DiabetesPhase 2/3NCT00683735
Quantification of the Dipeptidyl Peptidase (DPP)-4 Inhibition-mediated Enhancement of the Activity of the Entero-insular Axis
A Phase 2/3 study testing Sitagliptin and Metformin in people with Diabetes, run by Michael A. Nauck at 1 site in Germany.
Trial summary
Objective: To assess the effect if co-administration of sitagliptin and metformin compared to placebo on the incretin effect (based on the comparison of the insulin secretory response to oral glucose load and an 'isoglycaemic' intravenous glucose load). Read more about this study
- Who is it for?
- Ages 30 to 75 years
- Conditions the study is for
- Diabetes
- What is being tested?
- Sitagliptin and Metformin
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 20 participants
- Where
- 1 siteGermany
- Study dates
- Feb 2009to Dec 2013
- Phase
- Phase 2/3
- 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 30 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Type 2-diabetes mellitus
- BMI 25-35 kg/m2
- HbA1c 6.5%-9% (without OHA medication)
- HbA1c 6%-8.5% (OHA monotherapy with metformin or sulfonylurea)
- Patient understands the study-procedures
Who cannot join
- Type 1-diabetes mellitus
- C-peptide < 0.7ng/mL (0.23 nmol/L)
- Patient has been taking oral anti-hyperglycemic agent (OHA) within the prior 12 weeks, except metformin or a sulfonylurea
- Patient has required insulin therapy within the past 12 weeks
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Quantification of the DPP-4 Inhibition-mediated Enhancement of the Activity of the Entero-insular Axis
Objective: To assess the effect if co-administration of sitagliptin and metformin compared to placebo on the incretin effect (based on the comparison of the insulin secretory response to oral glucose load and an 'isoglycaemic' intravenous glucose load). Hypothesis: Treatment with co-administration of sitagliptin and metformin provides a greater incretin effect compared to placebo.
Read the detailed description
A new class of antidiabetic agents, the DPP-4 inhibitors, are thought to protect endogenously secreted incretin hormones (e.g., GLP-1 and GIP) from proteolytic degradation and inactivation. Since GLP-1 has antidiabetogenic properties, an augmentation of meal-related responses of intact, biologically active GLP-1 can be expected to increase the impact of incretin stimulation to insulin secretory responses. The incretin effect in type 2 diabetic patients is reduced due to an impaired secretion of GLP-1 and a reduced insulinotropic effectiveness of GIP. Therefore, sitagliptin (DPP-4 inhibitor) will be studied in 20 type 2-diabetic patients, who will be treated sequentially (crossover design) with (a) placebo, (b) metformin alone, (c) Sitagliptin alone, and (d) a combination of metformin and Sitagliptin for periods of 6 days (with a washout period of 3 days between treatment. The insulin secretory response (insulin, C-peptide, insulin secretion rates determined by deconvolution analysis) will be compared between experiments with oral glucose (75 g) and "isoglycaemic" intravenous glucose infusions (20% glucose i.v.). The difference represents the "incretin effect". It is expected that the incretin effect in type 2-diabetic patients will be enhanced with sitagliptin treatment, especially combined with metformin.
A secondary objective is to relate the potential increase in the % incretin contribution to insulin secretory response after oral glucose (incretin effect) to changes in the oral glucose-induced response of intact GLP-1 and GIP (measured by specific RIAs). Thus, it will be established, to which degree sitagliptin acts as an "incretin enhancer" in type 2 diabetic patients.
This study will also determine how the combination of sitagliptin to metformin affects the incretin response and insulin secretory response. Metformin is a standard and widely used antihyperglycemic agent which lowers glycemic levels primarily through suppression of hepatic glucose output and improvement in peripheral insulin resistance, resulting in increased glucose transport and utilization by skeletal muscle. There are data to suggest that metformin increases endogenous GLP-1 levels in response to an oral glucose load in obese humans (1).
Therefore it is of relevance to confirm this novel activity of metformin in patients with type 2 diabetes, and to assess potential functional consequences regarding the incretin effect.
- Conditions
- Diabetes
- Being tested
- Sitagliptin, Metformin, Placebo
- Keywords
- Incretin, DPP-4, metformin, sitagliptin, insulin secretion
- Medical subject headings
- Diabetes Mellitus
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SitagliptinDrug
100 mg once daily in the morning
MetforminDrug
up to 2000 mg/day
PlaceboDrug
500mg 1-0-0-0
PlaceboDrug
100mg 1-0-0-0
| Study group | Role | What they receive |
|---|---|---|
| Treatment A | Active comparator | sitagliptin and placebo Receives: Drug: Sitagliptin; Drug: Placebo |
| Treatment B | Active comparator | placebo and metformin Receives: Drug: Metformin; Drug: Placebo |
| Treatment C | Active comparator | sitagliptin and metformin Receives: Drug: Sitagliptin; Drug: Metformin |
| Treatment D | Placebo comparator | placebo Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
To assess the effect of co-administration of sitagliptin and metformin compared to placebo on the incretin effect (based on the comparison of the insulin secretory response to oral glucose load and an 'isoglycaemic' intravenous glucose load)
Measured: 24 weeks
Secondary outcomes (1)
To assess the effect of sitagliptin compared with placebo on the incretin effect (based on the comparison of the insulin secretory response to oral glucose load and an 'isoglycaemic' intravenous glucose load)
Measured: 24 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 May 2008 (estimated)
- Study startFeb 2009
- Primary completionDec 2012
- Study completionDec 2013
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for DiabetesStudies 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 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
- Who is masked
- Participant, Care provider
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Michael A. Nauck
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Michael A. Nauck, Diabeteszentrum Bad Lauterberg im Harz
- Investigators
- Michael A. Nauck, Prof. Dr., Principal investigator, Diabeteszentrum Bad Lauterberg
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00683735
- Sponsor's protocol ID
- DZBL 2008-Nauck-01
- Other IDs
- EudraCT: 2008-001663-11
- Status last verified
- Dec 2015
- First submitted
- 21 May 2008
- Last updated
- 18 Dec 2015
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 18 Dec 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Quantification of the DPP-4 Inhibition-mediated Enhancement of the Activity of the Entero-insular Axis
- ClinicalTrials.gov ID
- NCT00683735
- Acronym / sponsor ID
- DZBL 2008-Nauck-01
- Conditions
- Diabetes
- Keywords
- Incretin, DPP-4, metformin, sitagliptin, insulin secretion
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Michael A. NauckUniversity, hospital or other
- Study start
- Feb 2009
- Primary completion
- Dec 2012 (actual)
- Study completion
- Dec 2013 (actual)
- First posted
- 23 May 2008 (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.
Objective: To assess the effect if co-administration of sitagliptin and metformin compared to placebo on the incretin effect (based on the comparison of the insulin secretory response to oral glucose load and an 'isoglycaemic' intravenous glucose load). Hypothesis: Treatment with co-administration of sitagliptin and metformin provides a greater incretin effect compared to placebo.
Detailed description
A new class of antidiabetic agents, the DPP-4 inhibitors, are thought to protect endogenously secreted incretin hormones (e.g., GLP-1 and GIP) from proteolytic degradation and inactivation. Since GLP-1 has antidiabetogenic properties, an augmentation of meal-related responses of intact, biologically active GLP-1 can be expected to increase the impact of incretin stimulation to insulin secretory responses. The incretin effect in type 2 diabetic patients is reduced due to an impaired secretion of GLP-1 and a reduced insulinotropic effectiveness of GIP. Therefore, sitagliptin (DPP-4 inhibitor) will be studied in 20 type 2-diabetic patients, who will be treated sequentially (crossover design) with (a) placebo, (b) metformin alone, (c) Sitagliptin alone, and (d) a combination of metformin and Sitagliptin for periods of 6 days (with a washout period of 3 days between treatment. The insulin secretory response (insulin, C-peptide, insulin secretion rates determined by deconvolution analysis) will be compared between experiments with oral glucose (75 g) and "isoglycaemic" intravenous glucose infusions (20% glucose i.v.). The difference represents the "incretin effect". It is expected that the incretin effect in type 2-diabetic patients will be enhanced with sitagliptin treatment, especially combined with metformin.
A secondary objective is to relate the potential increase in the % incretin contribution to insulin secretory response after oral glucose (incretin effect) to changes in the oral glucose-induced response of intact GLP-1 and GIP (measured by specific RIAs). Thus, it will be established, to which degree sitagliptin acts as an "incretin enhancer" in type 2 diabetic patients.
This study will also determine how the combination of sitagliptin to metformin affects the incretin response and insulin secretory response. Metformin is a standard and widely used antihyperglycemic agent which lowers glycemic levels primarily through suppression of hepatic glucose output and improvement in peripheral insulin resistance, resulting in increased glucose transport and utilization by skeletal muscle. There are data to suggest that metformin increases endogenous GLP-1 levels in response to an oral glucose load in obese humans (1).
Therefore it is of relevance to confirm this novel activity of metformin in patients with type 2 diabetes, and to assess potential functional consequences regarding the incretin effect.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, care provider)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Treatment A | Active comparator | Drug: Sitagliptin, Drug: Placebositagliptin and placebo |
| Treatment B | Active comparator | Drug: Metformin, Drug: Placeboplacebo and metformin |
| Treatment C | Active comparator | Drug: Sitagliptin, Drug: Metforminsitagliptin and metformin |
| Treatment D | Placebo comparator | Drug: Placeboplacebo |
Who may qualify
- Ages
- 30 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Type 2-diabetes mellitus
- BMI 25-35 kg/m2
- HbA1c 6.5%-9% (without OHA medication)
- HbA1c 6%-8.5% (OHA monotherapy with metformin or sulfonylurea)
- Patient understands the study-procedures
Key exclusion criteria (4 listed)
- Type 1-diabetes mellitus
- C-peptide < 0.7ng/mL (0.23 nmol/L)
- Patient has been taking oral anti-hyperglycemic agent (OHA) within the prior 12 weeks, except metformin or a sulfonylurea
- Patient has required insulin therapy within the past 12 weeks
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 |
|---|---|---|
| Sitagliptin100 mg once daily in the morning | Drug | Treatment A, Treatment C |
| Metforminup to 2000 mg/day | Drug | Treatment B, Treatment C |
| Placebo500mg 1-0-0-0 | Drug | Treatment A, Treatment D |
| Placebo100mg 1-0-0-0 | Drug | Treatment B, Treatment D |
Primary outcome
To assess the effect of co-administration of sitagliptin and metformin compared to placebo on the incretin effect (based on the comparison of the insulin secretory response to oral glucose load and an 'isoglycaemic' intravenous glucose load)
Time frame: 24 weeks
1 secondary outcome
To assess the effect of sitagliptin compared with placebo on the incretin effect (based on the comparison of the insulin secretory response to oral glucose load and an 'isoglycaemic' intravenous glucose load)
Time frame: 24 weeks
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 Dec 2015.
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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.
Michael A. Nauck, Prof. Dr. principal investigator
Diabeteszentrum Bad Lauterberg
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Sitagliptin and Metformin in people with Diabetes, run by Michael A. Nauck at 1 site in Germany.
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 4 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 Dec 2015. 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 Germany. 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined 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.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
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?
To assess the effect of co-administration of sitagliptin and metformin compared to placebo on the incretin effect (based on the comparison of the insulin secretory response to oral glucose load and an 'isoglycaemic' intravenous glucose load) (time frame: 24 weeks). 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 Dec 2015.