RECRUITINGINTERVENTIONAL

Adipose Tissue Heterogeneity and Its Link to Type 2 Diabetes

Adipose Tissue Heterogeneity and Its Link to Type 2 Diabetes: A Randomized Open Intervention Study That Compares Empagliflozin, Pioglitazone and Semaglutide

About This Trial

People with newly diagnosed type 2 diabetes treated with metformin that have not reached their HbA1c target (42-64 mmol/mol) will be recruited to the study. If they fulfill the inclusion and none of the exclusion criteria, they will be, after signing informed consent, randomized to a six-month intervention with either pioglitazone, empagliflozin or semaglutide. Fat biopsies are obtained from the subcutaneous abdominal area before and after a hyperinsulinemic-euglycemic clamp at baseline and after six months. Participants are regularly followed during this the intervention. The overall goal is to determine how antidiabetic-drugs affect white adipose tissue cellularity and whether adipose heterogeneity impacts on drug response. The primary outcome measure is the change in fat tissue lipolysis (glycerol release in isolated fat cells after hormone stimulation) before and after treatment.

Who May Be Eligible (Plain English)

Who May Qualify: - Signed willing to sign a consent form - BMI 25 kg/m2 or higher - HbA1c 42 mmol/mol or higher - For fertile women, effective contraception Who Should NOT Join This Trial: - HbA1c 65 mmol/mol or higher - Established cardiovascular disease and/or heart failure - Severe psychiatric condition - Active alcoholism - Insulin treatment - Anticoagulant therapy (vitamin K antagonists or equivalent) - Pregnancy, lactation - Positive GAD or IA2 antibodies - Low C-peptide/glucose ratio (less than 2 measured as pmol/mg per dL) - NT-proBNP above the upper normal reference value - Kidney disease - Liver disease or hepatic values over twice the upper reference value - Severe concomitant disease including ongoing cancer Always talk to your doctor about whether this trial is right for you.

Original Eligibility Criteria

View original clinical language

Inclusion Criteria: * Signed informed consent * BMI 25 kg/m2 or higher * HbA1c 42 mmol/mol or higher * For fertile women, effective contraception Exclusion Criteria: * HbA1c 65 mmol/mol or higher * Established cardiovascular disease and/or heart failure * Severe psychiatric condition * Active alcoholism * Insulin treatment * Anticoagulant therapy (vitamin K antagonists or equivalent) * Pregnancy, lactation * Positive GAD or IA2 antibodies * Low C-peptide/glucose ratio (less than 2 measured as pmol/mg per dL) * NT-proBNP above the upper normal reference value * Kidney disease * Liver disease or hepatic values over twice the upper reference value * Severe concomitant disease including ongoing cancer

Treatments Being Tested

DRUG

Pioglitazone 45 mg

Starts with 45 mg

DRUG

Empagliflozin 25 MG

Starts with 25 mg

DRUG

Semaglutide 7 MG

Starts with 3 mg daily for the first 2 weeks

Locations (1)

Karolinska University Hospital

Stockholm, Sweden