Adipose Tissue Heterogeneity and Its Link to Type 2 Diabetes

NCT05501483 | Recruiting DMC

• 3 other identifiers: Karolinska University Hospital2022-00792 and 2024-034342021-002367-21
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 1

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.

Conditions

Type 2 Diabetes

Outcome Measures

Primary Outcomes (1)

• Changes in fat cell lipolysis after 6 months of treatment

  Change in isoprenaline-induced (over basal) lipolysis in isolated fat cells

  Baseline and after six months intervention

Secondary Outcomes (1)

• Changes in fat cell heterogeneity after 6 months of treatment

  Baseline and after six months intervention

Other Outcomes (1)

• Changes in tissue cellularity after 6 months of treatment (explorative outcome)

  Baseline and after six months intervention

Study Arms (3)

Pioglitazone

ACTIVE COMPARATOR

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.

Drug: Pioglitazone 45 mg

Empagliflozin

EXPERIMENTAL

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

Drug: Empagliflozin 25 MG

Semaglutide

EXPERIMENTAL

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

Drug: Semaglutide 7 MG

Interventions

Pioglitazone 45 mg DRUG

Starts with 45 mg

Pioglitazone

Empagliflozin 25 MG DRUG

Starts with 25 mg

Empagliflozin

Semaglutide 7 MG DRUG

Starts with 3 mg daily for the first 2 weeks

Semaglutide

Eligibility Criteria

• Age: 30 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed informed consent
• BMI 25 kg/m2 or higher
• HbA1c 42 mmol/mol or higher
• For fertile women, effective contraception

You may not qualify if:

• 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

Sponsors & Collaborators

• Karolinska Institutet: lead
• Karolinska University Hospital: collaborator

Study Sites (1)

Karolinska University Hospital

Stockholm, 14186, Sweden

RECRUITING

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

Pioglitazone; empagliflozin; semaglutide

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Thiazolidinediones; Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Central Study Contacts

Mikael Ryden, MD, PhD

CONTACT

+46736995215; mikael.ryden@ki.se

Jesper Bäckdahl, MD, PhD

CONTACT

+46702297237; jesper.backdahl@ki.se

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor, senior consultant, MD, PhD

Model Details: Participants are recruited to either of three groups where they receive (in addition to metformin) any of the three study drugs.

Study Record Dates

• First Submitted: August 10, 2022
• First Posted: August 15, 2022
• Study Start: February 8, 2023
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): December 31, 2032
• Last Updated: February 26, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

SE (1)