Semaglutide and Dapagliflozin in Diabetic Patients With Different Pathophysiology

NCT04451837 | Active Not Recruiting Phase 2

• 1 other identifier: DIAB1
• Study Type: interventional
• Target: 200
• Locations: 1 country
• Sites: 1

Brief Summary

Current anti-diabetic treatment fails to stop the progressive course of the disease. Recent studies have revealed a surprisingly high variability in the diabetic phenotype. The investigators propose that anti-diabetic treatment should ideally target the underlying pathophysiology of each individual patient. The investigators will therefore test whether the effect of two approved anti-diabetic drugs differs between individuals at different ends of the pathophysiological spectrum: 1) patients with poor insulin secretion, here termed SIDD and 2) patients with high insulin resistance, here termed SIRD. The study may open up a new avenue for more precise treatment of diabetic patients that would be of immediate clinical relevance.

Conditions

Type2 Diabetes

Outcome Measures

Primary Outcomes (1)

• Hba1c

  The primary endpoint will be the intraindividual change of HbA1c in response to semaglutide or dapagliflozin relative to baseline in the two patient groups.

  6 months

Study Arms (2)

semaglutide

ACTIVE COMPARATOR

Patients randomized to add semaglutide (Ozempic) will receive injection training at the study site and inject 0.25 mg subcutaneously once weekly during the first four weeks, followed by 0.5 mg weekly for the subsequent four weeks and finally 1.0 mg weekly throughout the study.

Drug: Semaglutide

dapagliflozin

ACTIVE COMPARATOR

Those randomized to dapagliflozin will receive 10 mg orally once daily in addition to metformin.

Drug: Dapagliflozin

Interventions

Semaglutide DRUG

Ozempic s.c. once weekly for 6 months

Also known as: Ozempic

semaglutide

Dapagliflozin DRUG

Forxiga 10 mg p.o. once daily for 6 months

Also known as: Forxiga

dapagliflozin

Eligibility Criteria

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

You may qualify if:

• Diabetes mellitus based on prior documentation or treatment with anti-hyperglycemic medication or diagnosed according to the WHO criteria (random plasma glucose \>11.1 mmol/L or fasting glucose \>7.0 mmol/L or HbA1C ≥6.5%) and disease characteristics typical for SIDD or SIRD according to the ANDIS clustering
• Ongoing metformin therapy with constant dose the last three months
• Age 18 years or above
• HbA1c ≥42 and \<91 mmol/mol
• Women who are not postmenopausal and who have not undergone surgical sterilization must have no current pregnancy, which will be assessed by pregnancy test, must take precautions to avoid pregnancy throughout the study and for 4 weeks after intake of the last dose and must be willing to use highly effective birth control methods. Methods that can achieve a failure rate of less than 1% per year when used consistently and correctly are considered as highly effective birth control methods.
• Willingness to take injectable and oral medication
• Written informed consent

You may not qualify if:

• Type 1 diabetes, LADA, MODY, secondary diabetes or history of diabetic ketoacidosis
• Anti-diabetic treatment other than metformin within 90 days prior to randomization or changed metformin dose within 90 days prior to randomization
• Known acute cardiovascular event, e.g. transient ischemic attack, stroke, acute coronary syndrome, decompensated heart failure, coronary by-pass surgery or other coronary vessel intervention within 90 days prior to screening.
• Heart failure NYHA class IV
• History of acute or chronic pancreatitis
• Known liver cirrhosis
• Blood pressure above 170/110 mm Hg
• A level of aspartate aminotransferase (ASAT) or alanine aminotransferase (ALAT), ALP or bilirubin of more than three times the upper limit of the normal range
• Current chronic daily treatment with an oral steroid at a dose equivalent to oral prednisolone ≥10 mg (e.g., betamethasone ≥1.2 mg, dexamethasone ≥1.5 mg, hydrocortisone ≥40 mg)
• Pregnancy or breast-feeding
• Known galactose intolerance, total lactase deficiency or glucose-galactose malabsorption.
• Estimated glomerular filtration rate \<45 ml/min/1,73 m2 or unstable or rapidly progressing renal disease
• Participant unable to understand the study information herself or himself
• Involvement in the planning and/or conduct of the study
• Participation in other clinical trial which may affect the outcome of the present study

Sponsors & Collaborators

• Region Skane: lead
• Göteborg University: collaborator

Study Sites (1)

Anders Rosengrentest

Malmo, Skåne County, 20502, Sweden

Location

Related Publications (1)

• Dwibedi C, Ekstrom O, Brandt J, Adiels M, Franzen S, Abrahamsson B, Rosengren AH. Randomized open-label trial of semaglutide and dapagliflozin in patients with type 2 diabetes of different pathophysiology. Nat Metab. 2024 Jan;6(1):50-60. doi: 10.1038/s42255-023-00943-3. Epub 2024 Jan 4.

  PMID: 38177805 DERIVED

MeSH Terms

Interventions

semaglutide; dapagliflozin

Study Officials

• Anders Rosengren

  Region Skåne

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 25, 2020
• First Posted: June 30, 2020
• Study Start: September 10, 2020
• Primary Completion: December 15, 2021
• Study Completion (Estimated): December 31, 2026
• Last Updated: July 16, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will not share

Locations

SE (1)