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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Diabetes Mellitus, Type 2

Intervention / Treatment
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* Drug: Sitagliptin
* Drug: Glimepiride
* Drug: Metformin
* Drug: Insulin


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 25 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

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

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Diabetes Mellitus, Type 2, Sitagliptin, Insulin