Trial Outcomes & Findings for Efficacy and Safety of Liraglutide Versus Placebo as add-on to Existing Diabetes Medication in Subjects With Type 2 Diabetes and Moderate Renal Impairment (NCT NCT01620489)

NCT ID: NCT01620489

Last Updated: 2019-03-19

Results Overview

Calculated as the estimated mean change from baseline in HbA1c (%) after 26 Weeks of treatment based on the statistical model.

• Recruitment status: COMPLETED
• Study phase: PHASE3
• Target enrollment: 279 participants
• Primary outcome timeframe: Week 0, Week 26
• Results posted on: 2019-03-19

Participant Flow

This trial was conducted in France, Poland, Russian Federation, Ukraine, United Kingdom, and the United States of America.

Participant milestones

Measure	Lira 1.8 mg Subjects received subcutaneous (s.c) liraglutide 1.8 mg once daily, applying a 3-4 week dose escalation regimen with weekly increments of 0.6 mg until the maintenance dose of 1.8 mg was reached, as an add-on to the subject's stable pre-trial oral antidiabetic drug (OAD) and/or insulin regimen (monotherapy or any duo-combinations of metformin and/or sulphonylureas and/or pioglitazone; or monotherapy of basal or premix insulin or combination with metformin and/or pioglitazone).	Placebo Subjects received s.c placebo 1.8 mg once daily, applying a 3-4 week dose escalation regimen with weekly increments of 0.6 mg until the maintenance dose of 1.8 mg was reached, as an add-on to the subject's stable pre-trial OAD and/or insulin regimen (monotherapy or any duo-combinations of metformin and/or sulphonylureas and/or pioglitazone; or monotherapy of basal or premix insulin or combination with metformin and/or pioglitazone).
Overall Study STARTED	140	139
Overall Study Exposed	140	137
Overall Study COMPLETED	105	105
Overall Study NOT COMPLETED	35	34

Reasons for withdrawal

Measure	Lira 1.8 mg Subjects received subcutaneous (s.c) liraglutide 1.8 mg once daily, applying a 3-4 week dose escalation regimen with weekly increments of 0.6 mg until the maintenance dose of 1.8 mg was reached, as an add-on to the subject's stable pre-trial oral antidiabetic drug (OAD) and/or insulin regimen (monotherapy or any duo-combinations of metformin and/or sulphonylureas and/or pioglitazone; or monotherapy of basal or premix insulin or combination with metformin and/or pioglitazone).	Placebo Subjects received s.c placebo 1.8 mg once daily, applying a 3-4 week dose escalation regimen with weekly increments of 0.6 mg until the maintenance dose of 1.8 mg was reached, as an add-on to the subject's stable pre-trial OAD and/or insulin regimen (monotherapy or any duo-combinations of metformin and/or sulphonylureas and/or pioglitazone; or monotherapy of basal or premix insulin or combination with metformin and/or pioglitazone).
Overall Study Adverse Event	17	4
Overall Study Protocol Violation	0	3
Overall Study Withdrawal Criteria	17	25
Overall Study Unclassified	1	2

Baseline Characteristics

Efficacy and Safety of Liraglutide Versus Placebo as add-on to Existing Diabetes Medication in Subjects With Type 2 Diabetes and Moderate Renal Impairment

Baseline characteristics by cohort

Measure	Lira 1.8 mg n=140 Participants Subjects received subcutaneous (s.c) liraglutide 1.8 mg once daily, applying a 3-4 week dose escalation regimen with weekly increments of 0.6 mg until the maintenance dose of 1.8 mg was reached, as an add-on to the subject's stable pre-trial oral antidiabetic drug (OAD) and/or insulin regimen (monotherapy or any duo-combinations of metformin and/or sulphonylureas and/or pioglitazone; or monotherapy of basal or premix insulin or combination with metformin and/or pioglitazone).	Placebo n=137 Participants Subjects received s.c placebo 1.8 mg once daily, applying a 3-4 week dose escalation regimen with weekly increments of 0.6 mg until the maintenance dose of 1.8 mg was reached, as an add-on to the subject's stable pre-trial OAD and/or insulin regimen (monotherapy or any duo-combinations of metformin and/or sulphonylureas and/or pioglitazone; or monotherapy of basal or premix insulin or combination with metformin and/or pioglitazone).	Total n=277 Participants Total of all reporting groups
Age, Continuous	68.0 years STANDARD_DEVIATION 8.3 • n=5 Participants	66.3 years STANDARD_DEVIATION 8.0 • n=7 Participants	67.2 years STANDARD_DEVIATION 8.2 • n=5 Participants
Sex: Female, Male Female	65 Participants n=5 Participants	72 Participants n=7 Participants	137 Participants n=5 Participants
Sex: Female, Male Male	75 Participants n=5 Participants	65 Participants n=7 Participants	140 Participants n=5 Participants
Fasting plasma glucose (FPG)	9.48 mmol/L STANDARD_DEVIATION 3.270 • n=5 Participants	9.27 mmol/L STANDARD_DEVIATION 2.842 • n=7 Participants	9.38 mmol/L STANDARD_DEVIATION 3.061 • n=5 Participants
Glycosylated haemoglobin (%)(HbA1c)	8.08 Percent (%) glycosylated haemoglobin STANDARD_DEVIATION 0.792 • n=5 Participants	8.00 Percent (%) glycosylated haemoglobin STANDARD_DEVIATION 0.853 • n=7 Participants	8.04 Percent (%) glycosylated haemoglobin STANDARD_DEVIATION 0.823 • n=5 Participants

PRIMARY outcome

Timeframe: Week 0, Week 26

Population: The full analysis set (FAS) included all randomised subjects that received at least one dose of the study medication. A total of 14 subjects in the FAS did not contribute to the analysis due to missing data.

Calculated as the estimated mean change from baseline in HbA1c (%) after 26 Weeks of treatment based on the statistical model.

Outcome measures

Measure	Lira 1.8 mg n=127 Participants Subjects received subcutaneous (s.c) liraglutide 1.8 mg once daily, applying a 3-4 week dose escalation regimen with weekly increments of 0.6 mg until the maintenance dose of 1.8 mg was reached, as an add-on to the subject's stable pre-trial oral antidiabetic drug (OAD) and/or insulin regimen (monotherapy or any duo-combinations of metformin and/or sulphonylureas and/or pioglitazone; or monotherapy of basal or premix insulin or combination with metformin and/or pioglitazone).	Placebo n=136 Participants Subjects received s.c placebo 1.8 mg once daily, applying a 3-4 week dose escalation regimen with weekly increments of 0.6 mg until the maintenance dose of 1.8 mg was reached, as an add-on to the subject's stable pre-trial OAD and/or insulin regimen (monotherapy or any duo-combinations of metformin and/or sulphonylureas and/or pioglitazone; or monotherapy of basal or premix insulin or combination with metformin and/or pioglitazone).
Estimated Mean From the Statistical Model and Standard Deviation From Observed Data For Change From Baseline to Week 26 in HbA1c (%) (Glycosylated Haemoglobin)	-1.05 percentage (%) Standard Deviation 0.8944	-0.38 percentage (%) Standard Deviation 0.8797

SECONDARY outcome

Timeframe: At week 26

Population: The FAS included all randomised subjects that received at least one dose of study medication. A total of 14 subjects in the FAS did not contribute to the analysis due to missing data.

Calculated as estimated percentage of subjects achieving HbA1c <7.0% and no weight gain after 26 weeks of treatment based on the statistical model.

Outcome measures

Measure	Lira 1.8 mg n=127 Participants Subjects received subcutaneous (s.c) liraglutide 1.8 mg once daily, applying a 3-4 week dose escalation regimen with weekly increments of 0.6 mg until the maintenance dose of 1.8 mg was reached, as an add-on to the subject's stable pre-trial oral antidiabetic drug (OAD) and/or insulin regimen (monotherapy or any duo-combinations of metformin and/or sulphonylureas and/or pioglitazone; or monotherapy of basal or premix insulin or combination with metformin and/or pioglitazone).	Placebo n=136 Participants Subjects received s.c placebo 1.8 mg once daily, applying a 3-4 week dose escalation regimen with weekly increments of 0.6 mg until the maintenance dose of 1.8 mg was reached, as an add-on to the subject's stable pre-trial OAD and/or insulin regimen (monotherapy or any duo-combinations of metformin and/or sulphonylureas and/or pioglitazone; or monotherapy of basal or premix insulin or combination with metformin and/or pioglitazone).
Estimated Proportion of Responders Achieving HbA1c <7.0% and no Weight Gain After 26 Weeks of Treatment	46.03 percentage of patients	15.99 percentage of patients

SECONDARY outcome

Timeframe: At week 26

Population: The FAS included all randomised subjects that received at least one dose of study medication. A total of 14 subjects in the FAS did not contribute to the analysis due to missing data.

Calculated as estimated percentage of subjects achieving HbA1c <7.0% and no minor or severe hypoglycaemic episodes observed within 26 weeks of treatment based on the statistical model.

Outcome measures

Measure	Lira 1.8 mg n=127 Participants Subjects received subcutaneous (s.c) liraglutide 1.8 mg once daily, applying a 3-4 week dose escalation regimen with weekly increments of 0.6 mg until the maintenance dose of 1.8 mg was reached, as an add-on to the subject's stable pre-trial oral antidiabetic drug (OAD) and/or insulin regimen (monotherapy or any duo-combinations of metformin and/or sulphonylureas and/or pioglitazone; or monotherapy of basal or premix insulin or combination with metformin and/or pioglitazone).	Placebo n=136 Participants Subjects received s.c placebo 1.8 mg once daily, applying a 3-4 week dose escalation regimen with weekly increments of 0.6 mg until the maintenance dose of 1.8 mg was reached, as an add-on to the subject's stable pre-trial OAD and/or insulin regimen (monotherapy or any duo-combinations of metformin and/or sulphonylureas and/or pioglitazone; or monotherapy of basal or premix insulin or combination with metformin and/or pioglitazone).
Estimated Proportion of Responders Achieving HbA1c <7.0% and no Minor or Severe Hypoglycaemic Episodes After 26 Weeks of Treatment	33.23 percentage of patients	11.23 percentage of patients

SECONDARY outcome

Timeframe: Week 0, week 26

Population: The FAS included all randomised subjects that received at least one dose of study medication. A total of 46 subjects in the FAS did not contribute to the analysis due to missing data.

SMPG was measured before and 90 minutes after breakfast, lunch and dinner and at bedtime at Week 0, 12 and 26. A summary measure of the 7 values was derived for each applicable visit as the area under the curve divided by the period of time elapsed between the first and last measurement. The change from baseline to week 26 was estimated using the statistical model.

Outcome measures

Measure	Lira 1.8 mg n=109 Participants Subjects received subcutaneous (s.c) liraglutide 1.8 mg once daily, applying a 3-4 week dose escalation regimen with weekly increments of 0.6 mg until the maintenance dose of 1.8 mg was reached, as an add-on to the subject's stable pre-trial oral antidiabetic drug (OAD) and/or insulin regimen (monotherapy or any duo-combinations of metformin and/or sulphonylureas and/or pioglitazone; or monotherapy of basal or premix insulin or combination with metformin and/or pioglitazone).	Placebo n=122 Participants Subjects received s.c placebo 1.8 mg once daily, applying a 3-4 week dose escalation regimen with weekly increments of 0.6 mg until the maintenance dose of 1.8 mg was reached, as an add-on to the subject's stable pre-trial OAD and/or insulin regimen (monotherapy or any duo-combinations of metformin and/or sulphonylureas and/or pioglitazone; or monotherapy of basal or premix insulin or combination with metformin and/or pioglitazone).
Estimated Mean From the Statistical Model and Standard Deviation From Observed Data For Change From Baseline to Week 26 in Self-measured Plasma Glucose (SMPG) 7-point Profiles	-1.59 mmol/L Standard Deviation 2.480	-0.51 mmol/L Standard Deviation 2.391

SECONDARY outcome

Timeframe: Week 0, week 26

Population: The FAS included all randomised subjects that received at least one dose of study medication. A total of 14 subjects in the FAS did not contribute to the analysis due to missing data.

Calculated as estimated mean change in BMI (kg/m˄2) from baseline to Week 26 based on the statistical model.

Outcome measures

Measure	Lira 1.8 mg n=127 Participants Subjects received subcutaneous (s.c) liraglutide 1.8 mg once daily, applying a 3-4 week dose escalation regimen with weekly increments of 0.6 mg until the maintenance dose of 1.8 mg was reached, as an add-on to the subject's stable pre-trial oral antidiabetic drug (OAD) and/or insulin regimen (monotherapy or any duo-combinations of metformin and/or sulphonylureas and/or pioglitazone; or monotherapy of basal or premix insulin or combination with metformin and/or pioglitazone).	Placebo n=136 Participants Subjects received s.c placebo 1.8 mg once daily, applying a 3-4 week dose escalation regimen with weekly increments of 0.6 mg until the maintenance dose of 1.8 mg was reached, as an add-on to the subject's stable pre-trial OAD and/or insulin regimen (monotherapy or any duo-combinations of metformin and/or sulphonylureas and/or pioglitazone; or monotherapy of basal or premix insulin or combination with metformin and/or pioglitazone).
Estimated Mean From the Statistical Model and Standard Deviation From Observed Data For Change From Baseline to Week 26 in Body Mass Index (BMI)	-0.88 kg/m^2 Standard Deviation 1.3214	-0.38 kg/m^2 Standard Deviation 1.1679

SECONDARY outcome

Timeframe: Week 0, week 26

Population: Safety analysis set included all subjects receiving at least one dose of the trial product. A total of 8 subjects in the safety analysis set did not contribute to the analysis due to missing data.

Calculated as the estimated ratio to baseline in eGFR (mL/min/1.73m˄2) after 26 Weeks of treatment based on the statistical model.

Outcome measures

Measure	Lira 1.8 mg n=132 Participants Subjects received subcutaneous (s.c) liraglutide 1.8 mg once daily, applying a 3-4 week dose escalation regimen with weekly increments of 0.6 mg until the maintenance dose of 1.8 mg was reached, as an add-on to the subject's stable pre-trial oral antidiabetic drug (OAD) and/or insulin regimen (monotherapy or any duo-combinations of metformin and/or sulphonylureas and/or pioglitazone; or monotherapy of basal or premix insulin or combination with metformin and/or pioglitazone).	Placebo n=137 Participants Subjects received s.c placebo 1.8 mg once daily, applying a 3-4 week dose escalation regimen with weekly increments of 0.6 mg until the maintenance dose of 1.8 mg was reached, as an add-on to the subject's stable pre-trial OAD and/or insulin regimen (monotherapy or any duo-combinations of metformin and/or sulphonylureas and/or pioglitazone; or monotherapy of basal or premix insulin or combination with metformin and/or pioglitazone).
Estimated Mean Ratio to Baseline and Observed Coefficient of Variation in Renal Function-estimated Glomerular Filtration Rate (eGFR) (to Check How Well the Kidneys Are Functioning Using Modification of Diet in Renal Disease (MDRD) Formula)	0.99 mL/min/1.73m˄2 Geometric Coefficient of Variation 0.17	1.01 mL/min/1.73m˄2 Geometric Coefficient of Variation 0.19

Adverse Events

Lira 1.8 mg

Serious events: 14 serious events

Other events: 73 other events

Deaths: 0 deaths

Placebo

Serious events: 15 serious events

Other events: 49 other events

Deaths: 0 deaths

Serious adverse events

Measure	Lira 1.8 mg n=140 participants at risk Subjects received subcutaneous (s.c) liraglutide 1.8 mg once daily, applying a 3-4 week dose escalation regimen with weekly increments of 0.6 mg until the maintenance dose of 1.8 mg was reached, as an add-on to the subject's stable pre-trial oral antidiabetic drug (OAD) and/or insulin regimen (monotherapy or any duo-combinations of metformin and/or sulphonylureas and/or pioglitazone; or monotherapy of basal or premix insulin or combination with metformin and/or pioglitazone).	Placebo n=137 participants at risk Subjects received s.c placebo 1.8 mg once daily, applying a 3-4 week dose escalation regimen with weekly increments of 0.6 mg until the maintenance dose of 1.8 mg was reached, as an add-on to the subject's stable pre-trial OAD and/or insulin regimen (monotherapy or any duo-combinations of metformin and/or sulphonylureas and/or pioglitazone; or monotherapy of basal or premix insulin or combination with metformin and/or pioglitazone).
Blood and lymphatic system disorders Anaemia	0.00% 0/140 • The adverse events were collected from Week 0 to Week 27±3 Days Safety analysis set included all subjects receiving at least one dose of the investigational product.	0.73% 1/137 • Number of events 1 • The adverse events were collected from Week 0 to Week 27±3 Days Safety analysis set included all subjects receiving at least one dose of the investigational product.
Cardiac disorders Acute myocardial infarction	0.71% 1/140 • Number of events 1 • The adverse events were collected from Week 0 to Week 27±3 Days Safety analysis set included all subjects receiving at least one dose of the investigational product.	0.73% 1/137 • Number of events 1 • The adverse events were collected from Week 0 to Week 27±3 Days Safety analysis set included all subjects receiving at least one dose of the investigational product.
Cardiac disorders Cardiac failure congestive	0.71% 1/140 • Number of events 1 • The adverse events were collected from Week 0 to Week 27±3 Days Safety analysis set included all subjects receiving at least one dose of the investigational product.	0.00% 0/137 • The adverse events were collected from Week 0 to Week 27±3 Days Safety analysis set included all subjects receiving at least one dose of the investigational product.
Cardiac disorders Left ventricular failure	0.71% 1/140 • Number of events 1 • The adverse events were collected from Week 0 to Week 27±3 Days Safety analysis set included all subjects receiving at least one dose of the investigational product.	0.00% 0/137 • The adverse events were collected from Week 0 to Week 27±3 Days Safety analysis set included all subjects receiving at least one dose of the investigational product.
Cardiac disorders Myocardial infarction	0.71% 1/140 • Number of events 1 • The adverse events were collected from Week 0 to Week 27±3 Days Safety analysis set included all subjects receiving at least one dose of the investigational product.	0.00% 0/137 • The adverse events were collected from Week 0 to Week 27±3 Days Safety analysis set included all subjects receiving at least one dose of the investigational product.
Gastrointestinal disorders Abdominal pain lower	0.00% 0/140 • The adverse events were collected from Week 0 to Week 27±3 Days Safety analysis set included all subjects receiving at least one dose of the investigational product.	0.73% 1/137 • Number of events 1 • The adverse events were collected from Week 0 to Week 27±3 Days Safety analysis set included all subjects receiving at least one dose of the investigational product.
Gastrointestinal disorders Gastric ulcer haemorrhage	0.00% 0/140 • The adverse events were collected from Week 0 to Week 27±3 Days Safety analysis set included all subjects receiving at least one dose of the investigational product.	0.73% 1/137 • Number of events 1 • The adverse events were collected from Week 0 to Week 27±3 Days Safety analysis set included all subjects receiving at least one dose of the investigational product.
Gastrointestinal disorders Gastrointestinal haemorrhage	0.00% 0/140 • The adverse events were collected from Week 0 to Week 27±3 Days Safety analysis set included all subjects receiving at least one dose of the investigational product.	0.73% 1/137 • Number of events 1 • The adverse events were collected from Week 0 to Week 27±3 Days Safety analysis set included all subjects receiving at least one dose of the investigational product.
General disorders Chest pain	0.71% 1/140 • Number of events 1 • The adverse events were collected from Week 0 to Week 27±3 Days Safety analysis set included all subjects receiving at least one dose of the investigational product.	0.00% 0/137 • The adverse events were collected from Week 0 to Week 27±3 Days Safety analysis set included all subjects receiving at least one dose of the investigational product.
Hepatobiliary disorders Autoimmune hepatitis	0.00% 0/140 • The adverse events were collected from Week 0 to Week 27±3 Days Safety analysis set included all subjects receiving at least one dose of the investigational product.	0.73% 1/137 • Number of events 1 • The adverse events were collected from Week 0 to Week 27±3 Days Safety analysis set included all subjects receiving at least one dose of the investigational product.
Hepatobiliary disorders Cholecystitis	0.71% 1/140 • Number of events 1 • The adverse events were collected from Week 0 to Week 27±3 Days Safety analysis set included all subjects receiving at least one dose of the investigational product.	0.00% 0/137 • The adverse events were collected from Week 0 to Week 27±3 Days Safety analysis set included all subjects receiving at least one dose of the investigational product.
Infections and infestations Arteriosclerotic gangrene	0.00% 0/140 • The adverse events were collected from Week 0 to Week 27±3 Days Safety analysis set included all subjects receiving at least one dose of the investigational product.	0.73% 1/137 • Number of events 1 • The adverse events were collected from Week 0 to Week 27±3 Days Safety analysis set included all subjects receiving at least one dose of the investigational product.
Infections and infestations Biliary sepsis	0.71% 1/140 • Number of events 1 • The adverse events were collected from Week 0 to Week 27±3 Days Safety analysis set included all subjects receiving at least one dose of the investigational product.	0.00% 0/137 • The adverse events were collected from Week 0 to Week 27±3 Days Safety analysis set included all subjects receiving at least one dose of the investigational product.
Infections and infestations Meningitis herpes	0.71% 1/140 • Number of events 1 • The adverse events were collected from Week 0 to Week 27±3 Days Safety analysis set included all subjects receiving at least one dose of the investigational product.	0.00% 0/137 • The adverse events were collected from Week 0 to Week 27±3 Days Safety analysis set included all subjects receiving at least one dose of the investigational product.
Infections and infestations Osteomyelitis	0.00% 0/140 • The adverse events were collected from Week 0 to Week 27±3 Days Safety analysis set included all subjects receiving at least one dose of the investigational product.	0.73% 1/137 • Number of events 1 • The adverse events were collected from Week 0 to Week 27±3 Days Safety analysis set included all subjects receiving at least one dose of the investigational product.
Infections and infestations Pneumonia	0.71% 1/140 • Number of events 1 • The adverse events were collected from Week 0 to Week 27±3 Days Safety analysis set included all subjects receiving at least one dose of the investigational product.	0.00% 0/137 • The adverse events were collected from Week 0 to Week 27±3 Days Safety analysis set included all subjects receiving at least one dose of the investigational product.
Injury, poisoning and procedural complications Fall	0.00% 0/140 • The adverse events were collected from Week 0 to Week 27±3 Days Safety analysis set included all subjects receiving at least one dose of the investigational product.	0.73% 1/137 • Number of events 1 • The adverse events were collected from Week 0 to Week 27±3 Days Safety analysis set included all subjects receiving at least one dose of the investigational product.
Injury, poisoning and procedural complications Spinal cord injury lumbar	0.00% 0/140 • The adverse events were collected from Week 0 to Week 27±3 Days Safety analysis set included all subjects receiving at least one dose of the investigational product.	0.73% 1/137 • Number of events 1 • The adverse events were collected from Week 0 to Week 27±3 Days Safety analysis set included all subjects receiving at least one dose of the investigational product.
Investigations C-reactive protein increased	0.71% 1/140 • Number of events 1 • The adverse events were collected from Week 0 to Week 27±3 Days Safety analysis set included all subjects receiving at least one dose of the investigational product.	0.00% 0/137 • The adverse events were collected from Week 0 to Week 27±3 Days Safety analysis set included all subjects receiving at least one dose of the investigational product.
Investigations Glomerular filtration rate decreased	0.00% 0/140 • The adverse events were collected from Week 0 to Week 27±3 Days Safety analysis set included all subjects receiving at least one dose of the investigational product.	0.73% 1/137 • Number of events 1 • The adverse events were collected from Week 0 to Week 27±3 Days Safety analysis set included all subjects receiving at least one dose of the investigational product.
Investigations Urine albumin/creatinine ratio increased	0.71% 1/140 • Number of events 1 • The adverse events were collected from Week 0 to Week 27±3 Days Safety analysis set included all subjects receiving at least one dose of the investigational product.	0.00% 0/137 • The adverse events were collected from Week 0 to Week 27±3 Days Safety analysis set included all subjects receiving at least one dose of the investigational product.
Metabolism and nutrition disorders Diabetes mellitus	0.71% 1/140 • Number of events 1 • The adverse events were collected from Week 0 to Week 27±3 Days Safety analysis set included all subjects receiving at least one dose of the investigational product.	0.73% 1/137 • Number of events 1 • The adverse events were collected from Week 0 to Week 27±3 Days Safety analysis set included all subjects receiving at least one dose of the investigational product.
Metabolism and nutrition disorders Diabetic ketoacidosis	0.71% 1/140 • Number of events 1 • The adverse events were collected from Week 0 to Week 27±3 Days Safety analysis set included all subjects receiving at least one dose of the investigational product.	0.00% 0/137 • The adverse events were collected from Week 0 to Week 27±3 Days Safety analysis set included all subjects receiving at least one dose of the investigational product.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Adenocarcinoma of colon	0.00% 0/140 • The adverse events were collected from Week 0 to Week 27±3 Days Safety analysis set included all subjects receiving at least one dose of the investigational product.	0.73% 1/137 • Number of events 1 • The adverse events were collected from Week 0 to Week 27±3 Days Safety analysis set included all subjects receiving at least one dose of the investigational product.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Benign neoplasm of cervix uteri	0.00% 0/140 • The adverse events were collected from Week 0 to Week 27±3 Days Safety analysis set included all subjects receiving at least one dose of the investigational product.	0.73% 1/137 • Number of events 1 • The adverse events were collected from Week 0 to Week 27±3 Days Safety analysis set included all subjects receiving at least one dose of the investigational product.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Endometrial adenocarcinoma	0.00% 0/140 • The adverse events were collected from Week 0 to Week 27±3 Days Safety analysis set included all subjects receiving at least one dose of the investigational product.	0.73% 1/137 • Number of events 1 • The adverse events were collected from Week 0 to Week 27±3 Days Safety analysis set included all subjects receiving at least one dose of the investigational product.
Nervous system disorders Cerebral haemorrhage	0.71% 1/140 • Number of events 1 • The adverse events were collected from Week 0 to Week 27±3 Days Safety analysis set included all subjects receiving at least one dose of the investigational product.	0.00% 0/137 • The adverse events were collected from Week 0 to Week 27±3 Days Safety analysis set included all subjects receiving at least one dose of the investigational product.
Nervous system disorders Cerebrovascular accident	0.71% 1/140 • Number of events 1 • The adverse events were collected from Week 0 to Week 27±3 Days Safety analysis set included all subjects receiving at least one dose of the investigational product.	0.00% 0/137 • The adverse events were collected from Week 0 to Week 27±3 Days Safety analysis set included all subjects receiving at least one dose of the investigational product.
Nervous system disorders Syncope	1.4% 2/140 • Number of events 2 • The adverse events were collected from Week 0 to Week 27±3 Days Safety analysis set included all subjects receiving at least one dose of the investigational product.	0.00% 0/137 • The adverse events were collected from Week 0 to Week 27±3 Days Safety analysis set included all subjects receiving at least one dose of the investigational product.
Renal and urinary disorders Renal impairment	0.71% 1/140 • Number of events 1 • The adverse events were collected from Week 0 to Week 27±3 Days Safety analysis set included all subjects receiving at least one dose of the investigational product.	0.73% 1/137 • Number of events 1 • The adverse events were collected from Week 0 to Week 27±3 Days Safety analysis set included all subjects receiving at least one dose of the investigational product.
Renal and urinary disorders Urethral stenosis	0.00% 0/140 • The adverse events were collected from Week 0 to Week 27±3 Days Safety analysis set included all subjects receiving at least one dose of the investigational product.	0.73% 1/137 • Number of events 1 • The adverse events were collected from Week 0 to Week 27±3 Days Safety analysis set included all subjects receiving at least one dose of the investigational product.
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	0.71% 1/140 • Number of events 1 • The adverse events were collected from Week 0 to Week 27±3 Days Safety analysis set included all subjects receiving at least one dose of the investigational product.	0.00% 0/137 • The adverse events were collected from Week 0 to Week 27±3 Days Safety analysis set included all subjects receiving at least one dose of the investigational product.
Respiratory, thoracic and mediastinal disorders Pulmonary fibrosis	0.71% 1/140 • Number of events 1 • The adverse events were collected from Week 0 to Week 27±3 Days Safety analysis set included all subjects receiving at least one dose of the investigational product.	0.00% 0/137 • The adverse events were collected from Week 0 to Week 27±3 Days Safety analysis set included all subjects receiving at least one dose of the investigational product.
Respiratory, thoracic and mediastinal disorders Pulmonary oedema	0.71% 1/140 • Number of events 1 • The adverse events were collected from Week 0 to Week 27±3 Days Safety analysis set included all subjects receiving at least one dose of the investigational product.	0.00% 0/137 • The adverse events were collected from Week 0 to Week 27±3 Days Safety analysis set included all subjects receiving at least one dose of the investigational product.
Surgical and medical procedures Colectomy	0.00% 0/140 • The adverse events were collected from Week 0 to Week 27±3 Days Safety analysis set included all subjects receiving at least one dose of the investigational product.	0.73% 1/137 • Number of events 1 • The adverse events were collected from Week 0 to Week 27±3 Days Safety analysis set included all subjects receiving at least one dose of the investigational product.
Vascular disorders Arteriosclerosis	0.00% 0/140 • The adverse events were collected from Week 0 to Week 27±3 Days Safety analysis set included all subjects receiving at least one dose of the investigational product.	0.73% 1/137 • Number of events 1 • The adverse events were collected from Week 0 to Week 27±3 Days Safety analysis set included all subjects receiving at least one dose of the investigational product.
Vascular disorders Poor peripheral circulation	0.00% 0/140 • The adverse events were collected from Week 0 to Week 27±3 Days Safety analysis set included all subjects receiving at least one dose of the investigational product.	0.73% 1/137 • Number of events 1 • The adverse events were collected from Week 0 to Week 27±3 Days Safety analysis set included all subjects receiving at least one dose of the investigational product.

Other adverse events

Measure	Lira 1.8 mg n=140 participants at risk Subjects received subcutaneous (s.c) liraglutide 1.8 mg once daily, applying a 3-4 week dose escalation regimen with weekly increments of 0.6 mg until the maintenance dose of 1.8 mg was reached, as an add-on to the subject's stable pre-trial oral antidiabetic drug (OAD) and/or insulin regimen (monotherapy or any duo-combinations of metformin and/or sulphonylureas and/or pioglitazone; or monotherapy of basal or premix insulin or combination with metformin and/or pioglitazone).	Placebo n=137 participants at risk Subjects received s.c placebo 1.8 mg once daily, applying a 3-4 week dose escalation regimen with weekly increments of 0.6 mg until the maintenance dose of 1.8 mg was reached, as an add-on to the subject's stable pre-trial OAD and/or insulin regimen (monotherapy or any duo-combinations of metformin and/or sulphonylureas and/or pioglitazone; or monotherapy of basal or premix insulin or combination with metformin and/or pioglitazone).
Gastrointestinal disorders Constipation	5.7% 8/140 • Number of events 9 • The adverse events were collected from Week 0 to Week 27±3 Days Safety analysis set included all subjects receiving at least one dose of the investigational product.	1.5% 2/137 • Number of events 2 • The adverse events were collected from Week 0 to Week 27±3 Days Safety analysis set included all subjects receiving at least one dose of the investigational product.
Gastrointestinal disorders Diarrhoea	7.1% 10/140 • Number of events 13 • The adverse events were collected from Week 0 to Week 27±3 Days Safety analysis set included all subjects receiving at least one dose of the investigational product.	2.9% 4/137 • Number of events 6 • The adverse events were collected from Week 0 to Week 27±3 Days Safety analysis set included all subjects receiving at least one dose of the investigational product.
Gastrointestinal disorders Nausea	21.4% 30/140 • Number of events 39 • The adverse events were collected from Week 0 to Week 27±3 Days Safety analysis set included all subjects receiving at least one dose of the investigational product.	4.4% 6/137 • Number of events 10 • The adverse events were collected from Week 0 to Week 27±3 Days Safety analysis set included all subjects receiving at least one dose of the investigational product.
Gastrointestinal disorders Vomiting	12.1% 17/140 • Number of events 18 • The adverse events were collected from Week 0 to Week 27±3 Days Safety analysis set included all subjects receiving at least one dose of the investigational product.	2.2% 3/137 • Number of events 4 • The adverse events were collected from Week 0 to Week 27±3 Days Safety analysis set included all subjects receiving at least one dose of the investigational product.
Infections and infestations Nasopharyngitis	5.0% 7/140 • Number of events 7 • The adverse events were collected from Week 0 to Week 27±3 Days Safety analysis set included all subjects receiving at least one dose of the investigational product.	11.7% 16/137 • Number of events 17 • The adverse events were collected from Week 0 to Week 27±3 Days Safety analysis set included all subjects receiving at least one dose of the investigational product.
Infections and infestations Upper respiratory tract infection	2.9% 4/140 • Number of events 4 • The adverse events were collected from Week 0 to Week 27±3 Days Safety analysis set included all subjects receiving at least one dose of the investigational product.	5.1% 7/137 • Number of events 8 • The adverse events were collected from Week 0 to Week 27±3 Days Safety analysis set included all subjects receiving at least one dose of the investigational product.
Investigations Glomerular filtration rate decreased	6.4% 9/140 • Number of events 10 • The adverse events were collected from Week 0 to Week 27±3 Days Safety analysis set included all subjects receiving at least one dose of the investigational product.	5.1% 7/137 • Number of events 14 • The adverse events were collected from Week 0 to Week 27±3 Days Safety analysis set included all subjects receiving at least one dose of the investigational product.
Investigations Lipase increased	15.0% 21/140 • Number of events 23 • The adverse events were collected from Week 0 to Week 27±3 Days Safety analysis set included all subjects receiving at least one dose of the investigational product.	8.8% 12/137 • Number of events 13 • The adverse events were collected from Week 0 to Week 27±3 Days Safety analysis set included all subjects receiving at least one dose of the investigational product.
Nervous system disorders Headache	5.0% 7/140 • Number of events 8 • The adverse events were collected from Week 0 to Week 27±3 Days Safety analysis set included all subjects receiving at least one dose of the investigational product.	2.9% 4/137 • Number of events 8 • The adverse events were collected from Week 0 to Week 27±3 Days Safety analysis set included all subjects receiving at least one dose of the investigational product.
Renal and urinary disorders Renal impairment	5.0% 7/140 • Number of events 7 • The adverse events were collected from Week 0 to Week 27±3 Days Safety analysis set included all subjects receiving at least one dose of the investigational product.	5.8% 8/137 • Number of events 8 • The adverse events were collected from Week 0 to Week 27±3 Days Safety analysis set included all subjects receiving at least one dose of the investigational product.

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