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

NCT03982381 | Completed Phase 4 DMC

• 2 other identifiers: SMART-20192019-001046-17
• Study Type: interventional
• Target: 2,067
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Type 2 Diabetes

Outcome Measures

Primary Outcomes (1)

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

Secondary Outcomes (20)

• Ordinal analysis of components of primary endpoint (see above)

  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.

  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.

  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.

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

• Death

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

Study Arms (2)

Metformin

ACTIVE COMPARATOR

Metformin 1000-3000 mg per day according to clinical guidelines. Split into 2-3 doses per day.

Drug: Metformin

Dapagliflozin

EXPERIMENTAL

Dapagliflozin 10 mg once daily

Drug: Dapagliflozin 10 MG

Interventions

Metformin DRUG

Active comparator

Metformin

Dapagliflozin 10 MG DRUG

Experimental treatment

Dapagliflozin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Uppsala University: lead
• Uppsala University Hospital: collaborator
• Swedish Healthcare Regions: collaborator
• National Board of Health and Welfare, Sweden: collaborator
• The Swedish National Diabetes Register: collaborator

Study Sites (1)

Uppsala University Hospital

Uppsala, 75185, Sweden

Location

Related Publications (4)

• Eriksson JW, Fanni G, Lundqvist MH, Jansson S, Radholm K, Sofizadeh S, Patsoukaki V, Nilsson A, Lindholm D, Rolandsson O, Norhammar A, Granstam E, Eliasson B, Bennet L, Sundstrom J. SGLT2 inhibitor or metformin as standard treatment in early-stage type 2 diabetes? Baseline data in SMARTEST, a novel, decentralised, register-based randomised trial on prevention of diabetic complications. Diabetes Obes Metab. 2026 Feb;28(2):1327-1338. doi: 10.1111/dom.70320. Epub 2025 Nov 28.

  PMID: 41311237 DERIVED

• El-Damanawi R, Stanley IK, Staatz C, Pascoe EM, Craig JC, Johnson DW, Mallett AJ, Hawley CM, Milanzi E, Hiemstra TF, Viecelli AK. Metformin for preventing the progression of chronic kidney disease. Cochrane Database Syst Rev. 2024 Jun 4;6(6):CD013414. doi: 10.1002/14651858.CD013414.pub2.

  PMID: 38837240 DERIVED

• Sundstrom J, Kristofi R, Ostlund O, Bennet L, Eliasson B, Jansson S, Leksell J, Almby K, Lundqvist M, Eriksson JW; SMARTEST study group (see list in Appendix). A registry-based randomised trial comparing an SGLT2 inhibitor and metformin as standard treatment of early stage type 2 diabetes (SMARTEST): Rationale, design and protocol. J Diabetes Complications. 2021 Oct;35(10):107996. doi: 10.1016/j.jdiacomp.2021.107996. Epub 2021 Jul 21.

  PMID: 34389234 DERIVED

• Gnesin F, Thuesen ACB, Kahler LKA, Madsbad S, Hemmingsen B. Metformin monotherapy for adults with type 2 diabetes mellitus. Cochrane Database Syst Rev. 2020 Jun 5;6(6):CD012906. doi: 10.1002/14651858.CD012906.pub2.

  PMID: 32501595 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

Metformin; dapagliflozin

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals

Study Officials

• Jan Eriksson, MD

  Uppsala University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: Treatment is blinded to outcome analysis team, until after database lock
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Prospective randomized, open label, blinded endpoint design (PROBE). Multicenter study.

Study Record Dates

• First Submitted: May 27, 2019
• First Posted: June 11, 2019
• Study Start: September 5, 2019
• Primary Completion: January 31, 2026
• Study Completion: January 31, 2026
• Last Updated: March 4, 2026

Record last verified: 2026-03

Data Sharing

• IPD Sharing: Will not share

Locations

SE (1)