DiabetesPhase 4NCT00820573
Mechanisms of Glucose Lowering Effects of Sitagliptin and Metformin Alone and in Combination in Patients With T2DM
A Phase 4 study testing Sitagliptin, Metformin and Sitagliptin + Metformin in people with Diabetes, run by The University of Texas Health Science Center at San Antonio at 1 site in United States.
Trial summary
In patients with type 2 diabetes with inadequate glycemic control on diet and exercise after 6 weeks of treatment: Objective: To assess the effects of co-administration of sitagliptin and metformin compared to placebo on hepatic glucose production (HGP). Read more about this study
- Who is it for?
- Ages 18 to 70 yearsHealthy volunteers can take part
- Conditions the study is for
- Diabetes
- What is being tested?
- Sitagliptin, Metformin and Sitagliptin + Metformin
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 16 participants
- Where
- 1 siteUnited States
- Study dates
- Oct 2009to Oct 2012
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 70 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Patients must meet all of the following inclusion criteria to participate in the study.
- Patients with screening values/findings outside ranges described in the protocol may have one repeat determination performed and if the repeat value satisfies the criterion, they may continue in the screening process.
- If the repeat value does not satisfy the criterion, the principal investigator will review the abnormal laboratory value and decide whether the subject may continue in the screening process.
- All screening laboratory measurements are to be performed after an overnight fast ≥10 hours in duration.
- Patients must be able to communicate meaningfully with the investigator and must be legally competent to provide written informed consent.
- Patients can be either male or female.
Show all 21Show fewer
- Patients are ≥18 and ≤70 years of age on the day of signing informed consent.
- Patients must meet the current American Diabetes Association criteria for the diagnosis of type 2 diabetes mellitus
- Patients must be on diet or diet plus exercise therapy.
- Patients must have a HbA1c ≥ 7.5% and ≤ 9.5%
- Patients must have a BMI of 23-40 kg/m2
- Patients must have the following laboratory values:
- Hematocrit Males ≥ 34 vol%
- Females ≥ 33vol%
- Serum creatinine ≤ 1.5 mg/dL in males and ≤ 1.4 mg/dL in females
- AST (SGOT): ≤ 2.5 times upper limit of normal
- ALT (SGPT): ≤ 2.5 times upper limit of normal
- Alkaline phosphatase ≤ 2.5 times upper limit of normal
- If serum creatinine is > 1.5 mg/dl in males and > 1.4 mg/dl in females, the Principal Investigator can include the patient if the measured GFR is >70 ml/min (24 hour creatinine clearance)
- Patients must have been on a stable dose of allowed chronic medications for ≥30 days prior to entering the study.
- Only patients whose body weight has been stable (±4 pounds) over the three months prior to the study will be included.
Who cannot join
- Patients are excluded from participation in the study if they meet any of the following criteria:
- Patient has type 1 diabetes.
- Patient has received insulin for more than one week within the previous year prior to entry.
- Patient has been treated with exenatide or a non-TZD, oral antihyperglycemic agent within the last 2 months or with a TZD (pioglitazone or rosiglitazone) within the last 4 months.
- Patient is receiving any medications with known adverse effects on glucose tolerance (e.g., systemic glucocorticoids, psychotropic drugs like clozapine, olanzapine, haloperidol, risperidone). Note: Patients may be taking stable doses of estrogens, other hormonal replacement therapy, or lipid and blood pressure lowering agents if the patient has been on these agents for the prior three months.
- Patient has evidence of a significant cardiovascular disorder within 6 months of signing informed consent (e.g. acute coronary syndrome, coronary artery intervention, stroke or transient ischemic neurological disorder) or has New York Heart Association Classification greater than Class 2; or has significant findings on ECG (other than non-specific ST-T wave changes); or peripheral vascular disease (history of claudication); or has dyspnea on exertion of one flight or less, or abnormal breath sounds on auscultation.
- Patient has a history of intolerance or hypersensitivity to a DPP-4 inhibitor or to metformin.
- Patient is pregnant or plans to become pregnant within the projected duration of the study.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Mechanisms of Glucose Lowering Effects of Sitagliptin and Metformin Alone and in Combination in Patients With Type 2 Diabetes Mellitus
In patients with type 2 diabetes with inadequate glycemic control on diet and exercise after 6 weeks of treatment:
Objective: To assess the effects of co-administration of sitagliptin and metformin compared to placebo on hepatic glucose production (HGP).
Hypothesis: After 6 weeks of treatment, the co-administration of sitagliptin and metformin provides greater reduction in hepatic glucose production (HGP) compared to placebo.
Read the detailed description
PRIMARY:
In patients with type 2 diabetes with inadequate glycemic control on diet and exercise after 6 weeks of treatment:
Objective: To assess the effects of co-administration of sitagliptin and metformin compared to placebo on hepatic glucose production (HGP).
Hypothesis: After 6 weeks of treatment, the co-administration of sitagliptin and metformin provides greater reduction in hepatic glucose production (HGP) compared to placebo.
SECONDARY:
In patients with type 2 diabetes with inadequate glycemic control on diet and exercise after 6 weeks of treatment:
- Objective: To assess the effects of co-administration of sitagliptin and metformin compared to placebo on post-meal glucose during meal tolerance test (MTT). Hypothesis: After 6 weeks of treatment the co-administration of sitagliptin and metformin provides greater reduction in the total glucose AUC (0-6 hr) during MTT compared to placebo.
- Objective: To assess the effects of co-administration of sitagliptin and metformin compared to placebo on fasting plasma glucose (FPG). Hypothesis: After 6 weeks of treatment the co-administration of sitagliptin and metformin provides greater reduction in FPG compared to placebo.
- Objective: To assess the effects sitagliptin alone compared to placebo on HGP. Hypothesis: After 6 weeks of treatment, sitagliptin alone provides greater reduction in HGP compared to placebo
EXPLORATORY OBJECTIVES:
(i) Objective: after 6 weeks of treatment, to assess the effects co-administration of sitagliptin and metformin compared to placebo on:
- active and inactive incretin concentrations (fasting and post-meal GLP-1 and fasting and post-meal GIP).
- glucagon concentration (fasting and post-meal).
- parameters of insulin secretion and insulin sensitivity.
- splanchnic glucose uptake. (ii) Objective: after 6 weeks of treatment, to assess the effects co-administration of sitagliptin and metformin compared to treatment with sitagliptin alone and metformin alone on:
- glucose concentration (fasting and total glucose AUC [0-6 hr]).
- active and inactive incretin concentrations (fasting and post-meal GLP-1 and fasting and post-meal GIP).
- glucagon concentration (fasting and post-meal).
- parameters of insulin secretion and insulin sensitivity.
- HGP.
- splanchnic glucose uptake. (iii) Objective: after 6 weeks of treatment, to assess the effects of sitagliptin alone and metformin alone compared to placebo on:
- glucose concentration (fasting and total glucose AUC [0-6 hr]).
- active and inactive incretin concentrations (fasting and post-meal GLP-1 and fasting and post-meal GIP).
- glucagon concentration (fasting and post-meal).
- parameters of insulin secretion and insulin sensitivity.
- HGP.
- splanchnic glucose uptake.
- Conditions
- Diabetes
- Being tested
- Sitagliptin, Metformin, Sitagliptin + Metformin, Placebo
- Keywords
- Diabetes
- 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
Also called Januvia
tablet, 100 mg/day, 6 weeks
MetforminDrug
Also called Glucophage
tablet, 1000 mg/ bid, 6 weeks
Sitagliptin + MetforminDrug
Also called Januvia and glucophage
tablet, Sitagliptin (100mg/day) + tablet, Metformin (1000 mg/bid), 6 weeks
PlaceboDrug
Also called Placebo tablet
Placebo 6 weeks
| Study group | Role | What they receive |
|---|---|---|
| Placebo | Placebo comparator | Placebo to be provided for 6 weeks Receives: Drug: Placebo |
| Sitagliptin | Experimental | Sitagliptin to be provided for 6 weeks Receives: Drug: Sitagliptin |
| Metformin | Experimental | Metformin to be provided for 6 weeks Receives: Drug: Metformin |
| Sitagliptin+Metfromin | Experimental | Sitagliptin + Metformin combined will be provided for 6 weeks Receives: Drug: Sitagliptin + Metformin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Objective: Comparisons of the Effects of Co-administration of Sitagliptin and Metformin Alone or in Combination Versus Placebo on Baseline Endogenous Glucose Production (EGP).
Baseline endogenous glucose production prior to a mixed meal tolerance test (placebo) and following 6 weeks of either sitagliptin, metformin or sitagliptin plus metformin combination therapy in all 16 participants
Measured: 6 weeks
Average of Plasma Glucose During Mixed Meal Tolerance Test (MTT) Compared to Baseline Plasma Glucose to Post Therapy (6-weeks).
The degree of suppression of baseline endogenous glucose production was measured in absolute values and as a percent of basal values at the end of each 6-week therapeutic period. The absolute values obtained in each sequence study group (both basal and post-meal) were compared amongst all groups.
Measured: 6 weeks
Secondary outcomes (2)
Fasting Plasma Glucose 6 Weeks After Therapy
Basal pasma glucose was determined with the glucose oxidase method after each specific 6 week treatment. The absolute values obtained of basal plasma glucose at the end of each 6-week therapeutic period in each sequence study group (both basal and post-meal) were compared amongst all groups.
Measured: 6 weeks
Changes in Plasma Glucose Post-MTT After Each Six Weeks of Therapy Compared to Baseline
The absolute values of mean plasma glucose post-meal (360 minutes)were determined after each specific 6 week treatment and these absolute values after each specific sequence therapy were compared amongst all groups.
Measured: 360 min
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Jan 2009 (estimated)
- Study startOct 2009
- Primary completionJun 2012
- Study completionOct 2012
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for DiabetesStudies of the same condition, open and under way.
- More trials run by The University of Texas Health Science Center at San AntonioThe 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
- Crossover
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 16 participants (actual)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Eugenio Cersosimo, The University of Texas Health Science Center at San Antonio
- Investigators
- Eugenio Cersosimo, MD, Principal investigator, University of TX Health Science Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00820573
- Sponsor's protocol ID
- 35464
- Status last verified
- Dec 2013
- First submitted
- 8 Jan 2009
- Last updated
- 13 Dec 2013
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Publications
Solis-Herrera C, Triplitt C, Garduno-Garcia Jde J, Adams J, DeFronzo RA, Cersosimo E. Mechanisms of glucose lowering of dipeptidyl peptidase-4 inhibitor sitagliptin when used alone or with metformin in type 2 diabetes: a double-tracer study. Diabetes Care. 2013 Sep;36(9):2756-62. doi: 10.2337/dc12-2072. Epub 2013 Apr 11.
PubMed 23579178
Study at a glance
From the registry record, last updated by the sponsor on 13 Dec 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Mechanisms of Glucose Lowering Effects of Sitagliptin and Metformin Alone and in Combination in Patients With Type 2 Diabetes Mellitus
- ClinicalTrials.gov ID
- NCT00820573
- Acronym / sponsor ID
- 35464
- Conditions
- Diabetes
- Keywords
- Diabetes
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 16 participants (actual)
- Lead sponsor
- The University of Texas Health Science Center at San AntonioUniversity, hospital or other
- Study start
- Oct 2009
- Primary completion
- Jun 2012 (actual)
- Study completion
- Oct 2012 (actual)
- First posted
- 12 Jan 2009 (estimated)
- Results
- Posted 13 Dec 2013
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
In patients with type 2 diabetes with inadequate glycemic control on diet and exercise after 6 weeks of treatment:
Objective: To assess the effects of co-administration of sitagliptin and metformin compared to placebo on hepatic glucose production (HGP).
Hypothesis: After 6 weeks of treatment, the co-administration of sitagliptin and metformin provides greater reduction in hepatic glucose production (HGP) compared to placebo.
Detailed description
PRIMARY:
In patients with type 2 diabetes with inadequate glycemic control on diet and exercise after 6 weeks of treatment:
Objective: To assess the effects of co-administration of sitagliptin and metformin compared to placebo on hepatic glucose production (HGP).
Hypothesis: After 6 weeks of treatment, the co-administration of sitagliptin and metformin provides greater reduction in hepatic glucose production (HGP) compared to placebo.
SECONDARY:
In patients with type 2 diabetes with inadequate glycemic control on diet and exercise after 6 weeks of treatment:
- Objective: To assess the effects of co-administration of sitagliptin and metformin compared to placebo on post-meal glucose during meal tolerance test (MTT). Hypothesis: After 6 weeks of treatment the co-administration of sitagliptin and metformin provides greater reduction in the total glucose AUC (0-6 hr) during MTT compared to placebo.
- Objective: To assess the effects of co-administration of sitagliptin and metformin compared to placebo on fasting plasma glucose (FPG). Hypothesis: After 6 weeks of treatment the co-administration of sitagliptin and metformin provides greater reduction in FPG compared to placebo.
- Objective: To assess the effects sitagliptin alone compared to placebo on HGP. Hypothesis: After 6 weeks of treatment, sitagliptin alone provides greater reduction in HGP compared to placebo
EXPLORATORY OBJECTIVES:
(i) Objective: after 6 weeks of treatment, to assess the effects co-administration of sitagliptin and metformin compared to placebo on:
- active and inactive incretin concentrations (fasting and post-meal GLP-1 and fasting and post-meal GIP).
- glucagon concentration (fasting and post-meal).
- parameters of insulin secretion and insulin sensitivity.
- splanchnic glucose uptake. (ii) Objective: after 6 weeks of treatment, to assess the effects co-administration of sitagliptin and metformin compared to treatment with sitagliptin alone and metformin alone on:
- glucose concentration (fasting and total glucose AUC [0-6 hr]).
- active and inactive incretin concentrations (fasting and post-meal GLP-1 and fasting and post-meal GIP).
- glucagon concentration (fasting and post-meal).
- parameters of insulin secretion and insulin sensitivity.
- HGP.
- splanchnic glucose uptake. (iii) Objective: after 6 weeks of treatment, to assess the effects of sitagliptin alone and metformin alone compared to placebo on:
- glucose concentration (fasting and total glucose AUC [0-6 hr]).
- active and inactive incretin concentrations (fasting and post-meal GLP-1 and fasting and post-meal GIP).
- glucagon concentration (fasting and post-meal).
- parameters of insulin secretion and insulin sensitivity.
- HGP.
- splanchnic glucose uptake.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Placebo | Placebo comparator | Drug: PlaceboPlacebo to be provided for 6 weeks |
| Sitagliptin | Experimental | Drug: SitagliptinSitagliptin to be provided for 6 weeks |
| Metformin | Experimental | Drug: MetforminMetformin to be provided for 6 weeks |
| Sitagliptin+Metfromin | Experimental | Drug: Sitagliptin + MetforminSitagliptin + Metformin combined will be provided for 6 weeks |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (21 listed)
- Patients must meet all of the following inclusion criteria to participate in the study.
- Patients with screening values/findings outside ranges described in the protocol may have one repeat determination performed and if the repeat value satisfies the criterion, they may continue in the screening process.
- If the repeat value does not satisfy the criterion, the principal investigator will review the abnormal laboratory value and decide whether the subject may continue in the screening process.
- All screening laboratory measurements are to be performed after an overnight fast ≥10 hours in duration.
- Patients must be able to communicate meaningfully with the investigator and must be legally competent to provide written informed consent.
Key exclusion criteria (8 listed)
- Patients are excluded from participation in the study if they meet any of the following criteria:
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 |
|---|---|---|
| SitagliptinAlso: Januviatablet, 100 mg/day, 6 weeks | Drug | Sitagliptin |
| MetforminAlso: Glucophagetablet, 1000 mg/ bid, 6 weeks | Drug | Metformin |
| Sitagliptin + MetforminAlso: Januvia and glucophagetablet, Sitagliptin (100mg/day) + tablet, Metformin (1000 mg/bid), 6 weeks | Drug | Sitagliptin+Metfromin |
| PlaceboAlso: Placebo tabletPlacebo 6 weeks | Drug | Placebo |
Primary outcome
Objective: Comparisons of the Effects of Co-administration of Sitagliptin and Metformin Alone or in Combination Versus Placebo on Baseline Endogenous Glucose Production (EGP).
Time frame: 6 weeks
Baseline endogenous glucose production prior to a mixed meal tolerance test (placebo) and following 6 weeks of either sitagliptin, metformin or sitagliptin plus metformin combination therapy in all 16 participants
Average of Plasma Glucose During Mixed Meal Tolerance Test (MTT) Compared to Baseline Plasma Glucose to Post Therapy (6-weeks).
Time frame: 6 weeks
The degree of suppression of baseline endogenous glucose production was measured in absolute values and as a percent of basal values at the end of each 6-week therapeutic period. The absolute values obtained in each sequence study group (both basal and post-meal) were compared amongst all groups.
2 secondary outcomes
Fasting Plasma Glucose 6 Weeks After Therapy
Time frame: 6 weeks
Changes in Plasma Glucose Post-MTT After Each Six Weeks of Therapy Compared to Baseline
Time frame: 360 min
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Dec 2013.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 23579178Solis-Herrera C, Triplitt C, Garduno-Garcia Jde J, Adams J, DeFronzo RA, Cersosimo E. Mechanisms of glucose lowering of dipeptidyl peptidase-4 inhibitor sitagliptin when used alone or with metformin in type 2 diabetes: a double-tracer study. Diabetes Care. 2013 Sep;36(9):2756-62. doi: 10.2337/dc12-2072. Epub 2013 Apr 11.
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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.
Eugenio Cersosimo, MD principal investigator
University of TX Health Science Center
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 Sitagliptin, Metformin and Sitagliptin + Metformin in people with Diabetes, run by The University of Texas Health Science Center at San Antonio at 1 site in United States.
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 21 inclusion and 8 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 13 Dec 2013. 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 United States. 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 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?
Yes. Results are posted in the registry (first posted 13 Dec 2013). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Objective: Comparisons of the Effects of Co-administration of Sitagliptin and Metformin Alone or in Combination Versus Placebo on Baseline Endogenous Glucose Production (EGP). (time frame: 6 weeks). The study lists 2 primary outcomes in all. 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 NCT00820573, 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 13 Dec 2013.