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

Phase 1

Conditions: Diabetes type 2
MedDRA version: 20.0Level: SOCClassification code: 10027433Term: Metabolism and nutrition disorders Class: 6
MedDRA version: 21.1Level: LLTClassification code: 10045242Term: Type II diabetes mellitus Class: 10027433
MedDRA version: 20.0Level: PTClassification code: 10012601Term: Diabetes mellitus Class: 100000004861
Therapeutic area: Diseases [C] - Nutritional and Metabolic Diseases [C18]

Registration Number: CTIS2024-513416-98-00

Lead Sponsor: Karolinska University Hospital

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 60

Inclusion Criteria

The participant has provided written consent to participate in the study, Age 30-70, BMI =25, HbA1c =42 mmol/mol, Fertile women must use effective contraception throughout the study. Effective contraception includes any of the following: Combined hormonal contraceptives (estrogen and progestogen) that inhibit ovulation: oral, intravaginal, or transdermal; Progestogen-only contraceptives that inhibit ovulation: oral, injectable, or implantable; Intrauterine device (hormonal or copper); Bilateral tubal occlusion; Vasectomized partner; Sexual abstinence (refraining from heterosexual intercourse throughout the study). Women of childbearing potential need a negative pregnancy test at screening before randomization.

Exclusion Criteria

HbA1C = 65 mmol/mol, Low C-peptide/glucose ratio indicative of endogenous insulin deficiency (less than 2 measured as pmol/mg per dL), NT-proBNP 20% above the normal reference value, Kidney disease/impairment (eGFR <60 ml/min), Liver disease and/or impairment (hepatic values over twice the upper reference value), Other severe chronic illness including ongoing cancer, Established cardiovascular disease and/or heart failure, Severe psychiatric condition, Active alcoholism, Insulin treatment, Waran or NOAK-treatment, Pregnancy, nursing or planned pregnancy, Ongoing pregnancy (positive pregnancy test), Positive GAD or IA2 antibodies (Above reference range)

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: How do various antidiabetic drugs differ in their beneficial effects on adipose tissue function?;Secondary Objective: Do the studied antidiabetic drugs have different effects on the cellular composition of adipose tissue (adipose tissue heterogeneity) measured using bulk and single-cell techniques?;Primary end point(s): Lipolysis is measured as basal and maximal isoprenaline-stimulated lipolysis in isolated adipocytes from the subcutaneous abdominal periumbilical adipose tissue and expressed as log10 ISO-stimulated/basal glycerol release ex vivo

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s):The cellular heterogeneity of adipose tissue (i.e., different adipocyte subtypes) is measured using qPCR of ADIPOQ/LEP in the same adipose tissue samples from which lipolysis is measured.