Mechanisms of Glucose Lowering Effects of Sitagliptin and Metformin Alone and in Combination in Patients With T2DM

NCT00820573 | Completed Phase 4 Results

• 1 other identifier: 35464
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief 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). Hypothesis: After 6 weeks of treatment, the co-administration of sitagliptin and metformin provides greater reduction in hepatic glucose production (HGP) compared to placebo.

Conditions

Diabetes

Keywords

Diabetes

Outcome Measures

Primary Outcomes (2)

• 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

  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.

  6 weeks

Secondary Outcomes (2)

• Fasting Plasma Glucose 6 Weeks After Therapy

  6 weeks

• Changes in Plasma Glucose Post-MTT After Each Six Weeks of Therapy Compared to Baseline

  360 min

Study Arms (4)

Placebo

PLACEBO COMPARATOR

Placebo to be provided for 6 weeks

Drug: Placebo

Sitagliptin

EXPERIMENTAL

Sitagliptin to be provided for 6 weeks

Drug: Sitagliptin

Metformin

EXPERIMENTAL

Metformin to be provided for 6 weeks

Drug: Metformin

Sitagliptin+Metfromin

EXPERIMENTAL

Sitagliptin + Metformin combined will be provided for 6 weeks

Drug: Sitagliptin + Metformin

Interventions

Sitagliptin DRUG

tablet, 100 mg/day, 6 weeks

Also known as: Januvia

Sitagliptin

Metformin DRUG

tablet, 1000 mg/ bid, 6 weeks

Also known as: Glucophage

Metformin

Sitagliptin + Metformin DRUG

tablet, Sitagliptin (100mg/day) + tablet, Metformin (1000 mg/bid), 6 weeks

Also known as: Januvia and glucophage

Sitagliptin+Metfromin

Placebo DRUG

Placebo 6 weeks

Also known as: Placebo tablet

Placebo

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• The University of Texas Health Science Center at San Antonio: lead

Study Sites (1)

Texas Diabetes Institute

San Antonio, Texas, 78207, United States

Location

Related Publications (1)

• 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.

  PMID: 23579178 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus

Interventions

Sitagliptin Phosphate; Metformin

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrazines; Biguanides; Guanidines; Amidines; Organic Chemicals

Results Point of Contact

• Title: Eugenio Cersosimo, MD PhD
• Organization: University of Texas HSC at San Antonio

Eugenio.cersosimo@uhs-sa.com

210 358 7200

Study Officials

• Eugenio Cersosimo, MD

  University of TX Health Science Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor Medicine

Study Record Dates

• First Submitted: January 8, 2009
• First Posted: January 12, 2009
• Study Start: October 1, 2009
• Primary Completion: June 1, 2012
• Study Completion: October 1, 2012
• Last Updated: December 13, 2013
• Results First Posted: December 13, 2013

Record last verified: 2013-12

Locations

US (1)