Clinical trial NCT06885736: LEAN Mass Preservation With Resistance Exercise and Protein During Semaglutide/Tirzepatide Therapy
Official title: LEAN Mass Preservation With Resistance Exercise and Protein During Semaglutide and Tirzepatide Therapy (LEAN-PREP Study)
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Type 2 Diabetes Mellitus (T2DM)
Keywords: Obesity, research
Lead sponsor: Dasman Diabetes Institute
Sponsor class: OTHER
Collaborators: name: University of Glasgow
First posted: 2025-03-20
Enrollment: 232
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This will be a 6-month 4 arm (control, resistance exercise, protein intake and resistance exercise + protein intake) randomised controlled trial in people with type 2 diabetes upon initiation of semaglutide/tirzepatide therapy.
Primary purpose: BASIC_SCIENCE

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.


Eligibility criteria: 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

Primary outcomes:
measure: MRI measured quadriceps cross sectional area (CSA)
timeFrame: From enrollment (at baseline) to the end of treatment at 6 months.
Secondary outcomes:
measure: MRI measured liver fat
timeFrame: From enrollment (at baseline) to the end of treatment at 6 months.
measure: MRI measured intramuscular fat content (total thigh)
timeFrame: From enrollment (at baseline) to the end of treatment at 6 months.
measure: Muscle strength
timeFrame: From enrollment (at baseline) to the end of treatment at 6 months.
measure: Energy intake
timeFrame: From enrollment (at baseline) to the end of treatment at 6 months.
measure: Physical activity and sleep levels
timeFrame: From enrollment (at baseline) to the end of treatment at 6 months.
measure: Activities of Daily Living
timeFrame: From enrollment (at baseline) to the end of treatment at 6 months.
measure: Whole blood glycated haemoglobin (HbA1c)
timeFrame: From enrollment (at baseline) to the end of treatment at 6 months.
measure: Oral glucose tolerance test
timeFrame: From enrollment (at baseline) to the end of treatment at 6 months.
measure: Blood lipids
timeFrame: From enrollment (at baseline) to the end of treatment at 6 months.
measure: Liver function
timeFrame: From enrollment (at baseline) to the end of treatment at 6 months.
measure: Plasma GLP-1 and GIP
timeFrame: From enrollment (at baseline) to the end of treatment at 6 months.
measure: Concomitant medication
timeFrame: From enrollment (at baseline) to the end of treatment at 6 months.
measure: Fib-4 score
timeFrame: From enrollment (at baseline) to the end of treatment at 6 months.
measure: hsCRP
timeFrame: From enrollment (at baseline) to the end of treatment at 6 months.
measure: IL-6, IL-10, IL1Ra and TNF-alpha.
timeFrame: From enrollment (at baseline) to the end of treatment at 6 months.
measure: Gait Speed
timeFrame: From enrollment (at baseline) to the end of treatment at 6 months.
measure: Chair rise performance
timeFrame: From enrollment (at baseline) to the end of treatment at 6 months.
measure: Aerobic Fitness
timeFrame: From enrollment (at baseline) to the end of treatment at 6 months.
measure: Macronutrient Intake
timeFrame: From enrollment (at baseline) to the end of treatment at 6 months.
measure: Quality of Life assessed using the EQ-5D-5L questionnaire
timeFrame: From enrollment (at baseline) to the end of treatment at 6 months.
measure: Body Composition via DEXA scan
timeFrame: From enrollment (at baseline) to the end of treatment at 6 months.
Other outcomes:
Locations:
Study officials:
References:
citation: Morton RW, Murphy KT, McKellar SR, Schoenfeld BJ, Henselmans M, Helms E, Aragon AA, Devries MC, Banfield L, Krieger JW, Phillips SM. A systematic review, meta-analysis and meta-regression of the effect of protein supplementation on resistance training-induced gains in muscle mass and strength in healthy adults. Br J Sports Med. 2018 Mar;52(6):376-384. doi: 10.1136/bjsports-2017-097608. Epub 2017 Jul 11.
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citation: Lundgren JR, Janus C, Jensen SBK, Juhl CR, Olsen LM, Christensen RM, Svane MS, Bandholm T, Bojsen-Moller KN, Blond MB, Jensen JB, Stallknecht BM, Holst JJ, Madsbad S, Torekov SS. Healthy Weight Loss Maintenance with Exercise, Liraglutide, or Both Combined. N Engl J Med. 2021 May 6;384(18):1719-1730. doi: 10.1056/NEJMoa2028198.
citation: Westcott WL. Resistance training is medicine: effects of strength training on health. Curr Sports Med Rep. 2012 Jul-Aug;11(4):209-16. doi: 10.1249/JSR.0b013e31825dabb8.
citation: Umpierre D, Ribeiro PA, Kramer CK, Leitao CB, Zucatti AT, Azevedo MJ, Gross JL, Ribeiro JP, Schaan BD. Physical activity advice only or structured exercise training and association with HbA1c levels in type 2 diabetes: a systematic review and meta-analysis. JAMA. 2011 May 4;305(17):1790-9. doi: 10.1001/jama.2011.576.
citation: Al Ozairi E, Alsaeed D, Al Roudhan D, Jalali M, Mashankar A, Taliping D, Abdulla A, Gill JMR, Sattar N, Welsh P, Gray SR. The effect of home-based resistance exercise training in people with type 2 diabetes: A randomized controlled trial. Diabetes Metab Res Rev. 2023 Oct;39(7):e3677. doi: 10.1002/dmrr.3677. Epub 2023 Jun 17.