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

Phase 4Active Not RecruitingNCT03982381

Uppsala University2,067 enrolled

Overview

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)

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

SINGLE

Enrollment

2,067

Conditions

Type 2 Diabetes

Interventions

MetforminDRUG

Active comparator

Dapagliflozin 10 MGDRUG

Experimental treatment

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

Locations (1)

Uppsala University Hospital

Uppsala, Sweden

Outcomes

Primary Outcomes

Time to first occurence of a confirmed composite endpoint of death, myocardial infarction, stroke, heart failure, diabetic nephropathy, retinopathy or foot ulcer.

A confirmed composite endpoint includes death, myocardial infarction, stroke, heart failure, diabetic nephropathy, retinopathy or foot ulcer (ICD10 diagnosis codes)

Time frame: Time to first event during study period (for each patient 24-48 months, mean 36 months )

Secondary Outcomes

Ordinal analysis of components of primary endpoint (see above)

Death, major adverse cardiovascular event or microvascular event at 2 years follow-up (ICD10 diagnosis codes), scored according to severity as specified in statistical analysis plan.

Time frame: Events of any of above having occurred during 48 months following randomization.

Time to first occurence 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.

A confirmed composite endpoint includes death, myocardial infarction, stroke, heart failure, diabetic nephropathy, retinopathy or foot ulcer (ICD10 diagnosis codes) or initiation of insulin treatment (filled prescription according to Swedish Prescribed Drug Register)

Time frame: Time to first event during study period (for each patient 24-48 months, mean 36 months )

Time to first occurence of a confirmed composite endpoint of non-fatal myocardial infarction, stroke, heart failure, unstable angina or cardiovascular death.

A confirmed composite endpoint includes non-fatal myocardial infarction, stroke, heart failure, unstable angina or cardiovascular death (ICD10 diagnosis codes).

Time frame: Time to first event during study period (for each patient 24-48 months, mean 36 months )

Time to first occurence of a confirmed composite endpoint of heart failure or cardiovascular death.

Data from ClinicalTrials.gov

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A confirmed composite endpoint includes heart failure or cardiovascular death (ICD10 diagnosis codes)

Time frame: Time to first event during study period (for each patient 24-48 months, mean 36 months )

Death

Time to death (Population Register data)

Time frame: Time to event during study period (for each patient 24-48 months, mean 36 months)

Microvascular events, first of; occurrence or progression of retinopathy, nephropathy, diabetic foot lesions

Time to first event of: occurrence or progression of retinopathy, nephropathy, diabetic foot ulcers (ICD10 diagnosis codes)

Time frame: Time to first event during study period (for each patient 24-48 months, mean 36 months )

Need for insulin treatment

Time to initiation of insulin treatment (filled prescription according to Swedish Prescribed Drug Register)

Time frame: Time to first event during study period (for each patient 24-48 months, mean 36 months )

Treatment failure, defined as add-on or switch to another glucose-lowering drug

Time to event of: add-on or switch to another glucose-lowering drug (filled prescription according to Swedish Prescribed Drug Register)

Time frame: Time to first event during study period (for each patient 24-48 months, mean 36 months )

Change in glycemic control

HbA1c level (mmol/mol)

Time frame: Change during study period, at 12, 24, 36 and 48 months

Change in LDL-cholesterol

Change in LDL cholesterol from baseline (mmol/L)