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

Официальное название

The Effects of Tirzepatide Use on Muscle and Vascular Function Among Obese Older Adults

Обзор

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.

Подробное описание

This study is a pilot, single-arm, open-label clinical trial to evaluate the effects of Tirzepatide on muscle mass, strength, and vascular health among older adults with obesity. This study is set in South Texas, where rates of obesity and related health issues, including type 2 diabetes and cardiovascular conditions, exceed national averages and where aging-related diseases are on the rise. Tirzepatide is a new FDA approved medication that promotes weight loss and improves health by targeting specific pathways in the body. While it has been shown to be effective in managing weight and blood sugar levels, there is less information about the kind of weight loss it induces, and how weight loss impacts measures of muscle mass, strength and mobility. This is especially concerning for older adults, as losing muscle mass can lead to weakness, falls, and disability.

Вмешательства

• Препарат Tirzepatide
  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

Первичные конечные точки

• Appendicular lean muscle mass [Срок оценки: 6 months]
• Muscle Strength [Срок оценки: 6 months]
• Lower Extremity Functional Capacity [Срок оценки: 6 months]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Другое

Центры проведения

США · 1 центр

• University of Texas Health Science Center at San Antonio — San Antonio

Публикации

• 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
• 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
• 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
• 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
• 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
• 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
• 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
• 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

Идентификаторы

NCT: NCT06811324 · STUDY00001208

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗