science Center at San Antonio

San Antonio, Texas, 78229, United States

RECRUITING

Related Publications (13)

• Marx N, Husain M, Lehrke M, Verma S, Sattar N. GLP-1 Receptor Agonists for the Reduction of Atherosclerotic Cardiovascular Risk in Patients With Type 2 Diabetes. Circulation. 2022 Dec 13;146(24):1882-1894. doi: 10.1161/CIRCULATIONAHA.122.059595. Epub 2022 Dec 12.

  PMID: 36508493 BACKGROUND

• Clark RV, Walker AC, O'Connor-Semmes RL, Leonard MS, Miller RR, Stimpson SA, Turner SM, Ravussin E, Cefalu WT, Hellerstein MK, Evans WJ. Total body skeletal muscle mass: estimation by creatine (methyl-d3) dilution in humans. J Appl Physiol (1985). 2014 Jun 15;116(12):1605-13. doi: 10.1152/japplphysiol.00045.2014. Epub 2014 Apr 24.

  PMID: 24764133 BACKGROUND

• Colleluori G, Villareal DT. Aging, obesity, sarcopenia and the effect of diet and exercise intervention. Exp Gerontol. 2021 Nov;155:111561. doi: 10.1016/j.exger.2021.111561. Epub 2021 Sep 23.

  PMID: 34562568 BACKGROUND

• Wilkinson DJ, Piasecki M, Atherton PJ. The age-related loss of skeletal muscle mass and function: Measurement and physiology of muscle fibre atrophy and muscle fibre loss in humans. Ageing Res Rev. 2018 Nov;47:123-132. doi: 10.1016/j.arr.2018.07.005. Epub 2018 Jul 23.

  PMID: 30048806 BACKGROUND

• Wadden TA, Chao AM, Machineni S, Kushner R, Ard J, Srivastava G, Halpern B, Zhang S, Chen J, Bunck MC, Ahmad NN, Forrester T. Tirzepatide after intensive lifestyle intervention in adults with overweight or obesity: the SURMOUNT-3 phase 3 trial. Nat Med. 2023 Nov;29(11):2909-2918. doi: 10.1038/s41591-023-02597-w. Epub 2023 Oct 15.

  PMID: 37840095 BACKGROUND

• Conte C, Hall KD, Klein S. Is Weight Loss-Induced Muscle Mass Loss Clinically Relevant? JAMA. 2024 Jul 2;332(1):9-10. doi: 10.1001/jama.2024.6586.

  PMID: 38829659 BACKGROUND

• Frias JP, Davies MJ, Rosenstock J, Perez Manghi FC, Fernandez Lando L, Bergman BK, Liu B, Cui X, Brown K; SURPASS-2 Investigators. Tirzepatide versus Semaglutide Once Weekly in Patients with Type 2 Diabetes. N Engl J Med. 2021 Aug 5;385(6):503-515. doi: 10.1056/NEJMoa2107519. Epub 2021 Jun 25.

  PMID: 34170647 BACKGROUND

• Kaneko S. Tirzepatide: A Novel, Once-weekly Dual GIP and GLP-1 Receptor Agonist for the Treatment of Type 2 Diabetes. touchREV Endocrinol. 2022 Jun;18(1):10-19. doi: 10.17925/EE.2022.18.1.10. Epub 2022 Jun 16.

  PMID: 35949358 BACKGROUND

• Koyama AK, McKeever Bullard K, Xu F, Onufrak S, Jackson SL, Saelee R, Miyamoto Y, Pavkov ME. Prevalence of Cardiometabolic Diseases Among Racial and Ethnic Subgroups in Adults - Behavioral Risk Factor Surveillance System, United States, 2013-2021. MMWR Morb Mortal Wkly Rep. 2024 Jan 25;73(3):51-56. doi: 10.15585/mmwr.mm7303a1.

  PMID: 38271277 BACKGROUND

• Prado CM, Phillips SM, Gonzalez MC, Heymsfield SB. Muscle matters: the effects of medically induced weight loss on skeletal muscle. Lancet Diabetes Endocrinol. 2024 Nov;12(11):785-787. doi: 10.1016/S2213-8587(24)00272-9. Epub 2024 Sep 9. No abstract available.

  PMID: 39265590 BACKGROUND

• Neeland IJ, Linge J, Birkenfeld AL. Changes in lean body mass with glucagon-like peptide-1-based therapies and mitigation strategies. Diabetes Obes Metab. 2024 Sep;26 Suppl 4:16-27. doi: 10.1111/dom.15728. Epub 2024 Jun 27.

  PMID: 38937282 BACKGROUND

• Larsson L, Degens H, Li M, Salviati L, Lee YI, Thompson W, Kirkland JL, Sandri M. Sarcopenia: Aging-Related Loss of Muscle Mass and Function. Physiol Rev. 2019 Jan 1;99(1):427-511. doi: 10.1152/physrev.00061.2017.

  PMID: 30427277 BACKGROUND

• Eberly LA, Yang L, Essien UR, Eneanya ND, Julien HM, Luo J, Nathan AS, Khatana SAM, Dayoub EJ, Fanaroff AC, Giri J, Groeneveld PW, Adusumalli S. Racial, Ethnic, and Socioeconomic Inequities in Glucagon-Like Peptide-1 Receptor Agonist Use Among Patients With Diabetes in the US. JAMA Health Forum. 2021 Dec 17;2(12):e214182. doi: 10.1001/jamahealthforum.2021.4182. eCollection 2021 Dec.

  PMID: 35977298 BACKGROUND

MeSH Terms

Conditions

Weight Loss; Obesity; Sarcopenia

Interventions

Tirzepatide

Condition Hierarchy (Ancestors)

Body Weight Changes; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Overweight; Overnutrition; Nutrition Disorders; Nutritional and Metabolic Diseases; Muscular Atrophy; Neuromuscular Manifestations; Neurologic Manifestations; Nervous System Diseases; Atrophy; Pathological Conditions, Anatomical

Intervention Hierarchy (Ancestors)

Glucagon-Like Peptide-1 Receptor; Glucagon-Like Peptide Receptors; Receptors, G-Protein-Coupled; Receptors, Cell Surface; Membrane Proteins; Proteins; Amino Acids, Peptides, and Proteins; Receptors, Gastrointestinal Hormone; Receptors, Peptide

Study Officials

• Shreya Rao, MD, MPH

  The University of Texas Health Science Center at San Antonio

  PRINCIPAL INVESTIGATOR

• Elena Volpi, MD, PhD

  The University of Texas Health Science Center at San Antonio

  PRINCIPAL INVESTIGATOR

• Tiffany Cortes, MD

  The University of Texas Health Science Center at San Antonio

  STUDY DIRECTOR

Central Study Contacts

Suha Soni

CONTACT

(210)450-3333; BCRU@uthscsa.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor

Study Record Dates

• First Submitted: January 31, 2025
• First Posted: February 6, 2025
• Study Start: April 1, 2026
• Primary Completion (Estimated): April 1, 2027
• Study Completion (Estimated): June 1, 2027
• Last Updated: April 15, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Data will be available beginning 1 year after the end of the trial and publication of the primary outcomes, and will be available for 24 months.
• Access Criteria: Data will be available to researchers who provide a methodologically sound proposals. Proposals should be directed to the principal investigators. To gain access, data requestors will need to sign a data access agreement.

Locations

US (1)