NCT03982381.

Study name	SMARTEST
Methods	Type of trial: efficacy trial Allocation: randomised Intervention model: parallel assignment Masking: single (outcomes analysis team) Primary purpose: treatment
Participants	Condition: T2DM Enrollment: estimated 4300 Inclusion criteria: men and women ≥18 years old, T2DM (according to World Health Organization (WHO) criteria) of less than 4 years duration, BMI 18.5 to 45 kg/m2, drug‐naive 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 glucose‐lowering drug treatment, e.g. insulin due to marked hyperglycaemia, HbA1c >70 mmol/mol for patients on monotherapy, > 80 in drug‐naive, 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 years), renal impairment (estimated glomerular filtration rate < 60 mL/min/1.73 m2), 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 (including perimenopausal women who have had a menstrual period within 1 year) without adequate anti‐conception during any part of the study period, involvement in the planning and/or conduct of the study, ongoing participation in another clinical trial.
Interventions	Intervention(s): metformin (1000 mg/day to 3000 mg/day) Comparator(s): dapagliflozin (10 mg/day)
Outcomes	Primary outcome(s): time to first occurrence of a confirmed composite endpoint of death, myocardial infarction, stroke, heart failure, diabetic nephropathy, retinopathy or foot ulcer Secondary outcome(s): ordinal analysis of components of primary endpoint, time to first occurrence of a confirmed composite endpoint of death, myocardial infarction, stroke, heart failure, diabetic nephropathy, retinopathy or foot ulcer (ICD10 diagnosis codes) or initiation of insulin treatment, time to first occurrence of a confirmed composite endpoint of non‐fatal myocardial infarction, stroke, heart failure, unstable angina or cardiovascular death, time to first occurrence of a confirmed composite endpoint of heart failure or cardiovascular death, death, microvascular events, first of; occurrence or progression of retinopathy, nephropathy, diabetic foot lesions, need for insulin treatment, treatment failure, defined as add‐on or switch to another glucose‐lowering drug, change in glycemic control, LDL‐cholesterol, HDL‐cholesterol, total cholesterol, triglycerides, albuminuria, blood pressure, body weight and BMI, health care costs, health‐related quality of life, health‐related quality of life with respect to diabetes treatment satisfaction Other outcome(s): —
Starting date	Trial start date: September 2019 Trial completion date: September 2024
Contact information	Responsible party/principal investigator: Jan Eriksson, MD, Uppsala University Hospital
Study identifier	Trial identifier: NCT03982381
Official title	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
Stated purpose of study	—
Notes

—: denotes not reported

ALT: alanine aminotransferase; BMI: body mass index; GLP‐1: glucagon‐like peptide 1; HbA1c: glycated haemoglobin; HIV: human immunodeficiency virus; ICD 10: International Classification of Diseases 10th revision; LDL: low‐density lipoprotein; MEN‐2: multiple endocrine neoplasia type 2; OGTT: oral glucose tolerance test; UACR: urine albumin: creatinine ratio; UNL: upper normal limit