Myocardial Insulin Resistance in Type 2 Diabetes: Effects of Semaglutide vs Dapagliflozin on Cardiac Function Assessed by 18F‑FDG PET/CT and 99mTc‑Tetrofosmin SPECT

The study aims to determine, by means of 18F‑FDG PET/CT and 99mTc‑Tetrofosmin SPECT, whether myocardial insulin resistance affects cardiac function and coronary flow, establishing it as a risk factor for cardiovascular events and diabetic cardiomyopathy in patients with type 2 diabetes displaying a myocardial IR phenotype.

Secondary objectives:

• Identify metabolomic and lipidomic biomarkers linked to myocardial insulin resistance, cardiac function, and coronary flow to support personalized management of the disease.
• Evaluate the effects of the GLP‑1RA semaglutide and the SGLT2i dapagliflozin on myocardial insulin resistance.

The trial enrolled adult patients with Type 2 diabetes who exhibited a myocardial ischemia‑reperfusion (IR) phenotype. Both female and male participants were eligible; however, the sponsor did not provide the total number of enrolled subjects. Age eligibility was defined by internal coding categories (codes 3 and 4), with specific age limits not disclosed. Inclusion required a BMI approximating 30 kg/m², HbA1c values between 7 % and 9 %, and abstinence from smoking and alcohol use. Participants were otherwise required to be in general good health apart from the diabetic condition and the myocardial IR phenotype.

The study is a controlled clinical investigation comparing a GLP‑1RA (semaglutide 1 mg subcutaneously) with an SGLT2i (dapagliflozin 10 mg orally) in participants with type 2 diabetes who meet the inclusion criteria of a body‑mass index around 30 kg/m², HbA1c 7–9 %, and abstinence from smoking and alcohol. After an initial screening visit to confirm eligibility, participants are allocated to either the test or comparator arm and receive the assigned medication throughout the treatment period. Serial assessments are performed using 18F‑FDG PET/CT and 99mTc‑Tetrofosmin SPECT to evaluate the primary endpoint of myocardial insulin resistance and secondary endpoints of coronary flow and cardiac function. Follow‑up visits are scheduled at regular intervals to monitor safety, adherence, and imaging outcomes, culminating in an end‑of‑study visit that finalizes data collection. Participant involvement extends from the screening visit through the end‑of‑study visit, with the overall trial spanning from the projected recruitment start on 2 April 2026 to the estimated completion on 30 September 2027.

The investigational product is semaglutide provided as Ozempic 1 mg solution for injection in a pre‑filled pen. The formulation is a solution for subcutaneous administration, delivering a dose of 375 000 µg (equivalent to 1 mg) per injection. Participants receive the injection once weekly throughout the treatment period. Injection technique is standardized, and the pre‑filled pen includes a dose‑setting mechanism to ensure accurate delivery. Adherence to the weekly schedule is monitored by electronic injection logs and periodic verification of pen usage.

The active comparator is dapagliflozin supplied as 10 mg film‑coated tablets. The tablets are administered orally, with a single 10 mg dose taken each day. Tablet intake is recorded in a daily medication diary and compliance is assessed by tablet count at each study visit. Both the investigational and comparator agents are administered in addition to standard background therapy for type 2 diabetes as required by the protocol.

Efficacy will be evaluated using the primary endpoint of myocardial insulin resistance, quantified by 18F‑FDG PET/CT imaging. Secondary efficacy endpoints include coronary flow and heart function, which will be assessed with 99mTc‑Tetrofosmin SPECT imaging. All imaging procedures will be performed according to the study protocol, and the resulting quantitative parameters will be analyzed to determine the impact of the investigational GLP‑1 receptor agonist and SGLT2 inhibitor on myocardial insulin resistance, coronary perfusion, and cardiac performance.