Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Semaglutide and Dapagliflozin in Diabetic Patients With Different Pathophysiology

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
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

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.

Condition or disease Intervention/treatment Phase
Type2 Diabetes Drug: Semaglutide Drug: Dapagliflozin Phase 2

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.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 200 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Semaglutide and Dapagliflozin in Diabetic Patients With Different Pathophysiology
Actual Study Start Date : June 15, 2020
Estimated Primary Completion Date : July 31, 2021
Estimated Study Completion Date : December 31, 2021

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
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.
Drug: Semaglutide
Ozempic s.c. once weekly for 6 months
Other Name: Ozempic

Active Comparator: dapagliflozin
Those randomized to dapagliflozin will receive 10 mg orally once daily in addition to metformin.
Drug: Dapagliflozin
Forxiga 10 mg p.o. once daily for 6 months
Other Name: Forxiga




Primary Outcome Measures :
  1. 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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04451837


Contacts
Layout table for location contacts
Contact: Anders Rosengren 0705316704 anders.rosengren@med.lu.se

Locations
Layout table for location information
Sweden
Anders Rosengrentest Recruiting
Malmö, Skane, Sweden, 20502
Contact: Anders Rosengren, Professor    0705316704    anders.rosengren@med.lu.se   
Sponsors and Collaborators
Region Skane
Göteborg University
Investigators
Layout table for investigator information
Principal Investigator: Anders Rosengren Region Skåne
Layout table for additonal information
Responsible Party: Region Skane
ClinicalTrials.gov Identifier: NCT04451837    
Other Study ID Numbers: DIAB1
First Posted: June 30, 2020    Key Record Dates
Last Update Posted: July 2, 2020
Last Verified: June 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
2-(3-(4-ethoxybenzyl)-4-chlorophenyl)-6-hydroxymethyltetrahydro-2H-pyran-3,4,5-triol
Sodium-Glucose Transporter 2 Inhibitors
Molecular Mechanisms of Pharmacological Action
Hypoglycemic Agents
Physiological Effects of Drugs