Adipose Tissue Heterogeneity and Its Link to Type 2 Diabetes (DiaSpax)

Karolinska Institute

Status: Enrolling

Conditions: Type 2 Diabetes

Treatments: Drug: Pioglitazone 45 mg; Drug: Semaglutide 7 MG; Drug: Empagliflozin 25 MG

Study type: Interventional

Funder types: Other

Identifiers

NCT05501483

2021-002367-21 (EudraCT Number)

Karolinska University Hospital

Details and patient eligibility

About

People with newly diagnosed type 2 diabetes treated with metformin that have not reached their HbA1c target (49-64 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.

Full description

A detailed description of the protocol has been approved by the Swedish Medical Products Agency and the study is registered as EudraCT: 2021-002367-21.

Enrollment: 60 estimated patients

Sex: All

Ages: 30 to 65 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Signed informed consent
• BMI 27-35 kg/m2
• HbA1c 48 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

60 participants in 3 patient groups

Pioglitazone

Active Comparator group

Description:

Pioglitazone is known to affect fat cells and is used as an active comparator. It reduces HbA1c but increase fat mass slightly. We hypothesize that pioglitazone may have particular benefits in individuals with a specific adipose cellularity.

Treatment:

Drug: Pioglitazone 45 mg

Empagliflozin

Experimental group

Description:

Empagliflozin reduces HbA1c and increase lipolysis possibly due to increased glucagon secretion. It also reduces fat mass weight to a minor degree.

Treatment:

Drug: Empagliflozin 25 MG

Semaglutide

Experimental group

Description:

Semaglutide reduces body weight, including fat mass, to a more significant degree than empagliflozin but has no known direct effects on adipose tissue.

Treatment:

Drug: Semaglutide 7 MG