LEAN Mass Preservation With Resistance Exercise and Protein During Semaglutide/Tirzepatide Therapy

Not Applicable

Not yet recruiting

• Conditions: Type 2 Diabetes Mellitus (T2DM)

• Registration Number: NCT06885736
• Lead Sponsor: Dasman Diabetes Institute

Brief Summary

The aim of the current study is to determine whether resistance exercise and/or protein intake can preserve lean mass and improve physical function in patients with type 2 diabetes initiating semaglutide/tirzepatide therapy. To achieve this aim the study will have the following objectives.

In people with type 2 diabetes initiating semaglutide/tirzepatide therapy

1. Form a PPI group to refine the study protocol and establish study materials,

2. Quantify the effects of a pragmatic resistance exercise intervention and/or increasing protein intake on lean mass and physical function during semaglutide/tirzepatide induced weight loss,

3. Establish whether the resistance exercise intervention and/or increasing protein intake has concomitant benefits on glycaemic control, lipids, liver function, quality of life, physical activity and sleep during semaglutide/tirzepatide induced weight loss.

The participants will:

Begin their weight loss medication, starting at a low dose and then increasing the dose to maximize weight loss. They will be randomly assigned by a computer to ONE of the following groups and will be followed up to 6-months:

* Control group

* Protein intake group

* Muscle strengthening exercise group

* Muscle strengthening exercise AND protein intake group.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2025-03-09
• Study First Submitted QC: 2025-03-13
• Study First Posted: 2025-03-20
• Status Verified: 2025-05
• Last Update Submitted: 2025-05-14
• Last Update Posted: 2025-05-18
• Study Start: 2025-06-10
• Primary Completion: 2029-06-30
• Study Completion: 2029-12-31

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 232

Inclusion Criteria

• Physician confirmed type 2 diabetes.
• Age >/= 18 years
• BMI 25-45

Exclusion Criteria

• Currently or in the past 6 months participating in any vigorous aerobic activity (>1h per week) or any resistance exercise.
• BP of 160/100mmHg or higher
• Insulin therapy
• Any known medical condition that prevents participants from exercising safely
• A personal or family history of medullary thyroid carcinoma
• Multiple Endocrine Neoplasia syndrome type 2 (MEN 2)
• History of chronic or acute pancreatitis
• History of proliferative diabetic retinopathy or diabetic maculopathy
• History of ketoacidosis or hyperosmolar state/coma
• History of severe hypoglycaemia and/or hypoglycaemia unawareness within last 6 onths
• Clinically significant gastric emptying abnormality or have undergone or plan to undergo gastric bypass or restrictive bariatric surgery or chronically taking drugs that directly affect GI motility
• Any of the following CV conditions in last 2 months: acute MI, stroke or hospitilisation due to CHF
• History of NYHA IV CHF
• Acute or chronic hepatitits, signs and symptoms of any liver disease other than NAFLD, ALT > 3 times the upper limit of normal
• eGFR <45mL/min/1.73m2
• Significant uncontrolled endocrine abnormaility in the opinion of clinical investigator
• Serum calcitonin >35ng/L
• Evidence of active autoimmune abnormality that is likely to requite systemic glucocorticoid treatment in the next 12 months
• Had or waiting for an organ transplant
• History of an active or untreated malignancy or in remission from a clinically significant malignancy for less than 5 years
• Any other aspect of history or condition that may limit the ability of the patient to complete the study
• Having been treated with prescription drugs that promote weight loss in the last 3 months
• Receiving chronic systemic glucocorticoid therapy within last month

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
MRI measured quadriceps cross sectional area (CSA)	From enrollment (at baseline) to the end of treatment at 6 months.	At the mid-point of the thigh, we will measure the cross-sectional area of the quadriceps muscle and quantify muscle's thickness and size.

Secondary Outcome Measures

Name	Time	Method
Quality of Life assessed using the EQ-5D-5L questionnaire	From enrollment (at baseline) to the end of treatment at 6 months.	This will be quantified by the EQ-5D-5L questionnaire.
Body Composition via DEXA scan	From enrollment (at baseline) to the end of treatment at 6 months.	fat and fat free mass via Dual Energy X-ray Absorptiometry (DEXA)
MRI measured liver fat	From enrollment (at baseline) to the end of treatment at 6 months.	We will also assess liver fat using an IDEAL scan.
MRI measured intramuscular fat content (total thigh)	From enrollment (at baseline) to the end of treatment at 6 months.	We will quantify intramuscular fat content
Muscle strength	From enrollment (at baseline) to the end of treatment at 6 months.	Grip strength will be measured 3 times in each hand using a Jamar dynamometer.
Energy intake	From enrollment (at baseline) to the end of treatment at 6 months.	Baseline energy intake will be quantified by the use of the EPIC food frequency questionnaire and multi-pass 24h recall. Further 24h recalls will be carried out at 0.5,1,3 and 6 months of the follow up period.
Physical activity and sleep levels	From enrollment (at baseline) to the end of treatment at 6 months.	Participants will be asked to wear and accelerometer for a 7-day period to quantify physical activity and sedentary behaviour. The accelerometer is a wrist born watch and we will ask participants to wear this device for 24h a day for the 7-day measurement period. We will use tri-axial accelerometers and following data collection we will process the accelerometer counts using R software and generate the daily amount of light, moderate and vigorous physical activity along with sleep.
Activities of Daily Living	From enrollment (at baseline) to the end of treatment at 6 months.	This will be quantified by the Barthel activities of daily living questionnaire.
Whole blood glycated haemoglobin (HbA1c)	From enrollment (at baseline) to the end of treatment at 6 months.
Oral glucose tolerance test	From enrollment (at baseline) to the end of treatment at 6 months.	An oral glucose tolerance test will be performed with a cannula inserted and a baseline blood sample collected, a 75g glucose load consumed and further samples collected at 15, 30, 60 90 and 120 min. Samples will be analysed for glucose and insulin levels.
Blood lipids	From enrollment (at baseline) to the end of treatment at 6 months.
Liver function	From enrollment (at baseline) to the end of treatment at 6 months.	We will measure aspartate amino transferase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), albumin (ALB), total protein (TP), gamma-glutamyltransferase (GGT) and bilirubin.
Plasma GLP-1 and GIP	From enrollment (at baseline) to the end of treatment at 6 months.
Concomitant medication	From enrollment (at baseline) to the end of treatment at 6 months.
Fib-4 score	From enrollment (at baseline) to the end of treatment at 6 months.	Fib-4 score will be calculated from liver function test
Gait Speed	From enrollment (at baseline) to the end of treatment at 6 months.	Habitual gait speed will be measured during a 4 metre walk test
Chair rise performance	From enrollment (at baseline) to the end of treatment at 6 months.	The number of chair rises completed in 30 seconds measured.
Aerobic Fitness	From enrollment (at baseline) to the end of treatment at 6 months.	Aerobic fitness will be quantified with the 6 min walk test.
hsCRP	From enrollment (at baseline) to the end of treatment at 6 months.
IL-6, IL-10, IL1Ra and TNF-alpha.	From enrollment (at baseline) to the end of treatment at 6 months.
Macronutrient Intake	From enrollment (at baseline) to the end of treatment at 6 months.	Baseline carbodhyrate, fat and protein intake (all g/day) will be quantified by the use of the EPIC food frequency questionnaire and multi-pass 24h recall. Further 24h recalls will be carried out at 0.5,1,3 and 6 months of the follow up period.