Type 2 Diabetes MedDRA version: 21.1 Level: LLT Classification code 10045242 Term: Type II diabetes mellitus System Organ Class: 100000004861
Conditions
Interventions
Trade Name: Forxiga
Pharmaceutical Form: Coated tablet
INN or Proposed INN: Dapagliflozin
CAS Number: 461432-26-8
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 10
Sponsors
Uppsala University
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Diagnosis of T2D (according to WHO criteria) with less than 4 years duration. 2. Men and women, age > 18 years 3. BMI 18.5 - 45 kg/m2 4. Medication for type 2 diabetes: a) drug naïve, or newly started or short temporary medication* b) ongoing or previous monotherapy with oral GLD medication for more than 4 weeks in total** 5. Participation in the Swedish National Diabetes Register (NDR) and accepting individual data collection from this register and those of SoS/SCB. 6. Signed informed consent *Stratum A: no GLD treatment, except for any ongoing or previous treatment for maximally 4 weeks in total. **Stratum B. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 1200 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 1000
Exclusion criteria
Exclusion criteria: Subjects will not be included in the study if any of the following exclusion criteria apply: 1. Known or suspected other form of diabetes than type 2 2. Ongoing or >4 weeks in total of any previous treatment for type 2 diabetes with: insulin, GLP-1 receptor agonists, SGLT2 inhibitors or combination of any diabetes medications 3. Medical need for any specific GLD treatment, eg. insulin due to marked hyperglycemia 4. HbA1c >70 mmol/mol for patients on monotherapy. >80 in drug naïve, but a higher HbA1c can be accepted if the current glucose levels imply a rapid trajectory towards acceptable glucose control 5. Contraindication to either metformin or dapagliflozin, or any unacceptable risk with either treatment as assessed by the investigator 6. History of established cardiovascular disease: diagnosis of myocardial infarction, angina pectoris, stroke, lower ex¬tremity arterial disease, heart failure or ongoing diabetic foot ulcers. 7. Any serious illness or other condition with short life expectancy (<4 yr) 8. Renal impairment (eGFR <60 ml/min/1,73m2) 9. 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. For example, serious psychiatric or alcohol or substance abuse disorders. 10. 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 11. Involvement in the planning and/or conduct of the study 12. Ongoing participation in another clinical trial
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To determine whether SGLT2-inhibitor treatment, as compared to metformin, is beneficial in patients with early T2D in promoting progression-free survival;Secondary Objective: Efficacy: To determine whether SGLT2 inhibitor treatment, as compared to metformin, is beneficial in early T2D in promoting progression-free survival when severity of events are taken into account. Efficacy: To determine whether SGLT2 inhibitor treatment, as compared to metformin, is beneficial in early T2D in promoting progression-free survival including delay in need for insulin treatment. Safety: To determine whether SGLT2i and metformin treatment in patients with early T2D differ with respect to serious adverse events (SAEs). Safety: To determine whether SGLT2i and metformin treatment in patients with early T2D differ with respect to diabetes-specific SAEs;Primary end point(s): Time to first of: 1. All-cause death 2. Major adverse cardiovascular events (MACE; myocardial infarction, stroke, heart failure) 3. Microvascular events (occurrence or progression of retinopathy, nephropathy, or diabetic foot lesions);Timepoint(s) of evaluation of this end point: At time of event | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Modified composite endpoint with weighted components 1-3 of primary endpoint based on their individual degrees of severity (falling in that order). Ordinal analysis at 2 years of follow-up. Time to first event among: individual components of the primary endpoint or initiation of insulin treatment. Time to first of: non-fatal myocardial infarction, stroke, heart failure, unstable angina or cardiovascular death Time to first of: heart failure or cardiovascular death Time to event of death Time to first microvascular event; occurrence or progression of retinopathy, nephropathy, diabetic foot lesions Time to initiation of insulin treatment Time to any treatment failure, defined as add-on or switch to another GLD Change in: 1) HbA1c 2) total cholesterol 3) LDL- cholesterol 4) HDL-cholesterol 5) Triglycerides 6) Urinary albumin/creatinine ratio 7) BMI 8) Systolic blood pressure 9) Diastolic blood pressure Diagnosis-based (IDG) costs for all health care during study period plus medication cost Results from RAND-36 and DTSQ questionnaires. Occurrence of SAEs (all non-elective hospitalisations or other SAEs). Occurrence of diabetes- and treatment-specific SAEs (hospitalisations for diabetes, severe hypoglycaemia, ketoacidosis, lactate acidosis, diabetic coma, amputations, fractures).;Timepoint(s) of evaluation of this end point: Time to event/time to SAE At end of study for continuous variables At specified timepoints (0-2 years after randomization) for RAND-36 and DTSQ | — |
Countries
Sweden
Contacts
Public ContactJan Eriksson
Uppsala University
Outcome results
None listed