Type 2 DiabetesPhase 4NCT02188186
Therapeutic Efficacy of Triple Combination in Drug-naïve Korean Type 2 Diabetic Patients
A Phase 4 study testing Initial triple combination and Conventional treatment in people with Type 2 Diabetes, run by Seoul National University Bundang Hospital at 1 site in South Korea.
Trial summary
Triple combination of metformin, DPP4 inhibitor and Thiazolidinedione would be a good option in the treatment of drug-naïve Korean type 2 diabetic patients. Read more about this study
- Who is it for?
- Ages 20 to 80 years
- Conditions the study is for
- Type 2 Diabetes
- What is being tested?
- Initial triple combination and Conventional treatment
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 200 participants
- Where
- 1 siteSouth Korea
- Study dates
- Jul 2014to Sep 2018
- 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 20 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- HbA1c 9-12%
- No treatment with insulin or oral agents for recent 6 months
- 20 ≤ Age < 80 years
Who cannot join
- Contraindication to sitagliptin or metformin or thiazolidinedione
- Pregnant or breast feeding women
- Type 1 diabetes, gestational diabetes, or secondary forms of diabetes
- Not appropriate for oral antidiabetic agent
- Medication which affect glycemic control
- Disease which affect efficacy and safety of drugs
- Any major illness (Liver disease, Renal failure, Heart disease, Cancer, etc)
Trial locations and contacts
1 site in 1 country.
South Korea1 site
Seoul National University Bundang Hospital
Seongnam-si, Gyeonggi-do, 463-707
About this study
Official title: Therapeutic Efficacy of Triple Combination of Metformin, DPP4 Inhibitor and Thiazolidinedione in Drug-naïve Korean Type 2 Diabetic Patients
Triple combination of metformin, DPP4 inhibitor and Thiazolidinedione would be a good option in the treatment of drug-naïve Korean type 2 diabetic patients.
Read the detailed description
Thiazolidionedione, a PPARgamman agonist, is an strong insulin sensitizer. It has shown that durable glucose lowering effect and beta cell preservation. It is an important treatment option in patients with type 2 diabetes.
It has been well established that inhibition of dipeptidyl peptidase-4 (DPP-4) reduces blood glucose levels in both fasting and postprandial states, and preserves pancreatic β-cell function in patients with type 2 diabetes. The mechanism of action of DPP-4 inhibitors is to increase levels of active incretin, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), which stimulate insulin secretion as well as insulin biosynthesis while inhibiting glucagon release from pancreatic islets.
DPP4 inhibitors also have better safety and tolerability profiles (e.g., weight neutrality and less hypoglycemia) compared to other hypoglycemic agents. When considering combination therapy with DPP-4 inhibitors, metformin is the most commonly used agent which has been shown to be effective and well tolerated from previous studies. Besides the glucose lowering effect by reducing hepatic glucose output and improving insulin resistance, metformin without inhibiting DPP-4 activity,also increases active GLP-1 concentrations by 1.5- to 2-fold following an oral glucose load in obese, nondiabetic subjects. Accordingly, this effect of metformin may provide a unique benefit when combined with DPP-4 inhibitors through a substantial enhancement of the incretin axis, which provides effective and potentially additive glycemic improvement.
Because of its favorable pharmacological properties, combination of a DPP-4 inhibitor, metformin, and thiazolidinedione has been increasingly used to achieve rapid glycemic goal with low risk of hypoglycemia and no weight gain, and to delay the need for subsequent regimen changes. DPP-4 inhibitors block DPP-4 enzyme and preserve endogenous incretins whereas metformin increases the active form of GLP-1, both of which may enhance the secretory function of pancreas. However, the response to DPP-4 inhibitors and metformin combination therapy may be different in individuals according to their pancreatic function and insulin resistance status. In fact, previous studies with DPP-4 inhibitors showed different potency in glycemic controls depending on various patient characteristics including severity of diabetes and the use of other antidiabetic drug.Consequently, it would be clinically important to investigate effect of this triple combination therapy.
- Conditions
- Type 2 Diabetes
- Being tested
- Initial triple combination, Conventional treatment
- Keywords
- triple combination, metformin, sitagliptin, thiazolidinedione
- 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.
Initial triple combinationDrug
Also called metformin+sitagliptin (Januvia)+lobeglitazone (Duvie)
Initial triple combination arm
Conventional treatmentDrug
Also called metformin+sulfonylurea with dose escalation
Conventioanl treament with dose escalation
| Study group | Role | What they receive |
|---|---|---|
| Conventional treatment | Active comparator | Initial dual combination therapy with sulfonylurea and metfomin. Dose of sulfonylurea (glimepride 2-8 mg) and metfomin (500-2550 mg) can be ecalated at investigator's discreition at every visit.
Insulin therpy can be added as a rescue therapy at investigator's discreition. Receives: Drug: Conventional treatment |
| Initial triple combination treatment | Experimental | Initial dual combination therapy with metformin, sitagliptin (Januvia 100 mg), and lobeglitazone (Duvie 0.5 mg).
Insulin therpy can be added as a rescue therapy at investigator's discreition. Receives: Drug: Initial triple combination |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change of HbA1c
Therapeutic efficacy of triple combination of metform, sitagliptin, and lobeglitazone compared with sulfonylurea and metformin in drug-naïve Korean type 2 diabetic patients
Measured: 12 months
Secondary outcomes (7)
beta-cell function
Changes of beta-cell function after one year treatment
Measured: 12 months
Insulin resistance
Changes of Insulin resistance after one year treatment
Measured: 12 months
Glucose homeostasis
Changes in fasting glucose concentration
Measured: 12 months
Glucose metabolism
Area under the curve of glucose during OGTT
Measured: 12 months
Glucose metabolism
Area under the curve of insulin during OGTT
Measured: 12 months
Microalbuminuria
urine microalbumin to creatinine ratio
Measured: 12 months
Lipid profile
Changes in TG/HDL/LDL-concentrations
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jul 2014 (estimated)
- Study startJul 2014
- Primary completionSep 2018
- Study completionSep 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Type 2 DiabetesStudies of the same condition, open and under way.
- More trials run by Seoul National University Bundang 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Outcomes assessor
- Enrolment
- 200 participants (actual)
Sponsor and investigators
- Lead sponsor
- Seoul National University Bundang Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Soo Lim, Seoul National University Bundang Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02188186
- Sponsor's protocol ID
- Triple
- Status last verified
- Mar 2019
- First submitted
- 7 Jul 2014
- Last updated
- 18 Mar 2019
- 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 18 Mar 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Therapeutic Efficacy of Triple Combination of Metformin, DPP4 Inhibitor and Thiazolidinedione in Drug-naïve Korean Type 2 Diabetic Patients
- ClinicalTrials.gov ID
- NCT02188186
- Acronym / sponsor ID
- Triple
- Conditions
- Type 2 Diabetes
- Keywords
- triple combination, metformin, sitagliptin, thiazolidinedione
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 200 participants (actual)
- Lead sponsor
- Seoul National University Bundang HospitalUniversity, hospital or other
- Study start
- Jul 2014 (actual)
- Primary completion
- Sep 2018 (actual)
- Study completion
- Sep 2018 (actual)
- First posted
- 11 Jul 2014 (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.
Triple combination of metformin, DPP4 inhibitor and Thiazolidinedione would be a good option in the treatment of drug-naïve Korean type 2 diabetic patients.
Detailed description
Thiazolidionedione, a PPARgamman agonist, is an strong insulin sensitizer. It has shown that durable glucose lowering effect and beta cell preservation. It is an important treatment option in patients with type 2 diabetes.
It has been well established that inhibition of dipeptidyl peptidase-4 (DPP-4) reduces blood glucose levels in both fasting and postprandial states, and preserves pancreatic β-cell function in patients with type 2 diabetes. The mechanism of action of DPP-4 inhibitors is to increase levels of active incretin, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), which stimulate insulin secretion as well as insulin biosynthesis while inhibiting glucagon release from pancreatic islets.
DPP4 inhibitors also have better safety and tolerability profiles (e.g., weight neutrality and less hypoglycemia) compared to other hypoglycemic agents. When considering combination therapy with DPP-4 inhibitors, metformin is the most commonly used agent which has been shown to be effective and well tolerated from previous studies. Besides the glucose lowering effect by reducing hepatic glucose output and improving insulin resistance, metformin without inhibiting DPP-4 activity,also increases active GLP-1 concentrations by 1.5- to 2-fold following an oral glucose load in obese, nondiabetic subjects. Accordingly, this effect of metformin may provide a unique benefit when combined with DPP-4 inhibitors through a substantial enhancement of the incretin axis, which provides effective and potentially additive glycemic improvement.
Because of its favorable pharmacological properties, combination of a DPP-4 inhibitor, metformin, and thiazolidinedione has been increasingly used to achieve rapid glycemic goal with low risk of hypoglycemia and no weight gain, and to delay the need for subsequent regimen changes. DPP-4 inhibitors block DPP-4 enzyme and preserve endogenous incretins whereas metformin increases the active form of GLP-1, both of which may enhance the secretory function of pancreas. However, the response to DPP-4 inhibitors and metformin combination therapy may be different in individuals according to their pancreatic function and insulin resistance status. In fact, previous studies with DPP-4 inhibitors showed different potency in glycemic controls depending on various patient characteristics including severity of diabetes and the use of other antidiabetic drug.Consequently, it would be clinically important to investigate effect of this triple combination therapy.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Conventional treatment | Active comparator | Drug: Conventional treatmentInitial dual combination therapy with sulfonylurea and metfomin. Dose of sulfonylurea (glimepride 2-8 mg) and metfomin (500-2550 mg) can be ecalated at investigator's discreition at every visit. Insulin therpy can be added as a rescue therapy at investigator's discreition. |
| Initial triple combination treatment | Experimental | Drug: Initial triple combinationInitial dual combination therapy with metformin, sitagliptin (Januvia 100 mg), and lobeglitazone (Duvie 0.5 mg). Insulin therpy can be added as a rescue therapy at investigator's discreition. |
Who may qualify
- Ages
- 20 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- HbA1c 9-12%
- No treatment with insulin or oral agents for recent 6 months
- 20 ≤ Age < 80 years
Key exclusion criteria (7 listed)
- Contraindication to sitagliptin or metformin or thiazolidinedione
- Pregnant or breast feeding women
- Type 1 diabetes, gestational diabetes, or secondary forms of diabetes
- Not appropriate for oral antidiabetic agent
- Medication which affect glycemic control
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 |
|---|---|---|
| Initial triple combinationAlso: metformin+sitagliptin (Januvia)+lobeglitazone (Duvie)Initial triple combination arm | Drug | Initial triple combination treatment |
| Conventional treatmentAlso: metformin+sulfonylurea with dose escalationConventioanl treament with dose escalation | Drug | Conventional treatment |
Primary outcome
Change of HbA1c
Time frame: 12 months
Therapeutic efficacy of triple combination of metform, sitagliptin, and lobeglitazone compared with sulfonylurea and metformin in drug-naïve Korean type 2 diabetic patients
7 secondary outcomes
beta-cell function
Time frame: 12 months
Insulin resistance
Time frame: 12 months
Glucose homeostasis
Time frame: 12 months
Glucose metabolism
Time frame: 12 months
Glucose metabolism
Time frame: 12 months
Microalbuminuria
Time frame: 12 months
Lipid profile
Time frame: 12 months
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 18 Mar 2019.
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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.
The record lists no contact. Use the official record to reach the sponsor.
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 Initial triple combination and Conventional treatment in people with Type 2 Diabetes, run by Seoul National University Bundang Hospital at 1 site in South Korea.
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 3 inclusion and 7 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 18 Mar 2019. 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 South Korea. 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?
Change of HbA1c (time frame: 12 months). 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 18 Mar 2019.