GLP-1R Actions on Muscle and the Skeleton

What Was Tested

The trial (phase 4) is built around Tirzepatide.

The GRAMS study objectives are to assess the musculoskeletal changes that occur after weight loss using GLP-1 based therapy.

A lifestyle intervention with diet and exercise is included to assess any mitigating effects are provided, versus a control group with regular exercise and diet.

It had two arms (groups): Treatment/intervention group (experimental) and Control/Placebo (placebo comparator).

Treatment with Tirzepatide for 5 months and lifestyle toolkit.

Treatment with Tirzepatide for 5 months with regular diet and exercise.

The registry classes the interventions as behavioral and drug.

More on the Plan

Obesity and type 2 diabetes remain at epidemic proportions in their country particularly in vulnerable populations such as elderly, and minority patients.

The impact of losing weight on the musculoskeletal system has garnered recent attention in the lay press.

Reported high-impact studies have reported excessive loss of skeletal muscle using GLP-1 RAs.

This preliminary data is based on using a surrogate marker (fat-free mass) determined by dual energy x-ray absorptiometry (DXA).

Who Took Part

50 planned participants were the target.

It was open to people of any sex aged from 18 years up to 50 years.

Healthy volunteers were not accepted; participants needed the condition being studied.

Examples of who could join: Subjects will have a BMI between 30kg/m2. Be between 18 and 50 years of age (inclusive). Non-Hispanic Black males and females will be enrolled at PBRC. Female subjects will be premenopausal. Females have had their last menstrual period less than 60 days before screening.

The full record lists 9 inclusion and 18 exclusion criteria; among the exclusions: menopausal females; subjects having contraindications to tirzepatide in the package insert; subjects with a history of malignancy other than non-melanoma skin cancer.

How the Study Was Run

It was run as a randomized, parallel-group and open-label study.

Because people in this Tirzepatide study were split into groups at random, differences between the groups are less likely to reflect who happened to join each one.

Groups ran in parallel: each of the participants stayed in one arm throughout.

Nothing was hidden in this open-label Tirzepatide study: the participants and staff both knew the treatment.

It started in 2025-10-09 with completion listed for 2027-02-01.

It ran at 2 sites in United States (2).

Its stated primary purpose is treatment.

What Was Measured

The main thing measured (primary outcome): Changes in fat free mass (FFM) using DXA imaging. FFM equals all body composition that is not fat mass. This includes bone, skeletal muscle, organs, water and all connective tissues. The unit of measurement is in kilograms (kg) at baseline, 3 and 6 mo (time frame: Baseline and time 3, and 6 months).

It also tracked 6 secondary outcomes, for example MRI (thigh) without contrast, Osteocalcin, Irisin, Procollagen 1 N-terminal peptide (P1NP), C-Terminal Telopeptide of type I collagen (CTX-1) and Insulin-like Growth Factor 1 (IGF-1).

What This Means in Plain Language

Put simply, this is a phase 4, randomized trial of Tirzepatide in 50 people.

It is still recruiting; no results are posted to the registry yet, so nothing here describes outcomes.

More context: the Tirzepatide compound page, all human trials.