Efficacy and Safety of Liraglutide Versus Sulphonylurea Both in Combination With Metformin During Ramadan in Subjects With Type 2 Diabetes (LIRA-Ramadan™)

• Fructosamine at End of Ramadan [ Time Frame: Day 29 ] [ Designated as safety issue: No ]
  The fructosamine values at the end of Ramadan (visit 12) were presented
• Change From Start of Ramadan to End of Ramadan in Fasting Plasma Glucose (FPG) [ Time Frame: Day -1, day 29 ] [ Designated as safety issue: No ]
  The level of FPG in the blood of fasting patients was addressed to monitor glycaemic control during the period described.
• Change From Baseline to End of Ramadan in Fasting Plasma Glucose [ Time Frame: Baseline, day 29 ] [ Designated as safety issue: No ]
  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.
• Change From Baseline to End of Ramadan in Glycosylated Haemoglobin (HbA1c) [ Time Frame: Baseline, day 29 ] [ Designated as safety issue: No ]
  The level of glycosylated haemoglobin in blood was used to assess the glycaemic control of the patients during the time period described.
• Change From Baseline to End of Ramadan in Body Weight [ Time Frame: Baseline, day 29 ] [ Designated as safety issue: No ]
• Subjects Who at End of Treatment (4 Weeks Post Ramadan) Achieve (y/n): HbA1c Below 7.0% (53 mmol/Mol) (ADA Target) [ Time Frame: Visit 14 (4 weeks post Ramadan) ] [ Designated as safety issue: No ]
  Subjects who at end of treatment (Visit 14, 4 weeks post Ramadan) achieve (y/n): HbA1c below 7.0% (53 mmol/mol) (ADA target)
• 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 [ Time Frame: Visit 14 (4 weeks post Ramadan) ] [ Designated as safety issue: No ]
  Subjects who at end of treatment (Visit 14, 4 weeks post Ramadan) achieve (y/n): HbA1c below 7.0% (53 mmol/mol) (ADA target)
• Number of Confirmed Hypoglycaemic Episodes During Ramadan (Fasting), Based on Each Subject's Individual Fasting Period. [ Time Frame: Day -1 to day 29 ] [ Designated as safety issue: No ]
• Number of Treatment Emergent Adverse Events (TEAEs) During Ramadan (Fasting), Based on Each Subject's Individual Fasting Period. [ Time Frame: Day -1 to day 29 ] [ Designated as safety issue: No ]

  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

• Fructosamine at End of Ramadan [ Time Frame: Day 29 ] [ Designated as safety issue: No ]
• Change From Start of Ramadan to End of Ramadan in Fasting Plasma Glucose (FPG) [ Time Frame: Day -1, day 29 ] [ Designated as safety issue: No ]
• Change from baseline to end of Ramadan in FPG [ Time Frame: Baseline, day 29 ] [ Designated as safety issue: No ]
• Change From Baseline to End of Ramadan in Glycosylated Haemoglobin (HbA1c) [ Time Frame: Baseline, day 29 ] [ Designated as safety issue: No ]
• Change From Baseline to End of Ramadan in Body Weight [ Time Frame: Baseline, day 29 ] [ Designated as safety issue: No ]
• Subjects Who at End of Treatment (4 Weeks Post Ramadan) Achieve (y/n): HbA1c Below 7.0% (53 mmol/Mol) (ADA Target) [ Time Frame: Day 29 ] [ Designated as safety issue: No ]
• 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 [ Time Frame: Day 29 ] [ Designated as safety issue: No ]
• Number of confirmed hypoglycaemic episodes [ Time Frame: Day -1 to day 29 ] [ Designated as safety issue: No ]
• Number of treatment emergent adverse events (TEAEs) [ Time Frame: Day -1 to day 29 ] [ Designated as safety issue: No ]

• Diabetes
• Diabetes Mellitus, Type 2

• Drug: liraglutide
  1.8 mg administered subcutaneously (s.c., under the skin) once daily
• Drug: metformin
  Subjects will continue on their pre-trial metformin tablet treatment, dose unchanged
• Drug: sulfonylurea
  Subjects will continue on their pre-trial SU tablet treatment, doses unchanged

• Experimental: Liraglutide+Metformin
  Liraglutide 1.8 mg administered once daily subcutaneously, in combination with pre-trial tablet metformin of unchanged dose.
  Interventions:

  • Drug: liraglutide
  • Drug: metformin
• Active Comparator: Sulfonylurea and Metformin
  Subjects continued on pre-trial sulfonylurea tablet treatment, in combination with pre-trial tablet metformin of unchanged dose.
  Interventions:

  • Drug: metformin
  • Drug: sulfonylurea

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)