Trial Outcomes & Findings for Efficacy and Safety of Liraglutide Versus Sulphonylurea Both in Combination With Metformin During Ramadan in Subjects With Type 2 Diabetes (NCT NCT01917656)

NCT ID: NCT01917656

Last Updated: 2017-08-24

Results Overview

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).

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 343 participants
• Primary outcome timeframe: Day -1, day 29
• Results posted on: 2017-08-24

Participant Flow

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

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.

Participant milestones

Measure	Liraglutide and Metformin Liraglutide 1.8 mg administered once daily subcutaneously, in combination with pre-trial tablet metformin of unchanged dose.	Sulfonylurea and Metformin Subjects continued on pre-trial sulfonylurea tablet treatment, in combination with pre-trial tablet metformin of unchanged dose.
Overall Study STARTED	172	171
Overall Study Exposed	171	170
Overall Study Exposed During Ramadan (Fasting)	152	163
Overall Study COMPLETED	146	147
Overall Study NOT COMPLETED	26	24

Reasons for withdrawal

Measure	Liraglutide and Metformin Liraglutide 1.8 mg administered once daily subcutaneously, in combination with pre-trial tablet metformin of unchanged dose.	Sulfonylurea and Metformin Subjects continued on pre-trial sulfonylurea tablet treatment, in combination with pre-trial tablet metformin of unchanged dose.
Overall Study Adverse Event	11	0
Overall Study Withdrawal criteria	8	14
Overall Study Unclassified	0	3
Overall Study Withdrawal by Subject	4	3
Overall Study Lost to Follow-up	3	4

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	Liraglutide and Metformin n=171 Participants Liraglutide 1.8 mg administered once daily subcutaneously, in combination with pre-trial tablet metformin of unchanged dose.	Sulfonylurea and Metformin n=170 Participants Subjects continued on pre-trial sulfonylurea tablet treatment, in combination with pre-trial tablet metformin of unchanged dose.	Total n=341 Participants Total of all reporting groups
Age, Continuous	54.9 years STANDARD_DEVIATION 9.27 • n=5 Participants	54.0 years STANDARD_DEVIATION 9.33 • n=7 Participants	54.5 years STANDARD_DEVIATION 9.30 • n=5 Participants
Sex: Female, Male Female	86 Participants n=5 Participants	87 Participants n=7 Participants	173 Participants n=5 Participants
Sex: Female, Male Male	85 Participants n=5 Participants	83 Participants n=7 Participants	168 Participants n=5 Participants

PRIMARY outcome

Timeframe: Day -1, day 29

Population: Full analysis set (FAS). The number of subjects in FAS were 171 (Liraglutide) and 169 (Sulfonylurea), few subjects did not contribute to this analysis.

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).

Outcome measures

Measure	Liraglutide and Metformin n=146 Participants Liraglutide 1.8 mg administered once daily subcutaneously, in combination with pre-trial tablet metformin of unchanged dose.	Sulfonylurea and Metformin n=151 Participants Subjects continued on pre-trial sulfonylurea tablet treatment, in combination with pre-trial tablet metformin of unchanged dose.
Change in Fructosamine From Start of Ramadan to End of Ramadan	-13.2 umol/L Standard Deviation 36.0	-14.9 umol/L Standard Deviation 43.0

SECONDARY outcome

Timeframe: Day 29

Population: Full analysis set (FAS). The number of subjects in FAS were 171 (Liraglutide) and 169 (Sulfonylurea), few subjects did not contribute to this analysis.

The fructosamine values at the end of Ramadan (visit 12) were presented

Outcome measures

Measure	Liraglutide and Metformin n=146 Participants Liraglutide 1.8 mg administered once daily subcutaneously, in combination with pre-trial tablet metformin of unchanged dose.	Sulfonylurea and Metformin n=151 Participants Subjects continued on pre-trial sulfonylurea tablet treatment, in combination with pre-trial tablet metformin of unchanged dose.
Fructosamine at End of Ramadan	276.8 umol/L Standard Deviation 44.1	284.9 umol/L Standard Deviation 46.6

SECONDARY outcome

Timeframe: Day -1, day 29

Population: Full analysis set (FAS). The number of subjects in FAS were 171 (Liraglutide) and 169 (Sulfonylurea), few subjects did not contribute to this analysis.

The level of FPG in the blood of fasting patients was addressed to monitor glycaemic control during the period described.

Outcome measures

Measure	Liraglutide and Metformin n=146 Participants Liraglutide 1.8 mg administered once daily subcutaneously, in combination with pre-trial tablet metformin of unchanged dose.	Sulfonylurea and Metformin n=157 Participants Subjects continued on pre-trial sulfonylurea tablet treatment, in combination with pre-trial tablet metformin of unchanged dose.
Change From Start of Ramadan to End of Ramadan in Fasting Plasma Glucose (FPG)	-0.1 mmol/L Standard Deviation 2.0	0.1 mmol/L Standard Deviation 3.8

SECONDARY outcome

Timeframe: Baseline, day 29

Population: Full analysis set (FAS). The number of subjects in FAS were 171 (Liraglutide) and 169 (Sulfonylurea), few subjects did not contribute to this analysis.

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.

Outcome measures

Measure	Liraglutide and Metformin n=143 Participants Liraglutide 1.8 mg administered once daily subcutaneously, in combination with pre-trial tablet metformin of unchanged dose.	Sulfonylurea and Metformin n=156 Participants Subjects continued on pre-trial sulfonylurea tablet treatment, in combination with pre-trial tablet metformin of unchanged dose.
Change From Baseline to End of Ramadan in Fasting Plasma Glucose	-1.8 mmol/L Standard Deviation 3.1	-0.6 mmol/L Standard Deviation 3.6

SECONDARY outcome

Timeframe: Baseline, day 29

Population: Full analysis set (FAS). The number of subjects in FAS were 171 (Liraglutide) and 169 (Sulfonylurea), few subjects did not contribute to this analysis.

The level of glycosylated haemoglobin in blood was used to assess the glycaemic control of the patients during the time period described.

Outcome measures

Measure	Liraglutide and Metformin n=146 Participants Liraglutide 1.8 mg administered once daily subcutaneously, in combination with pre-trial tablet metformin of unchanged dose.	Sulfonylurea and Metformin n=156 Participants Subjects continued on pre-trial sulfonylurea tablet treatment, in combination with pre-trial tablet metformin of unchanged dose.
Change From Baseline to End of Ramadan in Glycosylated Haemoglobin (HbA1c)	-1.3 Percent (%) glycosylated haemoglobin Standard Deviation 1.1	-0.7 Percent (%) glycosylated haemoglobin Standard Deviation 0.9

SECONDARY outcome

Timeframe: Baseline, day 29

Population: Full analysis set (FAS). The number of subjects in FAS were 171 (Liraglutide) and 169 (Sulfonylurea), few subjects did not contribute to this analysis.

Outcome measures

Measure	Liraglutide and Metformin n=165 Participants Liraglutide 1.8 mg administered once daily subcutaneously, in combination with pre-trial tablet metformin of unchanged dose.	Sulfonylurea and Metformin n=168 Participants Subjects continued on pre-trial sulfonylurea tablet treatment, in combination with pre-trial tablet metformin of unchanged dose.
Change From Baseline to End of Ramadan in Body Weight	-5.40 kg Standard Error 0.2205	-1.46 kg Standard Error 0.2139

SECONDARY outcome

Timeframe: Visit 14 (4 weeks post Ramadan)

Population: Full analysis set

Subjects who at end of treatment (Visit 14, 4 weeks post Ramadan) achieve (y/n): HbA1c below 7.0% (53 mmol/mol) (ADA target)

Outcome measures

Measure	Liraglutide and Metformin n=171 Participants Liraglutide 1.8 mg administered once daily subcutaneously, in combination with pre-trial tablet metformin of unchanged dose.	Sulfonylurea and Metformin n=169 Participants Subjects continued on pre-trial sulfonylurea tablet treatment, in combination with pre-trial tablet metformin of unchanged dose.
Subjects Who at End of Treatment (4 Weeks Post Ramadan) Achieve (y/n): HbA1c Below 7.0% (53 mmol/Mol) (ADA Target)	51.0 percentage (%) of subjects	29.9 percentage (%) of subjects

SECONDARY outcome

Timeframe: Visit 14 (4 weeks post Ramadan)

Population: Full analysis set

Subjects who at end of treatment (Visit 14, 4 weeks post Ramadan) achieve (y/n): HbA1c below 7.0% (53 mmol/mol) (ADA target)

Outcome measures

Measure	Liraglutide and Metformin n=171 Participants Liraglutide 1.8 mg administered once daily subcutaneously, in combination with pre-trial tablet metformin of unchanged dose.	Sulfonylurea and Metformin n=169 Participants Subjects continued on pre-trial sulfonylurea tablet treatment, in combination with pre-trial tablet metformin of unchanged dose.
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	47.6 percentage (%) of subjects	25.2 percentage (%) of subjects

SECONDARY outcome

Timeframe: Day -1 to day 29

Population: Safety analysis set

Outcome measures

Measure	Liraglutide and Metformin n=152 Participants Liraglutide 1.8 mg administered once daily subcutaneously, in combination with pre-trial tablet metformin of unchanged dose.	Sulfonylurea and Metformin n=163 Participants Subjects continued on pre-trial sulfonylurea tablet treatment, in combination with pre-trial tablet metformin of unchanged dose.
Number of Confirmed Hypoglycaemic Episodes During Ramadan (Fasting), Based on Each Subject's Individual Fasting Period.	246 Events/1000 years of patient exposure	623 Events/1000 years of patient exposure

SECONDARY outcome

Timeframe: Day -1 to day 29

Population: Safety analysis set

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

Outcome measures

Measure	Liraglutide and Metformin n=152 Participants Liraglutide 1.8 mg administered once daily subcutaneously, in combination with pre-trial tablet metformin of unchanged dose.	Sulfonylurea and Metformin n=163 Participants Subjects continued on pre-trial sulfonylurea tablet treatment, in combination with pre-trial tablet metformin of unchanged dose.
Number of Treatment Emergent Adverse Events (TEAEs) During Ramadan (Fasting), Based on Each Subject's Individual Fasting Period. Adverse events	5258 Events/1000 years of patient exposure	3349 Events/1000 years of patient exposure
Number of Treatment Emergent Adverse Events (TEAEs) During Ramadan (Fasting), Based on Each Subject's Individual Fasting Period. Serious adverse events	164 Events/1000 years of patient exposure	0 Events/1000 years of patient exposure
Number of Treatment Emergent Adverse Events (TEAEs) During Ramadan (Fasting), Based on Each Subject's Individual Fasting Period. Severe adverse events	411 Events/1000 years of patient exposure	78 Events/1000 years of patient exposure
Number of Treatment Emergent Adverse Events (TEAEs) During Ramadan (Fasting), Based on Each Subject's Individual Fasting Period. Moderate adverse event	986 Events/1000 years of patient exposure	779 Events/1000 years of patient exposure
Number of Treatment Emergent Adverse Events (TEAEs) During Ramadan (Fasting), Based on Each Subject's Individual Fasting Period. Mild adverse event	3861 Events/1000 years of patient exposure	2492 Events/1000 years of patient exposure

Adverse Events

Liraglutide and Metformin

Serious events: 2 serious events

Other events: 8 other events

Deaths: 0 deaths

Sulfonylurea and Metformin

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Serious adverse events

Measure	Liraglutide and Metformin n=152 participants at risk Liraglutide 1.8 mg administered once daily subcutaneously, in combination with pre-trial tablet metformin of unchanged dose.	Sulfonylurea and Metformin n=163 participants at risk Subjects continued on pre-trial sulfonylurea tablet treatment, in combination with pre-trial tablet metformin of unchanged dose.
Infections and infestations Abscess limb	0.66% 1/152 • Number of events 1 • A treatment emergent AE during Ramadan (fasting) had onset on or after the individual subject's first day of Ramadan fasting, and no later than the individual subject's last day of Ramadan fasting. Safety analysis set included all randomised subjects who were exposed to the trial drug. Subjects in the safety analysis set contributed to the evaluation 'as treated'. A total of 315 randomised subjects were exposed to trial products during Ramadan (fasting), of which 152 subjects were exposed to liraglutide and 163 subjects were exposed to SU.	0.00% 0/163 • A treatment emergent AE during Ramadan (fasting) had onset on or after the individual subject's first day of Ramadan fasting, and no later than the individual subject's last day of Ramadan fasting. Safety analysis set included all randomised subjects who were exposed to the trial drug. Subjects in the safety analysis set contributed to the evaluation 'as treated'. A total of 315 randomised subjects were exposed to trial products during Ramadan (fasting), of which 152 subjects were exposed to liraglutide and 163 subjects were exposed to SU.
Infections and infestations Gastroenteritis	0.66% 1/152 • Number of events 1 • A treatment emergent AE during Ramadan (fasting) had onset on or after the individual subject's first day of Ramadan fasting, and no later than the individual subject's last day of Ramadan fasting. Safety analysis set included all randomised subjects who were exposed to the trial drug. Subjects in the safety analysis set contributed to the evaluation 'as treated'. A total of 315 randomised subjects were exposed to trial products during Ramadan (fasting), of which 152 subjects were exposed to liraglutide and 163 subjects were exposed to SU.	0.00% 0/163 • A treatment emergent AE during Ramadan (fasting) had onset on or after the individual subject's first day of Ramadan fasting, and no later than the individual subject's last day of Ramadan fasting. Safety analysis set included all randomised subjects who were exposed to the trial drug. Subjects in the safety analysis set contributed to the evaluation 'as treated'. A total of 315 randomised subjects were exposed to trial products during Ramadan (fasting), of which 152 subjects were exposed to liraglutide and 163 subjects were exposed to SU.

Other adverse events

Measure	Liraglutide and Metformin n=152 participants at risk Liraglutide 1.8 mg administered once daily subcutaneously, in combination with pre-trial tablet metformin of unchanged dose.	Sulfonylurea and Metformin n=163 participants at risk Subjects continued on pre-trial sulfonylurea tablet treatment, in combination with pre-trial tablet metformin of unchanged dose.
Gastrointestinal disorders Vomiting	5.3% 8/152 • Number of events 9 • A treatment emergent AE during Ramadan (fasting) had onset on or after the individual subject's first day of Ramadan fasting, and no later than the individual subject's last day of Ramadan fasting. Safety analysis set included all randomised subjects who were exposed to the trial drug. Subjects in the safety analysis set contributed to the evaluation 'as treated'. A total of 315 randomised subjects were exposed to trial products during Ramadan (fasting), of which 152 subjects were exposed to liraglutide and 163 subjects were exposed to SU.	0.61% 1/163 • Number of events 1 • A treatment emergent AE during Ramadan (fasting) had onset on or after the individual subject's first day of Ramadan fasting, and no later than the individual subject's last day of Ramadan fasting. Safety analysis set included all randomised subjects who were exposed to the trial drug. Subjects in the safety analysis set contributed to the evaluation 'as treated'. A total of 315 randomised subjects were exposed to trial products during Ramadan (fasting), of which 152 subjects were exposed to liraglutide and 163 subjects were exposed to SU.

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