Study of a DPP 4 inhibitor and an SGLT2 inhibitor used together compared with each treatment alone in adults with type 2 diabetes treated with metformin.

Prior treatment

• Acute coronary syndrome (non-ST elevation myocardial infarction, ST elevation myocardial infarction and unstable angina pectoris), stroke or TIA within 3 months prior screening.
• Use of antidiabetic drugs (other than metformin) within 12 weeks prior to screening.
• Use of any concomitant medication that could have any potential clinically significant drug interaction with the study treatments.
• Requirement of GLP-1 receptor agonist therapy according to the treating physician and local standard of care, unless GLP-1 receptor agonist therapy is contraindicated, not tolerated, or declined by the participant after appropriate medical counselling.
• Participation in weight-loss programs and/or use of weight-loss medications in the last 12 weeks.
• Participation in another trial where an investigational drug (non-antidiabetic) has been administered within 90 days prior to planned administration of trial medication, or current participation in another trial involving administration of investigation drug.

Other illness

• Severe allergy to study drugs, their classes, or excipients.
• Severe liver disease, defined as a Child-Pugh score > 9 (10 to 15), corresponding to Child-Pugh class C.
• Essential hypertension diagnosed and treated but uncontrolled, defined as systolic blood pressure (SBP) ≥160 mmHg and/or diastolic blood pressure (DBP) ≥100 mmHg despite ongoing antihypertensive therapy
• History of malignancies in the last 5 years (except in situ or basal/squamous cell skin cancer).
• Evidence of active HBV, HCV and HIV-1 and/or HIV-2 infection, defined as HBsAg positivity for hepatitis B or detectable HCV RNA for hepatitis C, or uncontrolled HIV-1 and/or HIV-2 infection, including disease meeting AIDS-defining criteria.
• Any medical, psychiatric, behavioral, or social circumstance not otherwise covered by the exclusion criteria that is likely to prevent completion of study procedures, compromise protocol compliance, or substantially affect the quality or interpretation of study data.
• History of alcohol, or drug abuse within the past year.
• History or presence of any clinically significant medical or psychiatric condition not specifically addressed by the other exclusion criteria that, in the opinion of the Investigator, would: increase the risk associated with study participation, interfere with protocol compliance, or confound interpretation of study outcomes.
• History of Type 1 diabetes or secondary diabetes.

Lab values

• Moderate (eGFR of 30 - <60 mL/min/1.73 m²) to severe (eGFR <30 mL/min/1.73 m²) renal impairment.
• History of congestive heart failure NYHA classification class III/IV, or unstable or acute congestive heart failure. Patients with atherosclerotic cardiovascular disease and heart failure with reduced or preserved ejection fraction NYHA classification class II should also be excluded, unless GLP-1 receptor agonist therapy is contraindicated, not tolerated, or declined by the participant after appropriate medical counselling.
• Clinically significant ECG abnormalities at screening that, in the opinion of the Investigator, indicate unstable cardiovascular disease, clinically relevant arrhythmias, second- or third-degree atrioventricular block (unless treated with a functioning pacemaker), QTc prolongation (>500 ms), or any abnormality considered to increase the risk of study participation.
• Diabetic kidney disease (DKD), defined as an albumin-to-creatinine ration (ACR) ≥ 30mg/g, based on two measurements prior to randomization.
• Confirmed fasting plasma glucose (FPG) > 240 mg/dL (>13.3 mmol/L) after an overnight fast (minimum 8 hours), based on two measurements prior to randomization.

Other

• Smoking of more than 10 cigarettes or 3 cigars or 3 pipes per day at screening.
• Institutionalized participants.
• Pregnant or lactating participants.

• Male or non-pregnant, non-lactating female participants aged ≥18 years at the time of signing the Informed Consent Form (ICF), with a diagnosis of T2DM.
• Persistent hyperglycemia while on a stable regimen of metformin (≥ 1500 mg/day or maximum tolerated/local labelled dose) and diet and exercise regimen for at least 12 weeks prior to screening.
• HbA1c ≥ 7.0% and ≤ 10.5% (≥ 53.0 mmol/mol to ≤ 91.3 mmol/mol) at screening.
• BMI ≤ 45 kg/m² at screening.
• eGFR ≥ 60 mL/min/1.73 m².
• Able to swallow oral medication.
• A female (applicable to woman of childbearing potential (WOCBP)), is eligible to participate if she is not pregnant - must have a negative serum pregnancy test before randomization. A negative urine pregnancy test is obligatory prior to the start of the IMP.
• A WOCBP who agrees to use one highly effective contraceptive method, during the treatment period and for at least 2 weeks after the last dose of study treatment for participants early terminating the study or EoT visit for participants completing the Week 52 (according to CTFG 21/09/2020 Version 1.2). No specific contraceptive measures are required for male participants. Based on the available non-clinical and clinical data, the risk of effects on pregnancy or the unborn child resulting from exposure through a male participant is considered minimal.
• The participant is capable of providing signed written ICF prior to the initiation of any study-related procedures, including but not limited to data collection, source data verification, and any other assessments or interventions associated with the clinical trial in accordance with local requirements.