Diabetes Mellitus, Type 2Phase 4NCT00118963
Effect of Repaglinide Versus Metformin Treatment in Non-Obese Patients With Type-2-Diabetes
A Phase 4 study testing Metformin, Insulin BIAsp30 (Novolog 70/30) and Repaglinide in people with Diabetes Mellitus, Type 2, run by Steno Diabetes Center Copenhagen at 1 site in Denmark.
Trial summary
Aim: The United Kingdom Prospective Diabetes Study (UKPDS) showed a reduction in cardiovascular events in obese patients with type-2-diabetes treated with metformin compared with other hypoglycaemic treatments with no difference in glycemic control between treatments. Read more about this study
- Who is it for?
- Ages 40 years and older
- Conditions the study is for
- Diabetes Mellitus, Type 2
- What is being tested?
- Metformin, Insulin BIAsp30 (Novolog 70/30) and Repaglinide
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 102 participants
- Where
- 1 siteDenmark
- Study dates
- Jan 2003to Feb 2006
- Phase
- Phase 4
- 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 40 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Non-obese patients (BMI < 27 kg/m2)
- Type 2 diabetes
- Age 40 years or older
- HbA1c = 6.5% or higher at baseline.
Who cannot join
- No known contraindications for either of the study-drugs (known allergy to the study-drugs; heart-, liver- or kidney-failure)
- Pregnancy
- Other serious physical or mental illnesses with a life-shortening prognosis.
- Drug or alcohol abuse.
- Weight-loss of more than 5 kg during the last 6 month prior to enrollment.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Effect of Repaglinide Versus Metformin Treatment in Combination With Insulin Biasp30 (Novologmix 70/30) Predinner on Glycemic and Non-Glycemic Cardiovascular Risk-Factors in Non-Obese Patients With Type-2-Diabetes With Unsatisfactory Glycaemic Control With Oral Hypoglycaemic Agents
Aim:
The United Kingdom Prospective Diabetes Study (UKPDS) showed a reduction in cardiovascular events in obese patients with type-2-diabetes treated with metformin compared with other hypoglycaemic treatments with no difference in glycemic control between treatments. Non-obese patients with type-2-diabetes are usually treated with insulin-secretagogues or insulin when diet fails. Since non-obese patients with type-2-diabetes also carry a high risk of cardiovascular events, the use of metformin for this sub-group of patients might be more beneficial. Moreover, when insulin-treatment is initiated ongoing oral hypoglycaemic agents (OHA) are often continued, but in non-obese patients with type-2 diabetes little evidence exist for choosing the optimal class of OHA to be combined with insulin. The aim of the project is therefore to investigate the effect of metformin vs. an insulin-secretagogue (repaglinide) in combination with insulin on glycemic control and non-glycemic cardiovascular risk-factors in non-obese patients with type-2-diabetes, uncontrolled on diet alone.
Read more
Methodology:
Single-center, double-blind, double-dummy, randomized, parallel study involving 100 non-obese (BMI 27 kg/m2 or lower) patients with type-2-diabetes investigating the effect of treatment with metformin vs. repaglinide each in combination with biphasic insulin (Insulin-aspart 30/70, BIAsp30) for a period of 12 months.
Read the detailed description
After four months run-in with repaglinide plus metformin combination-therapy, patients with HemoglobinA1c ≥6.5% will be randomized (baseline=0 month) to repaglinide 2 mg thrice-daily or metformin 1g twice-daily, both in combination with BIAsp30 (30% insulin-aspart; 70% protaminated insulin-aspart) (6U once-daily, pre-dinner) for 12 months.
- Conditions
- Diabetes Mellitus, Type 2
- Being tested
- Metformin, Insulin BIAsp30 (Novolog 70/30), Repaglinide, Placebo-Metformin, Placebo-Repaglinide
- Medical subject headings
- Diabetes Mellitus, Type 2
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MetforminDrug
Tablets of 500 mg; 1000 mg two times daily.
Insulin BIAsp30 (Novolog 70/30)Drug
Subcutaneous injection. Starting dose 6 units. Titration according to glycaemic targets during the entire intervention period.
RepaglinideDrug
Tablets of 1 mg; Dosage: 2 mg three times daily.
Placebo-MetforminDrug
Tablets corresponding to 500 mg; two tablets two times daily.
Placebo-RepaglinideDrug
Tablet corresponding to 1 mg; two tablets three times daily.
| Study group | Role | What they receive |
|---|---|---|
| 3 | Active comparator | BIAsp30 plus Metformin plus Placebo-Repaglinide. Double-Masked and randomized. Duration: 12 months. Receives: Drug: Metformin; Drug: Insulin BIAsp30 (Novolog 70/30); Drug: Placebo-Repaglinide |
| 2 | Active comparator | BIAsp30 plus Repaglinide plus Placebo-Metformin. Double-masked and randomized. Duration: 12 months. Receives: Drug: Insulin BIAsp30 (Novolog 70/30); Drug: Repaglinide; Drug: Placebo-Metformin |
| 1 | Other | Run-in period of four months duration with Repaglinide 6 mg daily plus Metformin 2000 mg daily. No masking of interventions. Receives: Drug: Metformin; Drug: Repaglinide |
What is being measured
The primary outcome is the main question the study is designed to answer.
Glycemic control (HbA1c).
Secondary outcomes (7)
Hypoglycaemic events
Home monitored plasma-glucose profiles
Insulin-dose
Non-glycemic cardiovascular risk factors: 24h blood-pressure measurement
24h urinary albumin excretion-rate.
Fasting and postprandial 5-point-profiles of total-cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides, free fatty acids, p-glucose, c-peptide and insulin after a standard test-meal
Markers of endothelial dysfunction, inflammation and fibrinolysis including Small-dense-LDL, Lp(a) and Apo B100, von Willebrand-factor, ICAM, VCAM, selectin, endothelin, Amadori-protein, CRP, fibrinogen, IL-6, TNF-alfa, ADMA, PAI- and t-PA-activity
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Jul 2005 (estimated)
- Study startJan 2003
- Primary completionFeb 2006
- Study completionFeb 2006
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Diabetes Mellitus, Type 2Studies of the same condition, open and under way.
- 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 102 participants (actual)
Sponsor and investigators
- Lead sponsor
- Steno Diabetes Center Copenhagen
- Sponsor type
- University, hospital or other
- Investigators
- Allan A Vaag, M.D. Chief Physician, Study chair, Steno Diabetes Center Copenhagen
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00118963
- Sponsor's protocol ID
- Reform
- Status last verified
- Dec 2008
- First submitted
- 1 Jul 2005
- Last updated
- 8 Dec 2008
- Results posted
- No
Publications
Lund SS, Tarnow L, Frandsen M, Nielsen BB, Hansen BV, Pedersen O, Parving HH, Vaag AA. Combining insulin with metformin or an insulin secretagogue in non-obese patients with type 2 diabetes: 12 month, randomised, double blind trial. BMJ. 2009 Nov 9;339:b4324. doi: 10.1136/bmj.b4324.
PubMed 19900993
Study at a glance
From the registry record, last updated by the sponsor on 8 Dec 2008. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of Repaglinide Versus Metformin Treatment in Combination With Insulin Biasp30 (Novologmix 70/30) Predinner on Glycemic and Non-Glycemic Cardiovascular Risk-Factors in Non-Obese Patients With Type-2-Diabetes With Unsatisfactory Glycaemic Control With Oral Hypoglycaemic Agents
- ClinicalTrials.gov ID
- NCT00118963
- Acronym / sponsor ID
- Reform
- Conditions
- Diabetes Mellitus, Type 2
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 102 participants (actual)
- Lead sponsor
- Steno Diabetes Center CopenhagenUniversity, hospital or other
- Study start
- Jan 2003
- Primary completion
- Feb 2006 (actual)
- Study completion
- Feb 2006 (actual)
- First posted
- 12 Jul 2005 (estimated)
- 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.
Aim:
The United Kingdom Prospective Diabetes Study (UKPDS) showed a reduction in cardiovascular events in obese patients with type-2-diabetes treated with metformin compared with other hypoglycaemic treatments with no difference in glycemic control between treatments. Non-obese patients with type-2-diabetes are usually treated with insulin-secretagogues or insulin when diet fails. Since non-obese patients with type-2-diabetes also carry a high risk of cardiovascular events, the use of metformin for this sub-group of patients might be more beneficial. Moreover, when insulin-treatment is initiated ongoing oral hypoglycaemic agents (OHA) are often continued, but in non-obese patients with type-2 diabetes little evidence exist for choosing the optimal class of OHA to be combined with insulin. The aim of the project is therefore to investigate the effect of metformin vs. an insulin-secretagogue (repaglinide) in combination with insulin on glycemic control and non-glycemic cardiovascular risk-factors in non-obese patients with type-2-diabetes, uncontrolled on diet alone.
Methodology:
Single-center, double-blind, double-dummy, randomized, parallel study involving 100 non-obese (BMI 27 kg/m2 or lower) patients with type-2-diabetes investigating the effect of treatment with metformin vs. repaglinide each in combination with biphasic insulin (Insulin-aspart 30/70, BIAsp30) for a period of 12 months.
Detailed description
After four months run-in with repaglinide plus metformin combination-therapy, patients with HemoglobinA1c ≥6.5% will be randomized (baseline=0 month) to repaglinide 2 mg thrice-daily or metformin 1g twice-daily, both in combination with BIAsp30 (30% insulin-aspart; 70% protaminated insulin-aspart) (6U once-daily, pre-dinner) for 12 months.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| 3 | Active comparator | Drug: Metformin, Drug: Insulin BIAsp30 (Novolog 70/30), Drug: Placebo-RepaglinideBIAsp30 plus Metformin plus Placebo-Repaglinide. Double-Masked and randomized. Duration: 12 months. |
| 2 | Active comparator | Drug: Insulin BIAsp30 (Novolog 70/30), Drug: Repaglinide, Drug: Placebo-MetforminBIAsp30 plus Repaglinide plus Placebo-Metformin. Double-masked and randomized. Duration: 12 months. |
| 1 | Other | Drug: Metformin, Drug: RepaglinideRun-in period of four months duration with Repaglinide 6 mg daily plus Metformin 2000 mg daily. No masking of interventions. |
Who may qualify
- Ages
- 40 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- Non-obese patients (BMI < 27 kg/m2)
- Type 2 diabetes
- Age 40 years or older
- HbA1c = 6.5% or higher at baseline.
Key exclusion criteria (5 listed)
- No known contraindications for either of the study-drugs (known allergy to the study-drugs; heart-, liver- or kidney-failure)
- Pregnancy
- Other serious physical or mental illnesses with a life-shortening prognosis.
- Drug or alcohol abuse.
- Weight-loss of more than 5 kg during the last 6 month prior to enrollment.
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 |
|---|---|---|
| MetforminTablets of 500 mg; 1000 mg two times daily. | Drug | 1, 3 |
| Insulin BIAsp30 (Novolog 70/30)Subcutaneous injection. Starting dose 6 units. Titration according to glycaemic targets during the entire intervention period. | Drug | 2, 3 |
| RepaglinideTablets of 1 mg; Dosage: 2 mg three times daily. | Drug | 1, 2 |
| Placebo-MetforminTablets corresponding to 500 mg; two tablets two times daily. | Drug | 2 |
| Placebo-RepaglinideTablet corresponding to 1 mg; two tablets three times daily. | Drug | 3 |
Primary outcome
Glycemic control (HbA1c).
7 secondary outcomes
Hypoglycaemic events
Home monitored plasma-glucose profiles
Insulin-dose
Non-glycemic cardiovascular risk factors: 24h blood-pressure measurement
24h urinary albumin excretion-rate.
Fasting and postprandial 5-point-profiles of total-cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides, free fatty acids, p-glucose, c-peptide and insulin after a standard test-meal
Markers of endothelial dysfunction, inflammation and fibrinolysis including Small-dense-LDL, Lp(a) and Apo B100, von Willebrand-factor, ICAM, VCAM, selectin, endothelin, Amadori-protein, CRP, fibrinogen, IL-6, TNF-alfa, ADMA, PAI- and t-PA-activity
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Dec 2008.
- Derived from this study: PubMed 19900993Lund SS, Tarnow L, Frandsen M, Nielsen BB, Hansen BV, Pedersen O, Parving HH, Vaag AA. Combining insulin with metformin or an insulin secretagogue in non-obese patients with type 2 diabetes: 12 month, randomised, double blind trial. BMJ. 2009 Nov 9;339:b4324. doi: 10.1136/bmj.b4324.
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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.
Allan A Vaag, M.D. Chief Physician study chair
Steno Diabetes Center Copenhagen
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Metformin, Insulin BIAsp30 (Novolog 70/30) and Repaglinide in people with Diabetes Mellitus, Type 2, run by Steno Diabetes Center Copenhagen at 1 site in Denmark.
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 4 inclusion and 5 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: finished, as of the sponsor's last update on 8 Dec 2008. 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 Denmark. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Glycemic control (HbA1c).. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00118963, which also lists 1 linked publication.
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 Dec 2008.