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Semaglutide and Dapagliflozin in Diabetic Patients With Different Pathophysiology

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ClinicalTrials.gov Identifier: NCT04451837
Recruitment Status : Recruiting
First Posted : June 30, 2020
Last Update Posted : July 2, 2020
Sponsor:
Collaborator:
Göteborg University
Information provided by (Responsible Party):
Region Skane

Tracking Information
First Submitted Date  ICMJE June 25, 2020
First Posted Date  ICMJE June 30, 2020
Last Update Posted Date July 2, 2020
Actual Study Start Date  ICMJE June 15, 2020
Estimated Primary Completion Date July 31, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 25, 2020)
Hba1c [ Time Frame: 6 months ]
The primary endpoint will be the intraindividual change of HbA1c in response to semaglutide or dapagliflozin relative to baseline in the two patient groups.
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Semaglutide and Dapagliflozin in Diabetic Patients With Different Pathophysiology
Official Title  ICMJE Semaglutide and Dapagliflozin in Diabetic Patients With Different Pathophysiology
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.
Detailed Description

The trial is a clinical phase II study that will be randomized and open-label with fixed stratification variables (SIDD and SIRD) to analyze if the response to anti-diabetic drugs differs between patients with distinct pathophysiology, as captured by SIDD and SIRD. The compounds used are semaglutide and dapagliflozin, which will be randomized to patients of each subgroup using a parallel group design.

The clusters (SIDD and SIRD) will be used as a practical tool to distinguish individuals who are at different ends of the pathophysiological spectrum.

The investigators will recruit 200 patients from the ANDIS registry with HbA1c ≥48 mmol/mol on metformin monotherapy. Half of them will have SIDD and half will have SIRD characteristics. The patients will be randomized (open-label) to receive semaglutide or dapagliflozin for six months in addition to metformin.

The investigators will recruit participants on metformin monotherapy with stable dose for the last three months. Metformin dose at inclusion (as prescribed by their regular physician) is maintained throughout the study; the investigatorswill correct for metformin dose in the analyses. Patients randomized to add semaglutide 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. Those randomized to dapagliflozin will receive 10 mg orally once daily in addition to metformin. The participants will attend a screening visit followed by three study visits at 0, 3, 6 months. At the first and last study visit they will undergo an OGTT. HbA1c will be measured at all study visits.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Type2 Diabetes
Intervention  ICMJE
  • Drug: Semaglutide
    Ozempic s.c. once weekly for 6 months
    Other Name: Ozempic
  • Drug: Dapagliflozin
    Forxiga 10 mg p.o. once daily for 6 months
    Other Name: Forxiga
Study Arms  ICMJE
  • Active Comparator: semaglutide
    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.
    Intervention: Drug: Semaglutide
  • Active Comparator: dapagliflozin
    Those randomized to dapagliflozin will receive 10 mg orally once daily in addition to metformin.
    Intervention: Drug: Dapagliflozin
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: June 25, 2020)
200
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 31, 2021
Estimated Primary Completion Date July 31, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • • 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 ≥48 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

Exclusion Criteria:

  • • 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
    • Any condition or treatment that in the judgment of the investigator makes it difficult or unsafe to participate in the study
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Anders Rosengren 0705316704 anders.rosengren@med.lu.se
Listed Location Countries  ICMJE Sweden
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04451837
Other Study ID Numbers  ICMJE DIAB1
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Region Skane
Study Sponsor  ICMJE Region Skane
Collaborators  ICMJE Göteborg University
Investigators  ICMJE
Principal Investigator: Anders Rosengren Region Skåne
PRS Account Region Skane
Verification Date June 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP