Overview

This pilot clinical study aims to investigate the potential effects of tirzepatide on biological aging in older adults. In this novel study, 90 adults aged 55-70 years with an indication for tirzepatide weight-loss therapy will be randomized to receive either tirzepatide 2.5 mg subcutaneously (SC) weekly or no drug for 24 weeks, followed by 12 weeks off the drug. Since tirzepatide is already recognized as a highly effective weight-loss agent in this population, the primary focus will not be on measuring weight loss. Instead, the study will document the effects of tirzepatide on markers of aging, physical function, and overall health.

Eligibility

Inclusion Criteria:

1. Age 55-70 years
2. BMI ≥ 30 kg/m² or ≥ 27 kg/m² if also with ≥ 1 weight-related comorbidity
3. If taking anti-inflammatory or blood-pressure-/lipid-/glucose-lowering medications, no change in dose for ≥12 weeks prior to entry and no plans to dose escalate for the study duration
4. Willing and able to provide written informed consent and undergo all required study procedures

Exclusion Criteria:

1. BMI \>35 kg/m²
2. Uncontrolled or end-stage, comorbid, cardiometabolic disease, in the opinion of the site investigator
3. Significant neurocognitive impairment, in the opinion of the site investigator
4. Current or planned use of medications for the treatment of obesity, or medications likely to cause significant changes in weight, during the study period (see prohibited medications, section 6.0)
5. Use of insulin
6. Plans to newly engage in formal, intensive physical activity or diet (such as ketogenic or very low carbohydrate) programs during the study period
7. Active eating disorder
8. Use of human growth hormone, tesamorelin, supraphysiologic testosterone or estradiol (stable doses for contraception, hypogonadism or other indications for exogenous sex steroid replacement therapy permitted) or anabolic steroids \<12 W prior to entry, unless on a stable dose for \>24 W prior to entry, or plans to start any of these medications while on study
9. Active, severe delayed gastric emptying
10. Prior bariatric surgery or major gastric surgery or plans for weight reduction surgery while on study
11. Known diabetic retinopathy
12. Personal or first-degree relative history of medullary thyroid carcinoma or multiple endocrine neoplasia type 2
13. Untreated, poorly controlled or previously undiagnosed thyroid disease
14. History of chronic pancreatitis
15. History of suicidal attempts or active suicidal ideation, in the opinion of the site investigator
16. Known allergy/sensitivity to GLP-1RA or GIPRA
17. Use or planned use of any immunomodulatory therapy or investigational therapy during the study period or use of an investigational therapy within 30 days of entry
18. Any other medical condition that, in the opinion of the investigator, would place the subject at increased risk for participation.
19. Pregnancy, nursing or plans for either during the study period