Investigating the Impact of GLP-1 RA Therapy on Osteosarcopenia in Older Female Adults With Diabetes (GLOW)

The goal of this study is to learn how GLP-1 receptor agonist therapy affects muscle and bone health in older females over age 65 with type 2 diabetes.

The main question it aims to answer is whether or not 6 months of GLP-1 RA therapy affects muscle strength.

Participants will:

• Receive GLP-1 RA therapy as part of their routine clinical care
• Complete muscle strength assessments (hand grip strength, Timed Up and Go test)
• Provide blood samples for bone turnover markers
• Undergo bone mineral density testing

Study Overview

• Status: Not yet recruiting
• Conditions: Diabetes Mellitus, Type 2
• Intervention / Treatment: Drug: Semaglutide

Detailed Description

Older females with type 2 diabetes experience a disproportionately high burden of osteosarcopenia, a condition defined by the coexistence of low muscle mass, reduced muscle strength, and decreased bone mineral density. Osteosarcopenia is associated with increased risks of falls, fractures, functional decline, hospitalization, and loss of independence. Diabetes contributes to these risks through multiple mechanisms, including impaired bone microarchitecture, reduced muscle quality, neuropathy-related balance disturbances, and chronic inflammation. These effects are amplified in older women, who already experience age-related declines in muscle and bone health following menopause.

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs), including semaglutide, are widely used for glycemic management and weight reduction in type 2 diabetes. While these medications provide substantial metabolic benefits, clinical studies have reported that weight loss associated with GLP-1 RA therapy may include reductions in lean body mass. The implications of these changes for muscle strength, bone turnover, and bone mineral density remain unclear, particularly in older females with type 2 diabetes who may be more vulnerable to muscle and bone loss. Existing data on GLP-1 RAs and fracture risk are limited and inconsistent, and most prior studies have evaluated older, less potent agents with minimal weight-loss effects.

This prospective observational study is designed to characterize changes in muscle and bone health during 6 months of GLP-1 RA therapy in older females with type 2 diabetes who are receiving treatment as part of routine clinical care. The study will enroll 20 women over the age of 65. Participants will undergo standardized assessments of muscle strength, bone turnover markers, and bone mineral density at baseline and follow-up. Muscle strength will be evaluated using validated functional measures, and bone health will be assessed through laboratory markers of bone remodeling and imaging-based measures of bone density.

The study does not alter clinical treatment decisions; GLP-1 RA therapy is prescribed independently by participants' healthcare providers based on FDA-approved indications. Study procedures focus on evaluating physiological changes associated with treatment in a population at elevated risk for osteosarcopenia. Data collected will help clarify whether GLP-1 RA therapy influences muscle strength, bone turnover, or bone mineral density in older females with type 2 diabetes. Findings may inform future strategies to support musculoskeletal health in this growing and medically vulnerable population.

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Thaer Idrees, MD, FSSCI; Phone Number: 404-251-5357; Email: thaer.idrees@emory.edu
• Study Contact Backup: Name: Jaafer Zaino; Email: jaafer.zaino@emory.edu

Study Locations

• United States
  • Georgia
    • Atlanta, Georgia, United States, 30303
      • Grady Memorial Hospital
      • Contact: Thaer Idrees, MD, FSSCI; Phone Number: 404-251-5357; Email: thaer.idrees@emory.edu
      • Principal Investigator: Thayer Idrees, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Postmenopausal women aged 65 years or older
• Has type 2 diabetes
• Body Mass Index (BMI) ≥27 kg/m² to max 40kg/m2 (inclusive)
• Hemoglobin A1c between 7-10% within 3 months of the first visit.
• Willingness and ability to comply with all study procedures, including fasting requirements for certain visits.
• No osteoporosis confirmed on DEXA scan within 12 months
• Able to provide informed consent and participate in all study assessments

Exclusion Criteria:

• Patients with type 1 diabetes mellitus or other types of diabetes that are not T2D
• eGFR <30 ml/min in the last 3 months
• Patients with a history of treatment with anti-osteoporosis agents
• Documented primary or secondary osteoporosis on a DEXA scan within the last 12 months, or are on osteoporosis therapies
• Documented presence of prosthesis or devices in the spine or hip
• Previous fragility fracture
• Males
• Moderate to severe gastroesophageal reflux disease based on patient history.
• Inability to comply with the treatment protocol or to understand the consent form.
• Aspartate aminotransferase (AST) > 3 times normal or alanine aminotransferase (ALT) > 3 times the normal
• Subjects with uncontrolled thyroid or parathyroid disease that may influence the study results.
• Personal or family history of medullary thyroid carcinoma.
• Personal or family history of multiple endocrine neoplasia type 2 syndrome.
• Personal history of gastroparesis, celiac disease, hypogonadism, severe COPD, hypopituitarism, or Cushing's disease
• Personal history of severe diabetic retinopathy.
• Known serious hypersensitivity, including anaphylaxis and angioedema, to semaglutide or any of its excipients.
• Any of the following drugs or treatments were used within 6 months before screening: treated with GLP-1RA, GIP analogues, pioglitazones or DPP-4 inhibitors
• Concomitant treatment with GLP-1 receptor agonist therapy
• Long-term intravenous, oral and intra-articular administration of high dose corticosteroids within 2 months before screening (more than 7 days in a row)
• Use of weight control drugs or surgery that can lead to weight changes during the last 6 months before screening, or are currently in the weight loss plan and are not in the maintenance stage
• Incarcerated individuals

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Type 2 Diabetics on Semaglutide; Participants will receive a GLP-1 receptor agonist (GLP-1 RA) prescribed as part of their routine clinical care. Dosing will follow standard clinical practice and will be titrated to each participant's maximum tolerated dose. The study will observe metabolic, musculoskeletal, and functional changes associated with ongoing GLP-1 RA therapy over a 6-month period.

Drug: Semaglutide; Semaglutide is an FDA-approved drug for the treatment of T2D at the following doses (0.25, 0.5, 1, and 2 mg) that is self-administered weekly using an autoinjector pen. The drug dosage will gradually increase every 4 weeks if tolerated to reach maintenance doses of 2 mg for semaglutide until the end of the study (6 months). If a participant cannot tolerate a dose, the highest tolerable dose will be administered, with continued efforts to increase the dose over time, gradually.; Other Names: GLP 1 RA

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in handgrip strength	Handgrip strength is a validated indicator of overall muscle strength and a core diagnostic component of sarcopenia. HGS will be assessed using a calibrated hydraulic hand dynamometer. Output is recorded in kilograms (kg) of force. Higher values indicate greater muscle strength	Baseline, week4, week 8, week12, week 26.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in bone turnover markers	Bone turnover markers (BTMs) reflect the rate of bone remodeling, including both bone formation and bone resorption processes. These laboratory biomarkers provide insight into dynamic skeletal changes that may occur during GLP-1 receptor agonist therapy. BTMs may include: Bone formation markers (e.g., P1NP); Bone resorption markers (e.g., CTX) Results will be reported in standard laboratory units (e.g., ng/mL, µg/L), depending on the specific assay. Higher formation markers indicate increased bone formation; higher resorption markers indicate increased bone breakdown	Baseline, 3 month, 6 months
Change in timed up-and-go (TUG)	The Timed Up and Go (TUG) test assesses functional mobility by measuring the time required for a participant to rise from a standard chair, walk to a marked 10-foot line, turn around, return to the chair, and sit down. Time is recorded in seconds (s).; Shorter times indicate better functional mobility.; Longer times may reflect impairments in balance, gait speed, or lower-extremity strength.	Baseline, week4, week 8, week12, week 26.
Change in HbA1c	Collected via venous blood sample and analyzed using standardized laboratory assays. HbA1c will be reported as a percentage (%). Reductions in HbA1c and fasting glucose reflect improved insulin sensitivity and glycemic regulation.	Baseline, 3 month, 6 months
Change in fasting glucose	Measured after an overnight fast of at least 8 hours. Fasting glucose will be reported in mg/dL. Reductions in fasting glucose reflect improved insulin sensitivity and glycemic regulation	Baseline, 6 months
Change in weight	Measured using a calibrated digital scale with participants wearing light clothing and no shoes. Body weight will be reported in kilograms (kg). Weight change (kg) will be calculated as the difference between baseline and follow-up measurements	Baseline, week4, week 8, week12, week 26.
Change in FRAX score	Fracture risk will be evaluated using the FRAX algorithm, which integrates bone mineral density (BMD) at the femoral neck with validated clinical risk factors to estimate the 10-year probability of major osteoporotic fracture and hip fracture. FRAX results are expressed as percent probabilities (%). Lower percentages indicate reduced fracture risk.	Baseline, 6 months
Change in lipid profile	Serial lipid measurements will be collected to evaluate cardiovascular risk modification during GLP-1 receptor agonist therapy. LDL-C, HDL-C, triglycerides, and total cholesterol will be reported in mg/dL.; Change in each lipid parameter will be calculated as the difference between baseline and 6-month values.; Lower LDL-C and triglycerides, along with higher HDL-C, indicate improved cardiovascular risk profiles.	Baseline, 3 months, 6 months
Changes in exercise frequency	The Community Healthy Activities Model Program for Seniors (CHAMPS) Physical Activity Questionnaire is a validated self-report tool designed to assess weekly frequency and duration of lifestyle physical activities commonly performed by older adults. It captures a broad range of activities across light, moderate, and vigorous intensities, providing a comprehensive estimate of habitual physical activity. Responses are used to calculate the total weekly frequency of various activity categories. Weekly frequency of each activity (number of sessions per week)	Baseline, 6 months
Changes in exercise duration	The Community Healthy Activities Model Program for Seniors (CHAMPS) Physical Activity Questionnaire is a validated self-report tool designed to assess weekly frequency and duration of lifestyle physical activities commonly performed by older adults. It captures a broad range of activities across light, moderate, and vigorous intensities, providing a comprehensive estimate of habitual physical activity. Responses are used to calculate the total weekly duration of various activity categories. Higher values indicate greater physical activity engagement.	Baseline, 6 months
Change in frailty assessment	Frailty will be assessed using a questionnaire based on the Fried phenotype, evaluating five components: unintentional weight loss, exhaustion, low physical activity, slowness, and weakness. A structured data capture form modeled on the validated assessment will be used. Assessment Procedure & Scoring: Completed at baseline and 6 months.; Each criterion is scored as present or absent (0-5 total).; 0: Non-frail; 1-2: Pre-frail; ≥3: Frail Interpretation: Higher scores indicate greater frailty; changes over time reflect shifts in physiologic vulnerability.	Baseline, 6 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in bone mineral density	Bone mineral density will be assessed using dual-energy X-ray absorptiometry (DEXA). Imaging will be performed at the femoral neck, total hip, and lumbar spine, which are standard anatomical sites for evaluating osteoporosis and fracture risk. BMD will be reported in grams per square centimeter (g/cm²). Z-scores reflect how a participant's bone density compares with expected values for individuals of the same demographic profile. Lower Z-scores may indicate reduced bone density and increased susceptibility to osteopenia or osteoporosis.	Baseline, 6 months

Collaborators and Investigators

• Sponsor: Emory University
• Collaborators: National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
• Investigators: Principal Investigator: Thaer Idrees, MD, FSSCI, Emory University

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2026
• Primary Completion (Estimated): November 1, 2028
• Study Completion (Estimated): November 1, 2028

Study Registration Dates

• First Submitted: February 17, 2026
• First Submitted That Met QC Criteria: February 17, 2026
• First Posted (Actual): February 24, 2026

Study Record Updates

• Last Update Posted (Actual): February 24, 2026
• Last Update Submitted That Met QC Criteria: February 17, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: Semaglutide; Bone Mineral Density; DEXA; Bone turnover markers; Osteosarcopenia; GLP-1 Receptor analogs
• Additional Relevant MeSH Terms: Endocrine System Diseases; Metabolic Diseases; Glucose Metabolism Disorders; Diabetes Mellitus; Nutritional and Metabolic Diseases; Diabetes Mellitus, Type 2; semaglutide
• Other Study ID Numbers: 2025P013673; K12AR084234 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes