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

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