SGLT2 Inhibitor or Metformin as Standard Treatment of Early Stage Type 2 Diabetes

A Multicenter, Register-based, Randomized, Controlled Trial Comparing Dapagliflozin With Metformin Treatment in Early Stage Type 2 Diabetes Patients by Assessing Mortality and Macro- and Microvascular Complications

A real-world, nationwide, register-based, randomised trial (RRCT) comparing SGLT2 inhibitors with metformin as standard treatment in early typ 2 diabetes. An open-label trial addressing efficacy with respect to clinically important macro- and microvascular events.

2067 type 2 diabetes (T2D) patients on monotherapy or drug naive. Randomization 1:1, metformin, dosing according to treatment guidelines or SGLT2 inhibitor, dapagliflozin 10 mg od.

844 events estimated for study completion (90% power to detect hazard ratio (HR) <0.8 for dapagliflozin vs metformin ) Endpoint collection during study duration (about 4 years) from national health care registers: Patient, Prescribed drugs, Cause of death and Population registers; National diabetes register (NDR) Primary analysis according to insulin tolerance test (ITT)

Inclusion Criteria:

• Men and women ≥18 years old
• T2D (according to World Health Organization (WHO) criteria) of less than 4 years duration
• BMI 18.5-45 kg/m2
• Drug naïve or oral monotherapy with glucose-lowering drug.
• Accepting NDR participation and other register data collection.

Exclusion Criteria:

• Known or suspected other form of diabetes than type 2
• Ongoing or more than >4 weeks in total of any previous treatment with: insulin, GLP-1 receptor agonists, SGLT2 inhibitors or combination of any diabetes medications
• Medical need to start or intensify any specific GLD treatment, e.g. insulin due to marked hyperglycemia
• HbA1c >70 mmol/mol for patients on monotherapy, >80 in drug naïve
• Contraindication to either metformin or dapagliflozin, or any unacceptable risk with either treatment as assessed by the investigator
• History or signs of established cardiovascular disease: diagnosis of myocardial infarction, angina pectoris, heart failure, stroke, lower extremity arterial disease, any limb amputation (except due to trauma or malignancy)
• Any serious illness or other condition with short life expectancy (<4 yr)
• Renal impairment (eGFR <60 ml/min/1,73m2)
• Any condition, as judged by the investigator, that suggests that the patient will be non-compliant or otherwise unsuitable to study medication or study participation
• Pregnancy or breastfeeding, women of childbearing potential (WOCBP; including perimenopausal women who have had a menstrual period within 1 year) without adequate anticonception during any part of the study period
• Involvement in the planning and/or conduct of the study
• Ongoing participation in another clinical trial.