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

NCT ID: NCT03982381

Last Updated: 2024-12-09

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE4

Total Enrollment

2067 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-09-05

Study Completion Date

2025-10-15

Brief Summary

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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.

Detailed Description

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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)

Conditions

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Type 2 Diabetes

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Prospective randomized, open label, blinded endpoint design (PROBE). Multicenter study.
Primary Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Outcome Assessors
Treatment is blinded to outcome analysis team, until after database lock

Study Groups

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Metformin

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

Group Type ACTIVE_COMPARATOR

Metformin

Intervention Type DRUG

Active comparator

Dapagliflozin

Dapagliflozin 10 mg once daily

Group Type EXPERIMENTAL

Dapagliflozin 10 MG

Intervention Type DRUG

Experimental treatment

Interventions

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Metformin

Active comparator

Intervention Type DRUG

Dapagliflozin 10 MG

Experimental treatment

Intervention Type DRUG

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Uppsala University Hospital

OTHER

Sponsor Role collaborator

Swedish Healthcare Regions

UNKNOWN

Sponsor Role collaborator

National Board of Health and Welfare, Sweden

OTHER_GOV

Sponsor Role collaborator

The Swedish National Diabetes Register

UNKNOWN

Sponsor Role collaborator

Uppsala University

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Jan Eriksson, MD

Role: PRINCIPAL_INVESTIGATOR

Uppsala University

Locations

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Uppsala University Hospital

Uppsala, , Sweden

Site Status

Countries

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Sweden

References

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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.

Reference Type DERIVED
PMID: 38837240 (View on PubMed)

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.

Reference Type DERIVED
PMID: 34389234 (View on PubMed)

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.

Reference Type DERIVED
PMID: 32501595 (View on PubMed)

Other Identifiers

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2019-001046-17

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

SMART-2019

Identifier Type: -

Identifier Source: org_study_id