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

Status

Completed

Phases

Phase 4

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01917656

Acronym

LIRA-Ramadan™

Enrollment

343

Registered

2013-08-07

Start date

2014-01-09

Completion date

2014-09-04

Last updated

2017-08-24

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Diabetes, Diabetes Mellitus, Type 2

Brief summary

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).

Interventions

DRUGliraglutide

1.8 mg administered subcutaneously (s.c., under the skin) once daily

DRUGmetformin

Subjects will continue on their pre-trial metformin tablet treatment, dose unchanged

DRUGsulphonylurea

Subjects will continue on their pre-trial SU tablet treatment, doses unchanged

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

NONE

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

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)

Design outcomes

Primary

Measure	Time frame	Description
Change in Fructosamine From Start of Ramadan to End of Ramadan	Day -1, day 29	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).

Secondary

Measure	Time frame	Description
Change From Start of Ramadan to End of Ramadan in Fasting Plasma Glucose (FPG)	Day -1, day 29	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	Baseline, day 29	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)	Baseline, day 29	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	Baseline, day 29	—
Fructosamine at End of Ramadan	Day 29	The fructosamine values at the end of Ramadan (visit 12) were presented
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	Visit 14 (4 weeks post Ramadan)	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.	Day -1 to day 29	—
Number of Treatment Emergent Adverse Events (TEAEs) During Ramadan (Fasting), Based on Each Subject's Individual Fasting Period.	Day -1 to day 29	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
Subjects Who at End of Treatment (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 (Visit 14, 4 weeks post Ramadan) achieve (y/n): HbA1c below 7.0% (53 mmol/mol) (ADA target)

Countries

Algeria, India, Israel, Lebanon, Malaysia, South Africa, United Arab Emirates

Participant flow

Recruitment details

The trial was conducted at 39 sites in 7 countries as follows: Algeria: 7 sites; Israel: 4 sites; India: 5 sites; Lebanon: 2 sites; Malaysia: 7 sites; South Africa: 8 sites; United Arab Emirates: 6 sites

Pre-assignment details

Subjects were randomised in a 1:1 manner to either switch to liraglutide 1.8 mg/day added on to metformin or to continue their pre-trial SU and metformin treatment.

Participants by arm

Arm	Count
Liraglutide and Metformin Liraglutide 1.8 mg administered once daily subcutaneously, in combination with pre-trial tablet metformin of unchanged dose.	171
Sulfonylurea and Metformin Subjects continued on pre-trial sulfonylurea tablet treatment, in combination with pre-trial tablet metformin of unchanged dose.	170
Total	341

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Adverse Event	11	0
Overall Study	Lost to Follow-up	3	4
Overall Study	Unclassified	0	3
Overall Study	Withdrawal by Subject	4	3
Overall Study	Withdrawal criteria	8	14

Baseline characteristics

Characteristic	Liraglutide and Metformin	Sulfonylurea and Metformin	Total
Age, Continuous	54.9 years STANDARD_DEVIATION 9.27	54.0 years STANDARD_DEVIATION 9.33	54.5 years STANDARD_DEVIATION 9.3
Sex: Female, Male Female	86 Participants	87 Participants	173 Participants
Sex: Female, Male Male	85 Participants	83 Participants	168 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	— / —	— / —
other Total, other adverse events	8 / 152	1 / 163
serious Total, serious adverse events	2 / 152	0 / 163

Outcome results

Primary

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).

Time frame: Day -1, day 29