Adipose Tissue Heterogeneity and Its Link to Type 2 Diabetes

Not Applicable

Recruiting

• Conditions: Type 2 Diabetes
• Interventions: Drug: Pioglitazone 45 mg; Drug: Semaglutide 7 MG; Drug: Empagliflozin 25 MG

• Registration Number: NCT05501483
• Lead Sponsor: Karolinska Institutet

Brief Summary

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.

Detailed 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.

Study Timeline

• Study First Submitted: 2022-08-10
• Study First Submitted QC: 2022-08-11
• Study First Posted: 2022-08-15
• Study Start: 2023-02-08
• Status Verified: 2025-02
• Last Update Submitted: 2025-02-24
• Last Update Posted: 2025-02-26
• Primary Completion: 2026-09-01
• Study Completion: 2032-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 60

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Pioglitazone	Pioglitazone 45 mg	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.
Semaglutide	Semaglutide 7 MG	Semaglutide reduces body weight, including fat mass, to a more significant degree than empagliflozin but has no known direct effects on adipose tissue.
Empagliflozin	Empagliflozin 25 MG	Empagliflozin reduces HbA1c and increase lipolysis possibly due to increased glucagon secretion. It also reduces fat mass weight to a minor degree.

Primary Outcome Measures

Name	Time	Method
Changes in fat cell lipolysis after 6 months of treatment	Baseline and after six months intervention	Change in isoprenaline-induced (over basal) lipolysis in isolated fat cells

Secondary Outcome Measures

Name	Time	Method
Changes in fat cell heterogeneity after 6 months of treatment	Baseline and after six months intervention	Changes in the adiponectin/leptin mRNA expression ratio in adipose tissue measured by quantitative PCR

Trial Locations

Locations (1)

Karolinska University Hospital; 🇸🇪 Stockholm, Sweden