Impaired Glucose TolerancePhase 2DIASA3NCT04662866
Effects of Glucose Lowering Agents in South Asian Women With Impaired Glucose Tolerance or Impaired Fasting Glucose
A Phase 2 study testing Metformin capsule 500 mg, Empagliflozin encapsulated tablet 10 mg, Pioglitazone encapsulated tablet 30 mg, Linagliptin encapsulated tablet 5 mg in people with Impaired Glucose Tolerance and Insulin Sensitivity, run by Oslo University Hospital at 1 site in Norway.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 60 years, women only
- Conditions the study is for
- Impaired Glucose Tolerance, Insulin Sensitivity, Glucose Metabolism Disorders
- What is being tested?
- Metformin capsule 500 mg, Empagliflozin encapsulated tablet 10 mg, Pioglitazone encapsulated tablet 30 mg, Linagliptin encapsulated tablet 5 mg
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 64 participants
- Where
- 1 siteNorway
- Study dates
- 10 Feb 2021to Oct 2023
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 60 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- Able and willing to give informed consent
- Woman ≥ 18 years of age
- Of South Asian origin
- 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.
- 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
Who cannot join
- Known type 2 diabetes
- Known type 1 diabetes
- 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
- 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
Show all 24Show fewer
- 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.
- Active infectious disease at inclusion
- Use of systemic corticosteroids > 14 days within last 3 months before inclusion
- 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
- Previous or present acute metabolic acidosis.
- Known hypersensitivity to any of the active ingredients or additives in the study medication or placebo capsules.
- Macroscopic haematuria not previously examined
- History of major surgical procedures within 3 months prior to inclusion or planned during study period.
- 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.
Trial locations and contacts
1 site in 1 country.
Norway1 site, 1 recruiting
- Recruiting
Oslo University Hospital, Aker Hospital
Oslo, 0424, Nydalen
Åse Halsne, RN, +4722894745, asehal@ous-hf.no
About this study
Official title: Glucose Metabolism in South Asian Women With IGT or IFG. DIAbetes in South Asians - DIASA 3: A 12-week Intervention Trial With Oral Antidiabetic Medication to Improve Hepatic and Whole Body Insulin Sensitivity
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.
Read the detailed description
Background: South Asians (SA) have a high prevalence of type 2 diabetes (T2D). SA i Norway develop T2D approximately 10 years earlier than Nordic subjects (NO).T2D in SA is often poorly regulated with increased risk of complications.
Research hypothesis: South Asian subjects with Impaired glucose tolerance (IGT) or impaired fasting glucose (IFG) have a high degree of hepatic insulin resistance. Treatment with certain oral antidiabetic drugs will improve hepatic insulin sensitivity more than others.
Primary objective: To assess which of four oral antidiabetic medications is most effective in improving hepatic insulin sensitivity in women of South Asian origin with IFG/IGT.
Study design: Single-center, randomized, double-blind intervention trial with 4 parallel treatment arms: 1) Metformin 2) Pioglitazone 3) Empagliflozin 4) Linagliptin.
Endogenous glucose production (EGP) and hepatic and whole body insulin sensitivity will be assessed by a 2-step euglycemic, hyperinsulinemic clamp with deuterated glucose tracer. In addition, glucose and lipid metabolism will be assessed by indirect calorimetry (IC), insulin secretion by an oral glucose tolerance test (OGTT), and fatty infiltration in liver by computer tomography (CT).
Recruitment: From South Asian women with IFG/IGT who participated in DIASA 1.
Duration of study: 14 weeks, with a total of four study visits, every 4 weeks, plus two CT scans, at baseline and 12 weeks, and one end of study follow-up telephone visit at 14 weeks. The project is expected to last a maximum of 3 years.
Study population: Women ≥ 18 years of age of South Asian ethnicity with IGT/IFG.
Criteria for evaluation: Efficacy outcome will include evaluation of change in EGP from baseline to 12 weeks. Laboratory parameters of glucose and lipid metabolism. Questionnaires with physical activity and food frequency. Safety and tolerability will be assessed by clinical adverse events and laboratory measurements from randomization to 14 weeks.
Primary outcome: Difference between treatment arms in change in EGP from baseline to 12 weeks.
Explorative outcomes: Difference between treatment arms in change from randomisation to 12 weeks in:
- whole body insulin sensitivity
- HbA1c
- glucose and lipid metabolism measured by IC
- fatty infiltration in liver and visceral adipose tissue.
Statistical Methods: One-way ANOVA, Multiple regression analyses, Paired samples t-tests, longitudinal analyses.
- Being tested
- Metformin capsule 500 mg, Empagliflozin encapsulated tablet 10 mg, Pioglitazone encapsulated tablet 30 mg, Linagliptin encapsulated tablet 5 mg
- Medical subject headings
- Glucose Intolerance, Insulin Resistance, Glucose Metabolism Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Metformin capsule 500 mg, Empagliflozin encapsulated tablet 10 mg, Pioglitazone encapsulated tablet 30 mg, Linagliptin encapsulated tablet 5 mgDrug
Also called biguanide, glitazone, sodium glucose transport inhibitor, dipeptidyl peptidase inhibitor
Comparison of 4 different antihyperglycemic drugs
| Study group | Role | What they receive |
|---|---|---|
| Metformin | Active comparator | Metformin 500 mg x 1, morning, for 2 weeks, then Metformin 500 mg x 2, morning and evening for 10 weeks. Receives: 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. Receives: 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. Receives: 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. Receives: Drug: Metformin capsule 500 mg, Empagliflozin encapsulated tablet 10 mg, Pioglitazone encapsulated tablet 30 mg, Linagliptin encapsulated tablet 5 mg |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
Measured: After 12 weeks on respective drugs
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Dec 2020
- Study start10 Feb 2021
- Primary completionDec 2022 (estimated)
- Study completionOct 2023 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Impaired Glucose ToleranceStudies of the same condition, open and under way.
- More trials run by Oslo University HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Randomised controlled trial (RCT), 4 parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 64 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Oslo University Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- The Research Council of Norway, Norwegian Diabetes Association, South-Eastern Norway Regional Health Authority, University of Oslo, University Hospital, Akershus, Vestre Viken Hospital Trust, University of Glasgow
- Responsible party
- Principal investigator, Kåre Inge Birkeland, Oslo University Hospital
- Investigators
- Kåre I Birkeland, MD, PhD, Principal investigator, Professor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04662866
- Sponsor's protocol ID
- 24993
- Acronym
- DIASA3
- Status last verified
- Apr 2021
- First submitted
- 16 Nov 2020
- Last updated
- 8 Apr 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 Apr 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Glucose Metabolism in South Asian Women With IGT or IFG. DIAbetes in South Asians - DIASA 3: A 12-week Intervention Trial With Oral Antidiabetic Medication to Improve Hepatic and Whole Body Insulin Sensitivity
- ClinicalTrials.gov ID
- NCT04662866
- Acronym / sponsor ID
- DIASA3 / 24993
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 64 participants (estimated)
- Lead sponsor
- Oslo University HospitalUniversity, hospital or other
- Collaborators
- The Research Council of Norway, Norwegian Diabetes Association, South-Eastern Norway Regional Health Authority, University of Oslo, University Hospital, Akershus, Vestre Viken Hospital Trust, University of Glasgow
- Study start
- 10 Feb 2021 (actual)
- Primary completion
- Dec 2022 (estimated)
- Study completion
- Oct 2023 (estimated)
- First posted
- 10 Dec 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Background: South Asians (SA) have a high prevalence of type 2 diabetes (T2D). SA i Norway develop T2D approximately 10 years earlier than Nordic subjects (NO).T2D in SA is often poorly regulated with increased risk of complications.
Research hypothesis: South Asian subjects with Impaired glucose tolerance (IGT) or impaired fasting glucose (IFG) have a high degree of hepatic insulin resistance. Treatment with certain oral antidiabetic drugs will improve hepatic insulin sensitivity more than others.
Primary objective: To assess which of four oral antidiabetic medications is most effective in improving hepatic insulin sensitivity in women of South Asian origin with IFG/IGT.
Study design: Single-center, randomized, double-blind intervention trial with 4 parallel treatment arms: 1) Metformin 2) Pioglitazone 3) Empagliflozin 4) Linagliptin.
Endogenous glucose production (EGP) and hepatic and whole body insulin sensitivity will be assessed by a 2-step euglycemic, hyperinsulinemic clamp with deuterated glucose tracer. In addition, glucose and lipid metabolism will be assessed by indirect calorimetry (IC), insulin secretion by an oral glucose tolerance test (OGTT), and fatty infiltration in liver by computer tomography (CT).
Recruitment: From South Asian women with IFG/IGT who participated in DIASA 1.
Duration of study: 14 weeks, with a total of four study visits, every 4 weeks, plus two CT scans, at baseline and 12 weeks, and one end of study follow-up telephone visit at 14 weeks. The project is expected to last a maximum of 3 years.
Study population: Women ≥ 18 years of age of South Asian ethnicity with IGT/IFG.
Criteria for evaluation: Efficacy outcome will include evaluation of change in EGP from baseline to 12 weeks. Laboratory parameters of glucose and lipid metabolism. Questionnaires with physical activity and food frequency. Safety and tolerability will be assessed by clinical adverse events and laboratory measurements from randomization to 14 weeks.
Primary outcome: Difference between treatment arms in change in EGP from baseline to 12 weeks.
Explorative outcomes: Difference between treatment arms in change from randomisation to 12 weeks in:
- whole body insulin sensitivity
- HbA1c
- glucose and lipid metabolism measured by IC
- fatty infiltration in liver and visceral adipose tissue.
Statistical Methods: One-way ANOVA, Multiple regression analyses, Paired samples t-tests, longitudinal analyses.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
- Model description
- Randomised controlled trial (RCT), 4 parallel groups
| Arm | Type | Receives |
|---|---|---|
| Metformin | Active comparator | Drug: Metformin capsule 500 mg, Empagliflozin encapsulated tablet 10 mg, Pioglitazone encapsulated tablet 30 mg, Linagliptin encapsulated tablet 5 mgMetformin 500 mg x 1, morning, for 2 weeks, then Metformin 500 mg x 2, morning and evening for 10 weeks. |
| Empagliflozin | Active comparator | Drug: Metformin capsule 500 mg, Empagliflozin encapsulated tablet 10 mg, Pioglitazone encapsulated tablet 30 mg, Linagliptin encapsulated tablet 5 mgEmpagliflozin 10 mg x 1, morning, for 2 weeks, then Empagliflozin 10 mg morning + Placebo evening for 10 weeks. |
| Linagliptin | Active comparator | Drug: Metformin capsule 500 mg, Empagliflozin encapsulated tablet 10 mg, Pioglitazone encapsulated tablet 30 mg, Linagliptin encapsulated tablet 5 mgLinagliptin 5 mg x 1, morning, for 2 weeks, then Linagliptin 5 mg morning + Placebo evening for 10 weeks. |
| Pioglitazone | Active comparator | Drug: Metformin capsule 500 mg, Empagliflozin encapsulated tablet 10 mg, Pioglitazone encapsulated tablet 30 mg, Linagliptin encapsulated tablet 5 mgPioglitazone 30 mg x 1, morning, for 2 weeks, then Pioglitazone 30 mg morning + Placebo evening for 10 weeks. |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (5 listed)
- Able and willing to give informed consent
- Woman ≥ 18 years of age
- Of South Asian origin
- 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.
- 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
Key exclusion criteria (24 listed)
- Known type 2 diabetes
- Known type 1 diabetes
- 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
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Metformin capsule 500 mg, Empagliflozin encapsulated tablet 10 mg, Pioglitazone encapsulated tablet 30 mg, Linagliptin encapsulated tablet 5 mgAlso: biguanide, glitazone, sodium glucose transport inhibitor, dipeptidyl peptidase inhibitorComparison of 4 different antihyperglycemic drugs | Drug | Empagliflozin, Linagliptin, Metformin, Pioglitazone |
Primary outcome
Endogenous glucose production during fasting
Time frame: After 12 weeks on respective drugs
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)
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Apr 2021.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Kåre I Birkeland, MD, PhD principal investigator
Professor
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Metformin capsule 500 mg, Empagliflozin encapsulated tablet 10 mg, Pioglitazone encapsulated tablet 30 mg, Linagliptin encapsulated tablet 5 mg in people with Impaired Glucose Tolerance and Insulin Sensitivity, run by Oslo University Hospital at 1 site in Norway.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 24 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 8 Apr 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Norway. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Anita Suntharalingam, MD (+4722894745, ansunt@ous-hf.no), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Endogenous glucose production during fasting (time frame: After 12 weeks on respective drugs). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Apr 2021.