SEMAGLUTIDE for Type 2 diabetes mellitus|Cardiovascular autonomic neuropathy

Inclusion criteria

• {"criterion_text":"- Informed consent obtained before any study-specific procedures. Patients must be able to understand and be willing to sign a written informed consent\n- Patients who are intolerant to metformin, or in metformin failure, or present clinical indications for initiating SGLT2 inhibitor therapy (e.g., heart failure, diabetic kidney disease), in accordance with current clinical guidelines\n- Men and women with type 2 diabetes mellitus\n- age > 45 years old\n- patients with stable medical therapy including other anti-hyperglycemic agents alone or in combination with a basal insulin analogue for at least 3 months prior to the screening visit (including stable insulin dose defined as no variation over 30% in daily insulin dose in the preceding 3 months, as evaluated by the Investigator)\n- HbA1c above or equal to 7.0% but less than 8.5% at screening\n- Women of childbearing potential must have a negative blood or urine pregnancy test at the baseline visit\n- Female subjects of childbearing potential must be willing to use an adequate method of contraception as outlined in Section 5.9 of the protocol\n- Ability to take oral medications\n- Will and ability to comply with the protocol"}

Exclusion criteria

• {"criterion_text":"- Type 1 diabetes mellitus\n- chronic obstructive lung disease with evidence of bronchospasm (e.g. asthma)\n- long QT syndrome\n- severe hypotension\n- decompensated heart failure\n- History of diabetic ketoacidosis (DKA), unless a clear and modifiable precipitating factor (e.g., ketogenic diet, excessive alcohol consumption) has been identified and eliminated\n- Female during pregnancy and breastfeeding\n- Certified or suspected hypersensitivity to SGLT2 inhibitors\n- Patients on dialysis or with estimated glomerular filtration rate (eGFR) below the following thresholds, depending on the assigned treatment: - eGFR <45 mL/min/1.73 m² for patients planned to receive ertugliflozin - eGFR <30 mL/min/1.73 m² for patients planned to receive empagliflozin, canagliflozin, or dapagliflozin;\n- diagnosis of chronic obstructive pulmonary disease or respiratory failure\n- inability to provide informed consent\n- patients with history of breast, bladder and prostate cancer\n- previous diagnosis of Latent Autoimmune Diabetes of Adults (LADA)\n- use of SGLT-2is in the 90 days prior to screening, acute decompensation of glycemic control requiring immediate intensification of treatment to prevent acute complications (e.g. diabetic ketoacidosis) in 90 days prior to screening\n- acute coronary or cerebro-vascular event in the 90 days prior to randomization, currently planned coronary, carotid or peripheral artery revascularization, NYHA class III or IV, unstable angina\n- sick sinus syndrome, second or third degree atrio-ventricular block (except in patients with a functioning artificial pacemaker)"}

Primary endpoints

• {"endpoint_text":"- Endpoint related to Objective #1: to verify the effect of SGLT-2is on HRV as shown by the difference in LF:HF ratio (a frequency domain measured as improvement of 20% in LF:HF ratio from baseline to end of treatment (6 months).","definition_or_measurement_approach":"LF:HF ratio (frequency domain heart rate variability); measured as percentage of patients with an improvement of 20% from baseline to end of treatment (6 months)."}
• {"endpoint_text":"- Endpoint related to Objective #2: to verify the effect of SGLT-2 on CAN progression as shown by the improvement in at least one of the three CART parameter AND an improvement in glucose variability from baseline to end of treatment (6 months)","definition_or_measurement_approach":"Improvement in at least one of the three CART parameters combined with an improvement in glucose variability from baseline to end of treatment (6 months). CART parameters referenced in protocol (see secondary endpoints) include E/I ratio, 30:15 ratio and Valsalva ratio."}

Secondary endpoints

• {"endpoint_text":"- to assess the results of SGLT2i treatment on pancreatic beta cell function (i.e., glucose sensitivity and insulin secretion parameters including those derived from the Mixed Meal Test (MMT)) in patients with and without CAN after 6 months intervention with SGLT2i.","definition_or_measurement_approach":"Assessment of pancreatic beta cell function using glucose sensitivity and insulin secretion parameters derived from the Mixed Meal Test (MMT) after 6 months of intervention."}
• {"endpoint_text":"- to assess the difference in glycemic variability expressed as mean amplitude of glycemic excursions (MAGE) measured for 2 weeks flash glucose monitoring at baseline and after 6 months of treatment with SGLT-2i.","definition_or_measurement_approach":"Mean amplitude of glycemic excursions (MAGE) measured by 2 weeks of flash glucose monitoring at baseline and after 6 months of SGLT-2i treatment."}
• {"endpoint_text":"- to explore difference in CAN progression expressed as changes in cardiovascular autonomic reflex tests (CARTs) as defined by: a) expiration/inspiration (E/I) ratio, b) 30:15 ratio and c) Valsalva ratio.","definition_or_measurement_approach":"Changes in CARTs: E/I ratio, 30:15 ratio and Valsalva ratio to quantify CAN progression."}

Italy

Earliest CTIS Part Ii Submission Date

24-04-2025

Latest Decision Or Authorization Date

09-12-2025

Processing Time Days

229

Number Of Sites

2

Number Of Participants

80

Primary sponsor

Full Name

Universita Cattolica Del Sacro Cuore

Organisation Type

Educational Institution

Country Of Registered Address

Italy