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

NCT04662866 | Unknown Phase 2 DMC

• 1 other identifier: 24993
• Study Type: interventional
• Target: 64
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Impaired Glucose Tolerance; Insulin Sensitivity; Glucose Metabolism Disorders

Outcome Measures

Primary Outcomes (1)

• Endogenous glucose production during fasting

  Difference between treatment arms in change from baseline to 12 weeks in endogenous glucose production during fasting measured by the deuterated glucose tracer dilution method in umol/(kg fat free mass x minutes)

  After 12 weeks on respective drugs

Other Outcomes (7)

• Endogenous glucose production during hyperinsulinemia

  After 12 weeks on respective drugs

• Whole body insulin sensitivity

  After 12 weeks on respective drugs

• Insulin secretion

  After 12 weeks on respective drugs

Study Arms (4)

Metformin

ACTIVE COMPARATOR

Metformin 500 mg x 1, morning, for 2 weeks, then Metformin 500 mg x 2, morning and evening for 10 weeks.

Drug: Metformin capsule 500 mg, Empagliflozin encapsulated tablet 10 mg, Pioglitazone encapsulated tablet 30 mg, Linagliptin encapsulated tablet 5 mg

Empagliflozin

ACTIVE COMPARATOR

Empagliflozin 10 mg x 1, morning, for 2 weeks, then Empagliflozin 10 mg morning + Placebo evening for 10 weeks.

Drug: Metformin capsule 500 mg, Empagliflozin encapsulated tablet 10 mg, Pioglitazone encapsulated tablet 30 mg, Linagliptin encapsulated tablet 5 mg

Linagliptin

ACTIVE COMPARATOR

Linagliptin 5 mg x 1, morning, for 2 weeks, then Linagliptin 5 mg morning + Placebo evening for 10 weeks.

Drug: Metformin capsule 500 mg, Empagliflozin encapsulated tablet 10 mg, Pioglitazone encapsulated tablet 30 mg, Linagliptin encapsulated tablet 5 mg

Pioglitazone

ACTIVE COMPARATOR

Pioglitazone 30 mg x 1, morning, for 2 weeks, then Pioglitazone 30 mg morning + Placebo evening for 10 weeks.

Drug: Metformin capsule 500 mg, Empagliflozin encapsulated tablet 10 mg, Pioglitazone encapsulated tablet 30 mg, Linagliptin encapsulated tablet 5 mg

Interventions

Metformin capsule 500 mg, Empagliflozin encapsulated tablet 10 mg, Pioglitazone encapsulated tablet 30 mg, Linagliptin encapsulated tablet 5 mg DRUG

Comparison of 4 different antihyperglycemic drugs

Also known as: biguanide, glitazone, sodium glucose transport inhibitor, dipeptidyl peptidase inhibitor

Empagliflozin; Linagliptin; Metformin; Pioglitazone

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Able and willing to give informed consent
• Woman ≥ 18 years of age
• Of South Asian origin
• 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

You may not qualify if:

• Known type 2 diabetes
• Known type 1 diabetes
• Pregnant or fully lactating at randomisation or planned during study period.
• 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.
• Concomitant use of any antidiabetic medication
• Concomitant use of fibrates or rifampicin
• Radiological examinations iodine containing contrast the previous week before randomisation, or planned during the study period.
• Known serious illness such as cancer (except in situ carcinoma) during past 5 years.
• Previous radiation therapy directed towards the pelvic area.
• Heart failure New York Heart Association (NYHA) class I-IV.
• Estimated glomerulus filtration rate (eGFR) \< 60 ml/min/1,73m2
• 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.
• Hypothyroidism where substitution with levothyroxine has not been stable for the last 3 months or with thyroid stimulating hormone (TSH) outside normal limits.
• A history of bullous pemphigoid
• A history of acute or chronic pancreatitis

Sponsors & Collaborators

• Oslo University Hospital: lead
• The Research Council of Norway: collaborator
• Norwegian Diabetes Association: collaborator
• South-Eastern Norway Regional Health Authority: collaborator
• University of Oslo: collaborator
• University Hospital, Akershus: collaborator
• Vestre Viken Hospital Trust: collaborator
• University of Glasgow: collaborator

Study Sites (1)

Oslo University Hospital, Aker Hospital

Oslo, 0424, Nydalen, Norway

RECRUITING

MeSH Terms

Conditions

Glucose Intolerance; Insulin Resistance; Glucose Metabolism Disorders

Interventions

Metformin; Biguanides; Thiazolidinediones

Condition Hierarchy (Ancestors)

Hyperglycemia; Metabolic Diseases; Nutritional and Metabolic Diseases; Hyperinsulinism

Intervention Hierarchy (Ancestors)

Guanidines; Amidines; Organic Chemicals; Thiazoles; Sulfur Compounds; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Kåre I Birkeland, MD, PhD

  Professor

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Anita Suntharalingam, MD

CONTACT

+4722894745; ansunt@ous-hf.no

Ellen Hillestad, Pharm.techn.

CONTACT

+4722894000; elhill@ous-hf.no

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Blinded medication
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor

Model Details: Randomised controlled trial (RCT), 4 parallel groups

Study Record Dates

• First Submitted: November 16, 2020
• First Posted: December 10, 2020
• Study Start: February 10, 2021
• Primary Completion: December 1, 2022
• Study Completion: October 1, 2023
• Last Updated: April 8, 2021

Record last verified: 2021-04

Locations

NO (1)