Short Term Effect of Liraglutide Versus Vildagliptine on Insulin Secretion and Insulin Sensitivity in Type 2 Diabetes

Study Overview
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Brief Summary
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This is a single blind randomised controlled clinical trial in uncontrolled type 2 Diabetes mellitus patients on oral glucose lowering agents, and naive to incretinomimetic. Participants will be randomised in two Arms : arm 1 receiving Liraglutide at 1,2 mg/day and arm 2 Vildagliptine at 100mg/day over 14 days. The two arms will be compared for 14-day changes in insulin secretion and insulin sensitivity.

Detailed Description
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Incretinomimetics include exogenous Glucagon-Like Peptide analogs (GLP1a) such as Liraglutide, and inhibitors of Dipeptidyl peptidase IV (DPP4i) that prolong the half-life of endogenous GLP1 such as Vildagliptin. It remains unclear which of the two strategies (exogenous GLP1 or prolonging half-life of endogenous GLP1) have better short term effect on insulin sensitivity and insulin secretion in people living with type 2 diabetes. This study aims to investigate the short-term metabolic effects of a GLP-1 analog Liraglutide versus a DPP4i Vildagliptin. It is a randomized, controlled, single-blinded clinical trial. Study population consists of uncontrolled type 2 diabetes mellitus patients (HbA1c≥7%) under mono or bi oral anti-diabetic therapy, naïve of any incretinomimetic treatment. Participants are randomized in 2 arms. The intervention in arm 1 consists of add-on subcutaneous Liraglutide at 0.6mg/day for 1 week increased to 1.2mg the second week. In the second arm, it consists of oral Vildagliptine at 100mg daily for two weeks. The primary outcome is the variation in euglycaemic hyperinsulinaemic clamp-derived insulin sensitivity before randomization and the day after intervention, secondary outcomes include 14-day changes in insulin secretion during a mixed meal tolarance test, body weight and body composition, and an indirect calorimetry measured resting energy expenditure. Changes from baseline to 14 days in serum creatinine and alanine amino transferase, C-reactive protein and lipid profile will also be recorded.

Official Title
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Short Term Effect of Liraglutide Versus Vildagliptine on Insulin Secretion and Insulin Sensitivity in a Sub Saharan African Population With Type 2 Diabetes

Conditions
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Type 2 Diabetes Mellitus

Intervention / Treatment
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* Drug: sub cutaneous liraglutide
* Drug: Oral Vildagliptin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Type 2 diabetes mellitus known for at least one year Uncontrolled glycaemic profile with HbA1c ≥ 7% on oral antidiabetic mono or bi-therapy Naïve of incretinomimetic treatment Informed consent Exclusion Criteria: Change in antidiabetic treatment less than 3 months prior to inclusion Pancreatitis Alanine amino transferase > 3 times the normal values Pregnant or breastfeeding women Estimated glomerular filtration rate < 60ml/min Infection less than 10 days prior to inclusion or during the study Acute complication of diabetes Total haemoglobin < 11g/dL in women or < 13g/dL in men Withdrawal of consent

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 70 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: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: sub cutaneous liraglutide<br>once daily add-on subcutaneous injection of Liraglutide at 0.6mg/day for 1 week increased to 1.2mg the second week | Drug: sub cutaneous liraglutide<br>* Liraglutide 1.2mg/day<br>* Other names: Victoza;|
| Active Comparator: Oral Vildagliptin<br>Once daily oral 100mg of Vildagliptine for two weeks | Drug: Oral Vildagliptin<br>* Vildagliptin 50mg/day<br>* Other names: Galvus;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Insulin sentivity | 2-week change in clamp-measured insulin sensitivity | 2 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| insulin secretion | 2-week change in meal test measured insulin secretion | 2 weeks | 
| lipid profile | 2-week change in fasting serum lipids | 2 weeks | 
| body weight | 2-week change in body weight | 2 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Diabetes, GLP-1, Insulin secretion, insulin sensitivity, Africa, Liraglutide, Vildaglipin