Effects of Sitagliptin on Type 2 Diabetes Mellitus Patients on Treatment With Metformin and Insulin

Open-labelled, Randomized, Active-controlled, Parallel-arm, Single-center Study on Effect of Sitagliptin on T2DM Patients on Treatment With Metformin and Insulin

The purpose of the study is to determine the efficacy and safety of sitaglipin in the treatment of Type 2 diabetes mellitus (T2DM) patients with inadequate glycemic control using metformin and insulin.

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus, Type 2
• Intervention / Treatment: Drug: Sitagliptin; Drug: Glimepiride; Drug: Metformin; Drug: Insulin

Detailed Description

DPP-4 inhibitors enhance function of endogenous incretin that helps with glucose homoeostasis. DPP-4 inhibitors have been proved to promote glycemic control without increasing risk of hypoglycemia and weight gain. In addition, they may improve beta-cell function and do not have any known associations with overt cardiovascular or hepatic safety risks.

Addition of sitagliptin to treatment of T2DM patients poorly controlled on insulin +/- metformin has been shown to reduce HbA1c while being generally well-tolerated.

It could be clinically useful to add sitaglipin to treatment regimen of T2DM patients on stable therapy with insulin & metformin. Apart from glycemic reduction, secondary effects like prevention of weight gain, reduction in insulin dose, improved cardiovascular risk profile, etc. may be expected from addition of sitagliptin to treatment.

• Study Type: Interventional
• Enrollment (Actual): 440
• Phase: Phase 4

Contacts and Locations

Study Locations

• India
  • Kerala
    • Thiruvananthapuram, Kerala, India, 695032
      • Jothydev's Diabetes and Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 25 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• T2DM patients on metformin and biphasic or basal regimens of insulin
• HbA1c ≥7.3% to ≤8.5%
• Age: 25 to 60 yrs
• Insulin TDD > 10 IU

Exclusion Criteria:

• Use of acarbose, pioglitazone or short-acting insulin analogues at time of run-in phase
• History of type 1 diabetes mellitus
• Creatinine clearance ≤50 mL/min
• Chronic liver & kidney diseases, SGOT/PT≥2.5x upper limit of normal, uncontrolled thyroid disorders , cardiac failure, hemochromatosis, autoimmune disorders, corticosteroid intake.
• BMI >40 kg/m2

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Sitagliptin along with metformin and insulin	Drug: Sitagliptin; 100 mg once daily for 6 months; Drug: Glimepiride; 1 mg/2 mg/3 mg once daily; Drug: Metformin; >=1000 mg twice daily; Drug: Insulin; TDD > 10 IU once/twice daily
Active Comparator: Glimepiride as an active comparator to Sitagliptin	Drug: Sitagliptin; 100 mg once daily for 6 months; Drug: Glimepiride; 1 mg/2 mg/3 mg once daily; Drug: Metformin; >=1000 mg twice daily; Drug: Insulin; TDD > 10 IU once/twice daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Reduction in HbA1c from baseline	To confirm the efficacy of metformin+ insulin+ sitagliptin in controlling glycemia with respect to change from baseline in HbA1c after 24 weeks of administration. This will be accomplished by comparing the difference in change from baseline in HbA1c after 24 weeks of administration, compared with metformin+insulin+glimepiride to a non-inferiority limit of 0.3% , and if non-inferiority is proven, to a superiority limit of 0%.	six months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in total daily dose (TDD) of insulin	Change from baseline in insulin TDD (30-day geometric mean) at Month 6	6 months
Episodes of hypoglycemia	Hypoglycemia (Total, severe, nocturnal) (From Month 0 to Month 6), as assessed by questionnaire and supplemented by SMBG values, if available	6 months
Proportion of patients with HbA1c reduction	Proportion of patients, who completed treatment , with HbA1c value <6.5% & ≤7.3% at end of study (Month 6)	6 months
change in weight and BMI		6 months
Change in both HbA1c and TDD	Proportion of patients achieving both HbA1c ≤6.5% AND reduction in TDD (total daily dose of insulin)	6 months
Change in insulin resistance and beta cell function	Change from baseline in c-peptide levels, homeostasis model assessments of β-cell function and insulin resistance (HOMA-β and HOMA-IR)	6 months
Change in lipid profile from baseline		6 months

Collaborators and Investigators

• Sponsor: Jothydev's Diabetes and Research Centre
• Investigators: Principal Investigator: Jothydev Kesavadev, MD, Jothydev's Diabetes and Research Center

Study record dates

Study Major Dates

• Study Start: February 1, 2012
• Primary Completion (Actual): May 1, 2014
• Study Completion (Actual): May 1, 2014

Study Registration Dates

• First Submitted: April 23, 2011
• First Submitted That Met QC Criteria: April 25, 2011
• First Posted (Estimate): April 26, 2011

Study Record Updates

• Last Update Posted (Estimate): May 30, 2014
• Last Update Submitted That Met QC Criteria: May 29, 2014
• Last Verified: May 1, 2014

More Information

Terms related to this study

• Keywords: Insulin; Diabetes Mellitus, Type 2; Sitagliptin
• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Enzyme Inhibitors; Immunosuppressive Agents; Immunologic Factors; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Protease Inhibitors; Incretins; Dipeptidyl-Peptidase IV Inhibitors; Metformin; Sitagliptin Phosphate; Glimepiride
• Other Study ID Numbers: JDC/SITA/021/2011