LEAN Mass Preservation with Resistance Exercise and Protein During Semaglutide/Tirzepatide Therapy (LEAN-PREP)

Dasman Diabetes Institute

Status: Not yet enrolling

Conditions: Type 2 Diabetes Mellitus (T2DM)

Treatments: Combination Product: Resistance exercise + protein intake; Behavioral: Resistance exercise; Dietary Supplement: Protein Intake

Study type: Interventional

Funder types: Other

Identifiers

NCT06885736

RA HM-2025-01

Details and patient eligibility

About

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.

Enrollment: 232 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Basic Science

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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232 participants in 4 patient groups

Resistance exercise

Experimental group

Description:

Participants assigned to the resistance exercise group will be asked to perform exercises 3 times a week for the intervention period. The first 3 sessions of the exercise will be performed under the supervision of a qualified exercise specialist to ensure that the participants are happy with the exercises and are performing them appropriately. These will also be group sessions to encourage participants to build social connections to support them during the intervention. A similar group social session will take place at week 4 and then every 4 weeks of the study to overcome any issues with the exercises and to ensure progression to an appropriate intensity.

Treatment:

Behavioral: Resistance exercise

Protein Intake

Experimental group

Description:

The aim of this arm of the intervention is to ensure a protein intake of 1.6g/kg/day, as this was the intake level identified as the level after which no further effect was found on muscle mass in the meta-regression from (Morton et al., 2018). For the initial 2 weeks of the study, we will ask participants to consume 2 protein drinks, containing 25g protein (3g leucine), per day - one in the morning and one in the evening. At this stage, we won't know the magnitude of reduction of protein intake following initiation of semaglutide/tirzepatide treatment. After 2 weeks, when the first assessment of dietary intake after beginning semaglutide/tirzepatide treatment occurs, the additional protein will be based on the amount required to ensure 1.6g/kg/day with an aim to spread protein evenly across the day and aim for at least 25g protein (3g leucine) per meal or snack.

Treatment:

Dietary Supplement: Protein Intake

Resistance exercise + protein intake

Experimental group

Description:

Participants in this arm will follow the above resistance exercise and protein intake interventions.

Treatment:

Dietary Supplement: Protein Intake

Combination Product: Resistance exercise + protein intake

Control

No Intervention group

Description:

Participants assigned to the control group will be asked to maintain their usual exercise habits