Efficacy and Safety of Liraglutide Versus Sulphonylurea Both in Combination With Metformin During Ramadan in Subjects With Type 2 Diabetes

Study Overview
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Brief Summary
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This trial is conducted in Africa and Asia. The aim of the trial is to investigate the efficacy and safety of liraglutide versus sulphonylurea (SU) both in combination with metformin during Ramadan in subjects with type 2 diabetes (T2DM).

Official Title
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Efficacy and Safety of Liraglutide Versus Sulphonylurea Both in Combination With Metformin During Ramadan in Subjects With Type 2 Diabetes

Conditions
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Diabetes, Diabetes Mellitus, Type 2

Intervention / Treatment
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* Drug: liraglutide
* Drug: metformin
* Drug: sulphonylurea


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: - Subjects diagnosed with T2DM and treated with metformin equal to or above 1000 mg/day and SU (gliclazide, glipizide or glyburide/glibenclamide at maximum tolerated dose (at least half maximum approved dose) or glimepiride at maximum tolerated dose (at least 2 mg/day)), both at a stable dose for at least 90 days prior to screening. Stable is defined as unchanged medication and dose - HbA1c 7.0-10.0% (53- 86 mmol/mol) (both inclusive) - Body Mass Index (BMI) equal to or above 20 kg/m^2 - Subjects who have expressed their intention to fast (daytime, i.e. between sunrise and sunset) during Ramadan after receiving medical counselling regarding the risk of fasting Exclusion Criteria: - Any contraindication for successful and sustained fasting from a medical perspective at the discretion of the investigator (such as acute illness, severe hypoglycaemia within 90 days prior to screening, a history of recurrent hypoglycaemia, hypoglycaemia unawareness, ketoacidosis within 90 days prior to screening, hyperosmolar hyperglycaemic coma within 90 days prior to screening, subjects performing intense physical labour) - Any chronic disorder or severe disease which, in the opinion of the investigator might jeopardise subject's safety or compliance with the protocol - History of chronic pancreatitis or idiopathic acute pancreatitis - Screening calcitonin value equal to or above 50 ng/L - Personal or family history of medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia syndrome type 2 (MEN 2) - Impaired liver function, defined as alanine aminotransferase (ALAT) equal to or above 2.5 times upper normal limit (UNL) - Impaired renal function defined as estimated glomerular filtration rate (eGFR) below 60 mL/min/1.73 m^2 per Modification of Diet in Renal Disease (MDRD) formula) - Any episode of unstable angina, acute coronary event, cerebral stroke/transient ischemic attack (TIA) or other significant cardiovascular event as judged by the investigator within 90 days prior to screening - Diagnosis of malignant neoplasm in the previous 5 years (except basal cell skin cancer or squamous cell skin cancer)

Ages Eligible for Study
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Minimum Age: 18 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: Liraglutide+Metformin<br>Liraglutide 1.8 mg administered once daily subcutaneously, in combination with pre-trial tablet metformin of unchanged dose. | Drug: liraglutide<br>* 1.8 mg administered subcutaneously (s.c., under the skin) once daily<br>Drug: metformin<br>* Subjects will continue on their pre-trial metformin tablet treatment, dose unchanged<br>|
| Active Comparator: Sulphonylurea and Metformin<br>Subjects continued on pre-trial sulphonylurea tablet treatment, in combination with pre-trial tablet metformin of unchanged dose. | Drug: metformin<br>* Subjects will continue on their pre-trial metformin tablet treatment, dose unchanged<br>Drug: sulphonylurea<br>* Subjects will continue on their pre-trial SU tablet treatment, doses unchanged<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Fructosamine From Start of Ramadan to End of Ramadan | The level of fructosamine in the blood was used to assess the glycaemic control in the patients during the time period described- from start of Ramadan (day -1, visit 8) to end of Ramadan (day 29, visit 12). | Day -1, day 29 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fructosamine at End of Ramadan | The fructosamine values at the end of Ramadan (visit 12) were presented | Day 29 | 
| Change From Start of Ramadan to End of Ramadan in Fasting Plasma Glucose (FPG) | The level of FPG in the blood of fasting patients was addressed to monitor glycaemic control during the period described. | Day -1, day 29 | 
| Change From Baseline to End of Ramadan in Fasting Plasma Glucose | The changes from baseline measured postbaseline (i.e., the changes measured on visit 8 and 12) entered as the dependent variables, and visit, treatment, country, and the stratification variables were included as fixed factors and the corresponding values for the specific endpoint measured at randomisation as covariate. | Baseline, day 29 | 
| Change From Baseline to End of Ramadan in Glycosylated Haemoglobin (HbA1c) | The level of glycosylated haemoglobin in blood was used to assess the glycaemic control of the patients during the time period described. | Baseline, day 29 | 
| Change From Baseline to End of Ramadan in Body Weight |  | Baseline, day 29 | 
| Subjects Who at End of Treatment (4 Weeks Post Ramadan) Achieve (y/n): HbA1c Below 7.0% (53 mmol/Mol) (ADA Target) | Subjects who at end of treatment (Visit 14, 4 weeks post Ramadan) achieve (y/n): HbA1c below 7.0% (53 mmol/mol) (ADA target) | Visit 14 (4 weeks post Ramadan) | 
| Subjects Who at End of Treatment (4 Weeks Post Ramadan) Achieve (y/n): HbA1c Below 7.0% (53 mmol/Mol), and no Confirmed Hypoglycaemic Episodes | Subjects who at end of treatment (Visit 14, 4 weeks post Ramadan) achieve (y/n): HbA1c below 7.0% (53 mmol/mol) (ADA target) | Visit 14 (4 weeks post Ramadan) | 
| Number of Confirmed Hypoglycaemic Episodes During Ramadan (Fasting), Based on Each Subject's Individual Fasting Period. |  | Day -1 to day 29 | 
| Number of Treatment Emergent Adverse Events (TEAEs) During Ramadan (Fasting), Based on Each Subject's Individual Fasting Period. | A serious AE was an experience that at any dose resulted in any of the following: Death, a life-threatening experience, in-patient hospitalisation or prolongation of existing hospitalisation, a persistent or significant disability or incapacity, congenital anomaly or birth defect, important medical events. Mild - no or transient symptoms, no interference with the subject's daily activities Moderate - marked symptoms, moderate interference with the subject's daily activities Severe - considerable interference with the subject's daily activities, unacceptable | Day -1 to day 29 |