Semaglutide and Dapagliflozin in Diabetic Patients With Different Pathophysiology

• Status: Active, not recruiting
• Trial end date: 2021-12-31
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Region Skane
• Collaborator: Göteborg University
• Treatments: 2-(3-(4-ethoxybenzyl)-4-chlorophenyl)-6-hydroxymethyltetrahydro-2H-pyran-3,4,5-triol; Dapagliflozin

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