SGLT2 inhibitor or metformin as standard treatment in early type 2 diabetes (SMARTEST)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Uppsala University

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Nutritional and Metabolic Diseases [C18]

Decision date (initial)

2024-08-30

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Regional Funding · Uppsala University · Ögonfonden · Swedish Research Council · ALF

External identifiers

EU CT number

2024-516228-33-00

EudraCT number

2019-001046-17

ClinicalTrials.gov

NCT03982381

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

To determine whether SGLT2-inhibitor treatment, as compared to metformin, is beneficial in patients with early T2D in promoting progression-free survival

Secondary objectives 4

1. 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.
2. 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.
3. Safety: To determine whether SGLT2i and metformin treatment in patients with early T2D differ with respect to serious adverse events (SAEs).
4. Safety: To determine whether SGLT2i and metformin treatment in patients with early T2D differ with respect to diabetes-specific SAEs

Conditions and MedDRA coding

Type 2 Diabetes

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

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 (Stratum A: no GLD treatment, except for any ongoing or previous treatment for maximally 4 weeks in total) b) ongoing or previous monotherapy with oral GLD medication for more than 4 weeks in total (Stratum B).
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

Exclusion criteria 12

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 extremity 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

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 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)

Secondary endpoints 12

1. 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.
2. Time to first event among: individual components of the primary endpoint or initiation of insulin treatment.
3. Time to first of: non-fatal myocardial infarction, stroke, heart failure, unstable angina or cardiovascular death
4. Time to first of: heart failure or cardiovascular death Time to event of death
5. Time to first microvascular event; occurrence or progression of retinopathy, nephropathy, diabetic foot lesions
6. Time to initiation of insulin treatment
7. Time to any treatment failure, defined as add-on or switch to another GLD
8. 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
9. Diagnosis-based (IDG) costs for all health care during study period plus medication cost
10. Results from RAND-36 and DTSQ questionnaires, 0-2 years after randomization.
11. Occurrence of SAEs (all non-elective hospitalisations or other SAEs).
12. Occurrence of diabetes- and treatment-specific SAEs (hospitalisations for diabetes, severe hypoglycaemia, ketoacidosis, lactate acidosis, diabetic coma, amputations, fractures).

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Comparator 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Uppsala University

Sponsor organisation

Uppsala University

Address

Box 256

City

Uppsala

Postcode

751 05

Country

Sweden

Scientific contact point

Organisation

Uppsala University

Contact name

Dept of Medical Sciences, Clinical Diabetes and Metabolism

Public contact point

Organisation

Uppsala University

Contact name

Dept of Medical Sciences, Clinical Diabetes and Metabolism

Locations

1 EU/EEA country · 35 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 6 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications