Semaglutide plus exercise to reduce fat in the heart and leg muscles.

Intramyocellular Lipid Compartments After Glucagon-like Peptide 1 Receptor Agonist Therapy in Type 2 Diabetes - Rebalancing the Fat Content of the Heart and Muscles

This will test if semaglutide plus a supervised resistance and endurance exercise program reduces fat inside the heart and leg muscles in adults with type 2 diabetes who are overweight and not meeting activity guidelines.

Quick facts

• Phase: NA
• Study type: Interventional
• Enrollment: 60 (estimated)
• Ages: 20 Years to 75 Years
• Sex: All
• Sponsor: University of Aberdeen (other)
• Locations: 1 site (Aberdeen, Aberdeenshire)
• Trial ID: NCT07065383 on ClinicalTrials.gov

What this trial studies

This interventional trial randomises adults with recent type 2 diabetes to semaglutide plus standard dietary counselling and general activity advice versus semaglutide plus a personalised, supervised programme of resistance and endurance exercise. Imaging scans will measure fat content in the heart and leg muscles before and after the intervention. Eligible participants are 20–75 years old, diagnosed within 10 years, have BMI ≥27 kg/m2, HbA1c ≥7% and are not on insulin, and currently do not meet WHO physical activity recommendations. The programme is delivered at Aberdeen Royal Infirmary and includes supervised exercise sessions and follow-up visits.

Who should consider this trial

Good fit: Adults 20–75 years with type 2 diabetes diagnosed within the past 10 years, BMI ≥27 kg/m2, HbA1c ≥7% not on insulin, insufficient physical activity, weight under 140 kg, eGFR >30 mL/min/1.73m2, and able to attend the Aberdeen site are ideal candidates.

Not a fit: Patients with known coronary artery disease or other significant/untreated cardiac conditions, those on insulin, with very low kidney function, or unable to attend supervised sessions are unlikely to benefit from this protocol.

Why it matters

Potential benefit: If successful, this approach could reduce harmful fat in the heart and muscles and improve cardiovascular health and physical fitness in people with type 2 diabetes.

How similar studies have performed: Large trials have shown GLP-1 agonists like semaglutide cause weight loss and cardiovascular benefit, but using semaglutide combined with supervised exercise specifically to reduce heart and muscle fat is a relatively new approach.

Eligibility criteria

Inclusion Criteria:

* Patients with a confirmed diagnosis of type 2 diabetes established in the previous 10 years between the ages of 20 and 75
* HbA1c ≥ 53 mmol/mol (7%) typically on diet and/or metformin/sulphonylureas (and/or sodium-glucose cotransporter-2 inhibitors, Dipeptidyl peptidase 4 inhibitors, thiazolidinediones, but not on insulin)
* Patients who do not meet the WHO recommendations on physical activity (≤150 minutes per week) of moderate-vigorous physical activity (MVPA)
* Patients who have a BMI of ≥27 but with a body weight of less than 140kgs due to limitations of the scanner table weight limit
* Current or recent (within 3 months) eGFR \>30 mL/min/1.73m2)
* Able to understand written and spoken English

Exclusion Criteria:

* Any previously unknown cardiac condition other than mild valvular disease
* Any history of known coronary artery disease (including myocardial infarction and myocardial infarction with normal coronary arteries)
* Any relevant or untreated endocrine condition (i.e. Cushings)
* Impaired renal function (defined as estimated glomerular filtration rate of less than 30 mL/min/1.73m2)
* Blood pressure of more than 180/100 mmHg
* Patients on any other medication known to influence glucose or fatty acids metabolism (niacin, omega-3 fatty acids, other glucagon-like peptide-1 receptor agonists)
* Patients with any dietary habits that may interfere with the investigation (for example high fat vegan diets, as we know form prior research that they have very different intramyocellular fat storage compared to those on no dietary preferences)
* Patients with any history of any medical or surgical condition that in the judgement of the investigators may interfere with the exercise regime (i.e. peripheral vascular disease, arthritis), fatty acids metabolism (i.e. lipid storage diseases) or may compromise the safety of the participant (i.e. neurological syndromes for whom an intense exercise program could result in musculo-skeletal injury or accidents due to loss of balance).
* Patients with a sensitivity to Semaglutide (known hypersensitivity, diabetic retinopathy, pregnancy, history of pancreatitis or history of any cancer)
* Significant asthma or pulmonary disease
* Participants unable to cycle on the ergometer
* Unable to perform exercise testing (e.g. prosthetic limbs)
* Pregnancy, breastfeeding or considering pregnancy.
* Patients who have recently had gastrointestinal contrast or radionuclides
* Inability to lie flat or remain motionless for scanning procedures
* Patients whose girth size cannot allow them to fit in the magnetic resonance scanner (there is no set location to measure as this is different for everyone, but we have a plastic hoop that can be fitted around the largest circumference to check the fit)
* Subjects who are not able to engage into a physical training regime or feel that they do not have the interest or sustained motivation to follow one.
* Participants currently enrolled in other interventional clinical research
* Participants not able to understand written or verbal English

Where this trial is running

Aberdeen, Aberdeenshire

• Cardiac Research Office, Aberdeen Royal Infirmary — Aberdeen, Aberdeenshire, United Kingdom (RECRUITING)

Study contacts

• Principal investigator: Dana Dawson, DM — University of Aberdeen
• Study coordinator: Alexander Davidson, DM

Conditions: Diabetes Mellitus Type 2