Effects of Glucose Lowering Agents in South Asian Women With Impaired Glucose Tolerance or Impaired Fasting Glucose

• Status: Recruiting
• Trial end date: 2023-10-01
• Target enrollment: 0
• Participant gender: Female

Summary

This study will test the effect of four common oral anti-diabetic agents on hepatic insulin sensitivity in South Asian women with impaired glucose tolerance or impaired fasting glucose. In a 12-week, double-blind, randomized controlled intervention trial, the following drugs will be tested head-to-head: Metformin, Pioglitazone, Empagliflozin and Linagliptin. Additional, exploratory outcomes include whole body insulin sensitivity, insulin secretion and other markers of glucose and lipid metabolism, measured by the euglycemic clamp with stable isotope tracer dilution, indirect calorimetry and CT-measurements of abdominal adipose tissue compartment volumes and hepatic and pancreatic volume and attenuation.

The study is part of the DIASA - DIAbetes in South Asians - Research Programme, which aims to find ways to improve both prevention and treatment of type 2 diabetes in people of South Asian ethnicity.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Oslo University Hospital
• Collaborators: Norwegian Diabetes Association; South-Eastern Norway Regional Health Authority; The Research Council of Norway; University Hospital, Akershus; University of Glasgow; University of Oslo; Vestre Viken Hospital Trust
• Treatments: Biguanides; Empagliflozin; Linagliptin; Metformin; Pioglitazone; Protease Inhibitors

Criteria

Inclusion Criteria:

1. Able and willing to give informed consent

2. Woman ≥ 18 years of age

3. Of South Asian origin

4. Participated in the DIASA 1 study (i.e. has had previous gestational diabetes (GDM) in last pregnancy). A period of 3 months after the 3-year limit since childbirth after GDM is seen as acceptable for inclusion.

5. Impaired glucose tolerance (2-hour glucose value ≥7.8 and < 11.1 mmol/l) and/or impaired fasting glucose (fasting plasma glucose ≥ 6.1 and < 7.0 mmol/l) diagnosed in DIASA 1

Exclusion Criteria:

1. Known type 2 diabetes

2. Known type 1 diabetes

3. Fasting or 2-hour glucose values outside the inclusion criteria if the subject according to protocol needs to undergo an OGTT at baseline in DIASA 3

4. Pregnant or fully lactating at randomisation or planned during study period.

5. Not willing to practice a highly effective birth control method* prior to initial dose, during study and for 2 weeks after the last administration of study drug.

6. Concomitant use of any antidiabetic medication

7. Concomitant use of fibrates or rifampicin

8. Radiological examinations iodine containing contrast the previous week before randomisation, or planned during the study period.

9. Known serious illness such as cancer (except in situ carcinoma) during past 5 years.

10. Previous radiation therapy directed towards the pelvic area.

11. Heart failure New York Heart Association (NYHA) class I-IV.

12. Estimated glomerulus filtration rate (eGFR) < 60 ml/min/1,73m2

13. Chronic liver disease with serum levels of aspartate aminotransferase (ASAT) or alanine amino transferase (ALAT) > 5 x upper limit of normal (ULN) or known impaired liver function (INR > 1.5, Albumin < 20 g/l, Bilirubin > 20 g/l.

14. Active infectious disease at inclusion

15. Use of systemic corticosteroids > 14 days within last 3 months before inclusion

16. Hypothyroidism where substitution with levothyroxine has not been stable for the last 3 months or with thyroid stimulating hormone (TSH) outside normal limits.

17. A history of bullous pemphigoid

18. A history of acute or chronic pancreatitis

19. Previous or present acute metabolic acidosis.

20. Known hypersensitivity to any of the active ingredients or additives in the study medication or placebo capsules.

21. Macroscopic haematuria not previously examined

22. History of major surgical procedures within 3 months prior to inclusion or planned during study period.

23. Any condition which in the investigator's opinion would jeopardize the subject's safety or compliance with the protocol.

• Birth control methods which may be considered as highly effective: Methods that can achieve a failure rate of less than 1% per year when used consistently and correctly are considered as highly effective birth control methods. Such methods include: combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation (oral, intravaginal or transdermal), progestogen-only hormonal contraception associated with inhibition of ovulation (oral, injectable or implantable), intrauterine device (IUD), intrauterine hormone-releasing system ( IUS), bilateral tubal occlusion, vasectomized partner or sexual abstinence.