Adipose Tissue Heterogeneity and Its Link to Type 2 Diabetes

Type 2 Diabetes Clinical Trial

— DiaSpax  

Official title:

Adipose Tissue Heterogeneity and Its Link to Type 2 Diabetes: A Randomized Open Intervention Study That Compares Empagliflozin, Pioglitazone and Semaglutide

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05501483
• Other study ID #: Karolinska University Hospital
• Secondary ID: 2021-002367-21
• Status: Recruiting
• Phase: N/A
• Start date: February 8, 2023
• Est. completion date: December 31, 2032

Study information

• Verified date: October 2023
• Source: Karolinska Institutet
• Contact: Mikael Ryden, MD, PhD
• Phone: +46736995215
• Email: mikael.ryden[@]ki.se
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 60
• Est. completion date: December 31, 2032
• Est. primary completion date: September 1, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 30 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Diabetes Mellitus
• Diabetes Mellitus, Type 2
• Type 2 Diabetes

Intervention

Drug:
• Pioglitazone 45 mg
Starts with 45 mg
• Empagliflozin 25 MG
Starts with 25 mg
• Semaglutide 7 MG
Starts with 3 mg daily for the first 2 weeks

Locations

Country	Name	City	State
Sweden	Karolinska University Hospital	Stockholm

Sponsors (2)

Lead Sponsor	Collaborator
Karolinska Institutet	Karolinska University Hospital

Country where clinical trial is conducted

Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Changes in tissue cellularity after 6 months of treatment (explorative outcome)	Changes in adipose tissue cellularity measured by single-cell transcriptomic analyses of fat tissue biopsies	Baseline and after six months intervention
Primary	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	Changes in fat cell heterogeneity after 6 months of treatment	Changes in the adiponectin/leptin mRNA expression ratio in adipose tissue measured by quantitative PCR	Baseline and after six months intervention