Clinical trial NCT05501483: Adipose Tissue Heterogeneity and Its Link to Type 2 Diabetes
Official title: Adipose Tissue Heterogeneity and Its Link to Type 2 Diabetes: A Randomized Open Intervention Study That Compares Empagliflozin, Pioglitazone and Semaglutide
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Type 2 Diabetes
Lead sponsor: Karolinska Institutet
Sponsor class: OTHER
Collaborators: name: Karolinska University Hospital
First posted: 2022-08-15
Enrollment: 60
Sex: ALL
Minimum age (years): 30
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Participants are recruited to either of three groups where they receive (in addition to metformin) any of the three study drugs.
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Changes in fat cell lipolysis after 6 months of treatment
timeFrame: Baseline and after six months intervention
Secondary outcomes:
measure: Changes in fat cell heterogeneity after 6 months of treatment
timeFrame: Baseline and after six months intervention
Other outcomes:
measure: Changes in tissue cellularity after 6 months of treatment (explorative outcome)
timeFrame: Baseline and after six months intervention
Locations:
city: Stockholm
country: Sweden
facility: Karolinska University Hospital
Study officials:
References: