Predictive Parameters for Efficacy of Sitagliptin and Metformin Combination

Overview[ - collapse ][ - ]

Purpose It is well established that inhibition of dipeptidyl peptidase (DPP)-IV reduces glucose levels in both fasting and postprandial states and preserves pancreatic beta cell function in patients with type 2 diabetes. Their mechanism of action is derived from increased incretin (GLP-1) levels, which stimulate insulin secretion as well as insulin biosynthesis and inhibit glucagon secretion from pancreas. Recent studies reported that combination therapy with DPP-IV inhibitors and metformin have additive or synergistic effects in lowering glycose level, preserving beta-cell mass and function as well as enhancing insulin sensitivity. However, there have been few studies about the difference of glucose lowering effect of combination therapy of DPP-IV inhibitors and metformin according to the secretory capacity of pancreas. The researchers hypothesized that combination therapy with DPP-IV inhibitor and metformin may have more favorable glucose lowering effect in type 2 diabetic patients who have preserved pancreatic secretory function. The researchers plan to investigate the difference of glucose lowering effect of 24 weeks treatment with sitagliptin (DPP-IV inhibitor) in combination with metformin according to basal c-peptide and glucagon level in type 2 diabetic patients.
ConditionDiabetes
InterventionDrug: sitagliptin, metformin
PhasePhase 4
SponsorSeoul National University Bundang Hospital
Responsible PartySeoul National University Bundang Hospital
ClinicalTrials.gov IdentifierNCT00969566
First ReceivedAugust 31, 2009
Last UpdatedJanuary 5, 2012
Last verifiedJanuary 2012

Tracking Information[ + expand ][ + ]

First Received DateAugust 31, 2009
Last Updated DateJanuary 5, 2012
Start DateJanuary 2009
Estimated Primary Completion DateJuly 2011
Current Primary Outcome MeasuresThe change of HbA1c [Time Frame: 52 weeks] [Designated as safety issue: Yes]
Current Secondary Outcome Measures
  • Fasting Plasma Glucose (FPG) [Time Frame: 52 weeks] [Designated as safety issue: Yes]
  • Postprandial Plasma Glucose (PPG) [Time Frame: 52 weeks] [Designated as safety issue: Yes]
  • C-peptide [Time Frame: 52 weeks] [Designated as safety issue: Yes]
  • Glucagon [Time Frame: 52 weeks] [Designated as safety issue: Yes]
  • Homeostatic model assessment of insulin resistance (HOMA-IR) [Time Frame: 52 weeks] [Designated as safety issue: Yes]

Descriptive Information[ + expand ][ + ]

Brief TitlePredictive Parameters for Efficacy of Sitagliptin and Metformin Combination
Official TitlePredictive Parameters for Therapeutic Efficacy of Initial Combination Therapy With Sitagliptin and Metformin in Type 2 Diabetic Patients
Brief Summary
It is well established that inhibition of dipeptidyl peptidase (DPP)-IV reduces glucose
levels in both fasting and postprandial states and preserves pancreatic beta cell function
in patients with type 2 diabetes. Their mechanism of action is derived from increased
incretin (GLP-1) levels, which stimulate insulin secretion as well as insulin biosynthesis
and inhibit glucagon secretion from pancreas. Recent studies reported that combination
therapy with DPP-IV inhibitors and metformin have additive or synergistic effects in
lowering glycose level, preserving beta-cell mass and function as well as enhancing insulin
sensitivity. However, there have been few studies about the difference of glucose lowering
effect of combination therapy of DPP-IV inhibitors and metformin according to the secretory
capacity of pancreas.

The researchers hypothesized that combination therapy with DPP-IV inhibitor and metformin
may have more favorable glucose lowering effect in type 2 diabetic patients who have
preserved pancreatic secretory function. The researchers plan to investigate the difference
of glucose lowering effect of 24 weeks treatment with sitagliptin (DPP-IV inhibitor) in
combination with metformin according to basal c-peptide and glucagon level in type 2
diabetic patients.
Detailed DescriptionNot Provided
Study TypeInterventional
Study PhasePhase 4
Study DesignAllocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
ConditionDiabetes
InterventionDrug: sitagliptin, metformin
sitagliptin 100mg once daily and metformin 500mg twice daily, orally, for 24 weeks.
Other Names:
Januvia
Study Arm (s)Experimental: Metformin+Sitagliptin
Initial combination of metformin and sitagliptin

Recruitment Information[ + expand ][ + ]

Recruitment StatusCompleted
Estimated Enrollment150
Estimated Completion DateJuly 2011
Estimated Primary Completion DateJune 2010
Eligibility Criteria
Inclusion Criteria:

- Type 2 diabetes

- HbA1c ≥ 7%

- Age ≥ 18

Exclusion Criteria:

- Contraindication to sitagliptin or metformin

- Pregnant or breast feeding women

- Reproductive-age women who refuse contraception

- Type 1 diabetes, gestational diabetes, or diabetes with secondary cause

- Chronic hepatitis B or C (except healthy carrier of HBV), liver disease (AST/ALT >
3-fold the upper limit of normal)

- Renal failure (Cr > 2.0)

- Cancer within 5 years (except squamous cell cancer, cervical cancer, thyroid cancer
with appropriate treatment)

- Not appropriate for oral antidiabetic agent

- Medication which affect glycemic control

- Disease which affect efficacy and safety of drugs

- Other clinical trial within 30 days
GenderBoth
Ages18 Years
Accepts Healthy VolunteersNo
ContactsNot Provided
Location CountriesKorea, Republic of

Administrative Information[ + expand ][ + ]

NCT Number NCT00969566
Other Study ID NumbersSNUBH_ENDO1
Has Data Monitoring CommitteeYes
Information Provided BySeoul National University Bundang Hospital
Study SponsorSeoul National University Bundang Hospital
CollaboratorsNot Provided
Investigators Principal Investigator: Soo Lim, MD, MPH, PHD Seoul National University Bundang Hospital
Verification DateJanuary 2012

Locations[ + expand ][ + ]

Seoul National University Bundang Hospital
Seongnam, Gyeonggi, Korea, Republic of, 463-707