Type 2 Diabetes
Conditions
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.
Interventions
Starts with 45 mg
DRUGEmpagliflozin 25 MG
Starts with 25 mg
DRUGSemaglutide 7 MG
Starts with 3 mg daily for the first 2 weeks
Sponsors
Karolinska University Hospital
Karolinska Institutet
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Participants are recruited to either of three groups where they receive (in addition to metformin) any of the three study drugs.
Eligibility
Sex/Gender
ALL
Age
30 Years to 70 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
Other
| Measure | Time frame | Description |
|---|---|---|
| Changes in tissue cellularity after 6 months of treatment (explorative outcome) | Baseline and after six months intervention | Changes in adipose tissue cellularity measured by single-cell transcriptomic analyses of fat tissue biopsies |
Countries
Sweden
Contacts
Primary ContactMikael Ryden, MD, PhD
Backup ContactJesper Bäckdahl, MD, PhD
Outcome results
None listed