Trial Outcomes & Findings for Efficacy in Controlling Glycaemia With Victoza® (Liraglutide) as add-on to Metformin vs. OADs as add-on to Metformin After up to 104 Weeks of Treatment in Subjects With Type 2 Diabetes (NCT NCT02730377)

Last Updated: 2020-07-07

Results Overview

Inadequate glycaemic control was defined as glycosylated haemoglobin (HbA1c) of 7.0% (53 mmol/mol) or greater at two consecutive visits after the first 26 weeks of treatment and up to 104 weeks. 25%, median (50%) and 75% percentiles for the cumulative distribution function, are obtained from the Kaplan-Meier survival function. HbA1c was recorded at weeks 38, 52, 65, 78, 91 and 104.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

1991 participants

Primary outcome timeframe

Weeks 26-104

Results posted on

2020-07-07

Participant Flow

The trial was conducted at 219 sites in Canada (11), Colombia (3), India (16), Latvia (2), Lebanon (4), Russian Federation (5), Serbia (6), Turkey (4) and the United States (168).

Participants were randomised in a 1:1 manner to receive either liraglutide or an oral antidiabetic drug (OAD) both as add-on to background therapy with metformin.

Participant milestones

Participant milestones
Measure	Liraglutide 1.8 mg Participants were to receive a subcutaneous injection of liraglutide once daily. Participants received 0.6 milligrams (mg) liraglutide during the first week. The dose was escalated in weekly increments of 0.6 mg until the dose of 1.8 mg was reached. The treatment period was 104 weeks.	Oral Antidiabetic Drug Participants were to receive one selected OAD. The following OADs were allowed: alpha-glucosidase inhibitors, dipeptidyl peptidase-4 (DPP-4) inhibitors, meglitinides, sodium-glucose co-transporter-2 (SGLT-2) inhibitors, sulfonylureas or thiazolidinediones. The treatment period was 104 weeks.
Overall Study STARTED	996	995
Overall Study Treated	980	984
Overall Study Full Analysis Set (FAS)	996	995
Overall Study Safety Analysis Set (SAS)	980	984
Overall Study COMPLETED	446	362
Overall Study NOT COMPLETED	550	633

Reasons for withdrawal

Reasons for withdrawal
Measure	Liraglutide 1.8 mg Participants were to receive a subcutaneous injection of liraglutide once daily. Participants received 0.6 milligrams (mg) liraglutide during the first week. The dose was escalated in weekly increments of 0.6 mg until the dose of 1.8 mg was reached. The treatment period was 104 weeks.	Oral Antidiabetic Drug Participants were to receive one selected OAD. The following OADs were allowed: alpha-glucosidase inhibitors, dipeptidyl peptidase-4 (DPP-4) inhibitors, meglitinides, sodium-glucose co-transporter-2 (SGLT-2) inhibitors, sulfonylureas or thiazolidinediones. The treatment period was 104 weeks.
Overall Study Other	5	4
Overall Study Death	1	8
Overall Study Inadequate glycaemic control	368	473
Overall Study Adverse Event	79	41
Overall Study Protocol Violation	23	30
Overall Study Lack of Efficacy	4	13
Overall Study Pregnancy	0	1
Overall Study Withdrawal by Subject	45	42
Overall Study Lost to Follow-up	25	21

Baseline Characteristics

Efficacy in Controlling Glycaemia With Victoza® (Liraglutide) as add-on to Metformin vs. OADs as add-on to Metformin After up to 104 Weeks of Treatment in Subjects With Type 2 Diabetes

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Liraglutide 1.8 mg n=996 Participants Participants were to receive a subcutaneous injection of liraglutide once daily. Participants received 0.6 milligrams (mg) liraglutide during the first week. The dose was escalated in weekly increments of 0.6 mg until the dose of 1.8 mg was reached. The treatment period was 104 weeks.	Oral Antidiabetic Drug n=995 Participants Participants were to receive one selected OAD. The following OADs were allowed: alpha-glucosidase inhibitors, dipeptidyl peptidase-4 (DPP-4) inhibitors, meglitinides, sodium-glucose co-transporter-2 (SGLT-2) inhibitors, sulfonylureas or thiazolidinediones. The treatment period was 104 weeks.	Total n=1991 Participants Total of all reporting groups
Age, Continuous	57.6 Years STANDARD_DEVIATION 11.0 • n=5 Participants	57.1 Years STANDARD_DEVIATION 10.7 • n=7 Participants	57.4 Years STANDARD_DEVIATION 10.8 • n=5 Participants
Sex: Female, Male Female	476 Participants n=5 Participants	471 Participants n=7 Participants	947 Participants n=5 Participants
Sex: Female, Male Male	520 Participants n=5 Participants	524 Participants n=7 Participants	1044 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	176 Participants n=5 Participants	189 Participants n=7 Participants	365 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	820 Participants n=5 Participants	806 Participants n=7 Participants	1626 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	3 Participants n=5 Participants	6 Participants n=7 Participants	9 Participants n=5 Participants
Race/Ethnicity, Customized Asian	149 Participants n=5 Participants	141 Participants n=7 Participants	290 Participants n=5 Participants
Race/Ethnicity, Customized Black or African American	101 Participants n=5 Participants	106 Participants n=7 Participants	207 Participants n=5 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	3 Participants n=5 Participants	2 Participants n=7 Participants	5 Participants n=5 Participants
Race/Ethnicity, Customized White	724 Participants n=5 Participants	714 Participants n=7 Participants	1438 Participants n=5 Participants
Race/Ethnicity, Customized Other	16 Participants n=5 Participants	26 Participants n=7 Participants	42 Participants n=5 Participants

PRIMARY outcome

Timeframe: Weeks 26-104

Population: FAS included all randomised participants. Overall number of participants analyzed=participants with available data.

Outcome measures

Outcome measures
Measure	Liraglutide 1.8 mg n=416 Participants Participants were to receive a subcutaneous injection of liraglutide once daily. Participants received 0.6 milligrams (mg) liraglutide during the first week. The dose was escalated in weekly increments of 0.6 mg until the dose of 1.8 mg was reached. The treatment period was 104 weeks.	Oral Antidiabetic Drug n=547 Participants Participants were to receive one selected OAD. The following OADs were allowed: alpha-glucosidase inhibitors, dipeptidyl peptidase-4 (DPP-4) inhibitors, meglitinides, sodium-glucose co-transporter-2 (SGLT-2) inhibitors, sulfonylureas or thiazolidinediones. The treatment period was 104 weeks.
Time to Inadequate Glycaemic Control	108.9 Weeks Interval 37.7 to The 75 percentile data was not available as the proportion was not reached within study period.	64.9 Weeks Interval 35.4 to 107.4

SECONDARY outcome

Timeframe: Weeks 0-104

Population: FAS included all randomised participants. Overall number of participants analyzed=participants with available data.

The time to premature treatment discontinuation (for any reason including inadequate glycaemic control) was analysed and presented using the generalised log rank test. 25%, median (50%) and 75% percentiles for the cumulative distribution function, are obtained from the Kaplan-Meier survival function.

Outcome measures

Outcome measures
Measure	Liraglutide 1.8 mg n=532 Participants Participants were to receive a subcutaneous injection of liraglutide once daily. Participants received 0.6 milligrams (mg) liraglutide during the first week. The dose was escalated in weekly increments of 0.6 mg until the dose of 1.8 mg was reached. The treatment period was 104 weeks.	Oral Antidiabetic Drug n=624 Participants Participants were to receive one selected OAD. The following OADs were allowed: alpha-glucosidase inhibitors, dipeptidyl peptidase-4 (DPP-4) inhibitors, meglitinides, sodium-glucose co-transporter-2 (SGLT-2) inhibitors, sulfonylureas or thiazolidinediones. The treatment period was 104 weeks.
Time to Premature Treatment Discontinuation (for Any Reason Including Inadequate Glycaemic Control)	80.4 Weeks Interval 35.7 to The 75 percentile data was not available as the proportion was not reached within study period.	52.3 Weeks Interval 35.1 to The 75 percentile data was not available as the proportion was not reached within study period.

SECONDARY outcome

Timeframe: Week 0, week 104/premature treatment discontinuation

Population: Overall number of participants analyzed=FAS included all randomised participants. Number analyzed=participants with available data.

Change from baseline (week 0) in HbA1c at week 104 or at premature treatment discontinuation is presented.

Outcome measures

Outcome measures
Measure	Liraglutide 1.8 mg n=996 Participants Participants were to receive a subcutaneous injection of liraglutide once daily. Participants received 0.6 milligrams (mg) liraglutide during the first week. The dose was escalated in weekly increments of 0.6 mg until the dose of 1.8 mg was reached. The treatment period was 104 weeks.	Oral Antidiabetic Drug n=995 Participants Participants were to receive one selected OAD. The following OADs were allowed: alpha-glucosidase inhibitors, dipeptidyl peptidase-4 (DPP-4) inhibitors, meglitinides, sodium-glucose co-transporter-2 (SGLT-2) inhibitors, sulfonylureas or thiazolidinediones. The treatment period was 104 weeks.
Change in HbA1c Change at week 104	-1.4 Percentage point of HbA1c Standard Deviation 1.06	-1.1 Percentage point of HbA1c Standard Deviation 1.04
Change in HbA1c Change at premature treatment discontinuation	-0.6 Percentage point of HbA1c Standard Deviation 1.03	-0.2 Percentage point of HbA1c Standard Deviation 1.56

SECONDARY outcome

Timeframe: Week 104/Premature treatment discontinuation

Population: FAS included all randomised participants.

Participants who achieved HbA1c ≤6.5% (yes/no) is presented.

Outcome measures

Outcome measures
Measure	Liraglutide 1.8 mg n=996 Participants Participants were to receive a subcutaneous injection of liraglutide once daily. Participants received 0.6 milligrams (mg) liraglutide during the first week. The dose was escalated in weekly increments of 0.6 mg until the dose of 1.8 mg was reached. The treatment period was 104 weeks.	Oral Antidiabetic Drug n=995 Participants Participants were to receive one selected OAD. The following OADs were allowed: alpha-glucosidase inhibitors, dipeptidyl peptidase-4 (DPP-4) inhibitors, meglitinides, sodium-glucose co-transporter-2 (SGLT-2) inhibitors, sulfonylureas or thiazolidinediones. The treatment period was 104 weeks.
Participants Who Achieve HbA1c ≤6.5% (Yes/No) Yes	255 Participants	162 Participants
Participants Who Achieve HbA1c ≤6.5% (Yes/No) No	741 Participants	833 Participants

SECONDARY outcome

Timeframe: Week 104/Premature treatment discontinuation

Population: FAS included all randomised participants.

Participants who achieved HbA1c ≤7.0% without weight gain (yes/no) is presented.

Outcome measures

Outcome measures
Measure	Liraglutide 1.8 mg n=996 Participants Participants were to receive a subcutaneous injection of liraglutide once daily. Participants received 0.6 milligrams (mg) liraglutide during the first week. The dose was escalated in weekly increments of 0.6 mg until the dose of 1.8 mg was reached. The treatment period was 104 weeks.	Oral Antidiabetic Drug n=995 Participants Participants were to receive one selected OAD. The following OADs were allowed: alpha-glucosidase inhibitors, dipeptidyl peptidase-4 (DPP-4) inhibitors, meglitinides, sodium-glucose co-transporter-2 (SGLT-2) inhibitors, sulfonylureas or thiazolidinediones. The treatment period was 104 weeks.
Participants Who Achieve HbA1c ≤7.0% Without Weight Gain Yes	329 Participants	234 Participants
Participants Who Achieve HbA1c ≤7.0% Without Weight Gain No	667 Participants	761 Participants

SECONDARY outcome

Timeframe: Week 104/Premature treatment discontinuation

Population: FAS included all randomised participants.

Severe or blood glucose (BG) confirmed symptomatic hypoglycaemic episodes were defined as episodes that were severe according to the American Diabetes Association (ADA) classification (required assistance of another person to actively administer carbohydrate, glucagon, or take other corrective actions) or BG confirmed by a plasma glucose value \<3.1 millimoles per liter (mmol/L) with symptoms consistent with hypoglycaemia. Hypoglycaemic episodes were defined as treatment-emergent if the onset of the episode occurred on or after the first day of trial product administration, and no later than the day after the last day on trial product. Participants who achieved HbA1c ≤7.0% without treatment emergent severe hypoglycaemic episodes or BG confirmed symptomatic hypoglycaemic episodes (yes/no) is presented.

Outcome measures

Outcome measures
Measure	Liraglutide 1.8 mg n=996 Participants Participants were to receive a subcutaneous injection of liraglutide once daily. Participants received 0.6 milligrams (mg) liraglutide during the first week. The dose was escalated in weekly increments of 0.6 mg until the dose of 1.8 mg was reached. The treatment period was 104 weeks.	Oral Antidiabetic Drug n=995 Participants Participants were to receive one selected OAD. The following OADs were allowed: alpha-glucosidase inhibitors, dipeptidyl peptidase-4 (DPP-4) inhibitors, meglitinides, sodium-glucose co-transporter-2 (SGLT-2) inhibitors, sulfonylureas or thiazolidinediones. The treatment period was 104 weeks.
Participants Who Achieve HbA1c ≤7.0% Without Treatment Emergent Severe Hypoglycaemic Episodes or BG Confirmed Symptomatic Hypoglycaemic Episodes Yes	388 Participants	292 Participants
Participants Who Achieve HbA1c ≤7.0% Without Treatment Emergent Severe Hypoglycaemic Episodes or BG Confirmed Symptomatic Hypoglycaemic Episodes No	608 Participants	703 Participants

SECONDARY outcome

Timeframe: Week 104/Premature treatment discontinuation

Population: FAS included all randomised participants.

Severe or BG confirmed symptomatic hypoglycaemic episodes were defined as episodes that were severe according to the ADA classification (required assistance of another person to actively administer carbohydrate, glucagon, or take other corrective actions) or BG confirmed by a plasma glucose value \<3.1 mmol/L with symptoms consistent with hypoglycaemia. Hypoglycaemic episodes were defined as treatment-emergent if the onset of the episode occurred on or after the first day of trial product administration, and no later than the day after the last day on trial product. Participants who achieved HbA1c ≤7.0% without weight gain and no treatment emergent severe hypoglycaemic episodes or BG confirmed symptomatic hypoglycaemic episodes (yes/no) is presented.

Outcome measures

Outcome measures
Measure	Liraglutide 1.8 mg n=996 Participants Participants were to receive a subcutaneous injection of liraglutide once daily. Participants received 0.6 milligrams (mg) liraglutide during the first week. The dose was escalated in weekly increments of 0.6 mg until the dose of 1.8 mg was reached. The treatment period was 104 weeks.	Oral Antidiabetic Drug n=995 Participants Participants were to receive one selected OAD. The following OADs were allowed: alpha-glucosidase inhibitors, dipeptidyl peptidase-4 (DPP-4) inhibitors, meglitinides, sodium-glucose co-transporter-2 (SGLT-2) inhibitors, sulfonylureas or thiazolidinediones. The treatment period was 104 weeks.
Participants Who Achieve HbA1c ≤7.0% Without Weight Gain and no Treatment Emergent Severe Hypoglycaemic Episodes or Blood Glucose Confirmed Symptomatic Hypoglycaemic Episodes Yes	320 Participants	227 Participants
Participants Who Achieve HbA1c ≤7.0% Without Weight Gain and no Treatment Emergent Severe Hypoglycaemic Episodes or Blood Glucose Confirmed Symptomatic Hypoglycaemic Episodes No	676 Participants	768 Participants

SECONDARY outcome

Timeframe: Week 0, week 104/premature treatment discontinuation

Population: Overall number of participants analyzed=FAS included all randomised participants. Number analyzed=participants with available data.

Change from baseline (week 0) in FPG at week 104 or at premature treatment discontinuation is presented.

Outcome measures

Outcome measures
Measure	Liraglutide 1.8 mg n=996 Participants Participants were to receive a subcutaneous injection of liraglutide once daily. Participants received 0.6 milligrams (mg) liraglutide during the first week. The dose was escalated in weekly increments of 0.6 mg until the dose of 1.8 mg was reached. The treatment period was 104 weeks.	Oral Antidiabetic Drug n=995 Participants Participants were to receive one selected OAD. The following OADs were allowed: alpha-glucosidase inhibitors, dipeptidyl peptidase-4 (DPP-4) inhibitors, meglitinides, sodium-glucose co-transporter-2 (SGLT-2) inhibitors, sulfonylureas or thiazolidinediones. The treatment period was 104 weeks.
Change in Fasting Plasma Glucose (FPG) Change at week 104	-2.2 Millimoles per liter (mmol/L) Standard Deviation 2.65	-1.2 Millimoles per liter (mmol/L) Standard Deviation 2.46
Change in Fasting Plasma Glucose (FPG) Change at premature treatment discontinuation	-0.6 Millimoles per liter (mmol/L) Standard Deviation 2.91	-0.6 Millimoles per liter (mmol/L) Standard Deviation 3.76

SECONDARY outcome

Timeframe: Week 0, week 104/premature treatment discontinuation

Population: Overall number of participants analyzed=FAS included all randomised participants. Number analyzed=participants with available data.

Change from baseline (week 0) in body weight at week 104 or at premature treatment discontinuation is presented.

Outcome measures

Outcome measures
Measure	Liraglutide 1.8 mg n=996 Participants Participants were to receive a subcutaneous injection of liraglutide once daily. Participants received 0.6 milligrams (mg) liraglutide during the first week. The dose was escalated in weekly increments of 0.6 mg until the dose of 1.8 mg was reached. The treatment period was 104 weeks.	Oral Antidiabetic Drug n=995 Participants Participants were to receive one selected OAD. The following OADs were allowed: alpha-glucosidase inhibitors, dipeptidyl peptidase-4 (DPP-4) inhibitors, meglitinides, sodium-glucose co-transporter-2 (SGLT-2) inhibitors, sulfonylureas or thiazolidinediones. The treatment period was 104 weeks.
Change in Body Weight Change at week 104	-3.8 Kilogram (Kg) Standard Deviation 6.38	-3.5 Kilogram (Kg) Standard Deviation 6.19
Change in Body Weight Change at premature treatment discontinuation	-2.9 Kilogram (Kg) Standard Deviation 3.74	-2.2 Kilogram (Kg) Standard Deviation 4.93

SECONDARY outcome

Timeframe: Week 0, week 104/premature treatment discontinuation

Population: Overall number of participants analyzed=FAS included all randomised participants. Number analyzed=participants with available data.

Change from baseline (week 0) in BMI at week 104 or at premature treatment discontinuation is presented.

Outcome measures

Outcome measures
Measure	Liraglutide 1.8 mg n=996 Participants Participants were to receive a subcutaneous injection of liraglutide once daily. Participants received 0.6 milligrams (mg) liraglutide during the first week. The dose was escalated in weekly increments of 0.6 mg until the dose of 1.8 mg was reached. The treatment period was 104 weeks.	Oral Antidiabetic Drug n=995 Participants Participants were to receive one selected OAD. The following OADs were allowed: alpha-glucosidase inhibitors, dipeptidyl peptidase-4 (DPP-4) inhibitors, meglitinides, sodium-glucose co-transporter-2 (SGLT-2) inhibitors, sulfonylureas or thiazolidinediones. The treatment period was 104 weeks.
Change in Body Mass Index (BMI) Change at week 104	-1.3 Kilograms per square meter (kg/m^2) Standard Deviation 2.26	-1.2 Kilograms per square meter (kg/m^2) Standard Deviation 2.14
Change in Body Mass Index (BMI) Change at premature treatment discontinuation	-1.1 Kilograms per square meter (kg/m^2) Standard Deviation 1.33	-0.8 Kilograms per square meter (kg/m^2) Standard Deviation 1.71

SECONDARY outcome

Timeframe: Week 0, week 104/premature treatment discontinuation

Population: Overall number of participants analyzed=FAS included all randomised participants. Number analyzed=participants with available data.

Change from baseline (week 0) in systolic and diastolic blood pressure at week 104 or at premature treatment discontinuation is presented.

Outcome measures

Outcome measures
Measure	Liraglutide 1.8 mg n=996 Participants Participants were to receive a subcutaneous injection of liraglutide once daily. Participants received 0.6 milligrams (mg) liraglutide during the first week. The dose was escalated in weekly increments of 0.6 mg until the dose of 1.8 mg was reached. The treatment period was 104 weeks.	Oral Antidiabetic Drug n=995 Participants Participants were to receive one selected OAD. The following OADs were allowed: alpha-glucosidase inhibitors, dipeptidyl peptidase-4 (DPP-4) inhibitors, meglitinides, sodium-glucose co-transporter-2 (SGLT-2) inhibitors, sulfonylureas or thiazolidinediones. The treatment period was 104 weeks.
Change in Blood Pressure (Systolic and Diastolic Blood Pressure) SBP: Change at week 104	-2.4 Millimeters of mercury (mmHg) Standard Deviation 15.09	-1.1 Millimeters of mercury (mmHg) Standard Deviation 15.11
Change in Blood Pressure (Systolic and Diastolic Blood Pressure) SBP: Change at premature treatment discontinuation	-2.8 Millimeters of mercury (mmHg) Standard Deviation 15.99	-2.9 Millimeters of mercury (mmHg) Standard Deviation 15.23
Change in Blood Pressure (Systolic and Diastolic Blood Pressure) DBP: Change at week 104	-1.3 Millimeters of mercury (mmHg) Standard Deviation 9.51	-0.6 Millimeters of mercury (mmHg) Standard Deviation 9.54
Change in Blood Pressure (Systolic and Diastolic Blood Pressure) DBP: Change at premature treatment discontinuation	-1.0 Millimeters of mercury (mmHg) Standard Deviation 11.27	0.2 Millimeters of mercury (mmHg) Standard Deviation 9.69

SECONDARY outcome

Timeframe: Weeks 0-104

Population: Safety analysis set (SAS) included all participants exposed to at least one dose of trial product.

Severe hypoglycaemic episodes were defined as episodes that required assistance of another person to actively administer carbohydrate, glucagon, or take other corrective actions. Number of severe hypoglycaemic episodes that occured during weeks 0-104 are presented.

Outcome measures

Outcome measures
Measure	Liraglutide 1.8 mg n=980 Participants Participants were to receive a subcutaneous injection of liraglutide once daily. Participants received 0.6 milligrams (mg) liraglutide during the first week. The dose was escalated in weekly increments of 0.6 mg until the dose of 1.8 mg was reached. The treatment period was 104 weeks.	Oral Antidiabetic Drug n=984 Participants Participants were to receive one selected OAD. The following OADs were allowed: alpha-glucosidase inhibitors, dipeptidyl peptidase-4 (DPP-4) inhibitors, meglitinides, sodium-glucose co-transporter-2 (SGLT-2) inhibitors, sulfonylureas or thiazolidinediones. The treatment period was 104 weeks.
Number of Severe Hypoglycaemic Episodes	32 Episodes	52 Episodes

SECONDARY outcome

Timeframe: Weeks 0-104

Population: SAS included all participants exposed to at least one dose of trial product.

Outcome measures

Outcome measures
Measure	Liraglutide 1.8 mg n=980 Participants Participants were to receive a subcutaneous injection of liraglutide once daily. Participants received 0.6 milligrams (mg) liraglutide during the first week. The dose was escalated in weekly increments of 0.6 mg until the dose of 1.8 mg was reached. The treatment period was 104 weeks.	Oral Antidiabetic Drug n=984 Participants Participants were to receive one selected OAD. The following OADs were allowed: alpha-glucosidase inhibitors, dipeptidyl peptidase-4 (DPP-4) inhibitors, meglitinides, sodium-glucose co-transporter-2 (SGLT-2) inhibitors, sulfonylureas or thiazolidinediones. The treatment period was 104 weeks.
Number of Severe or BG Confirmed Symptomatic Hypoglycaemic Episodes	24 Episodes	44 Episodes

SECONDARY outcome

Timeframe: Weeks 0-104

Population: SAS included all participants exposed to at least one dose of trial product.

Documented symptomatic hypoglycaemic were defined as episodes with typical symptoms of hypoglycaemia accompanied by measure plasma glucose concentration \<= 3.9 mmol/L. Number of documented symptomatic hypoglycaemic episodes that occured during the weeks 0-104 are presented.

Outcome measures

Outcome measures
Measure	Liraglutide 1.8 mg n=980 Participants Participants were to receive a subcutaneous injection of liraglutide once daily. Participants received 0.6 milligrams (mg) liraglutide during the first week. The dose was escalated in weekly increments of 0.6 mg until the dose of 1.8 mg was reached. The treatment period was 104 weeks.	Oral Antidiabetic Drug n=984 Participants Participants were to receive one selected OAD. The following OADs were allowed: alpha-glucosidase inhibitors, dipeptidyl peptidase-4 (DPP-4) inhibitors, meglitinides, sodium-glucose co-transporter-2 (SGLT-2) inhibitors, sulfonylureas or thiazolidinediones. The treatment period was 104 weeks.
Number of Documented Symptomatic Hypoglycaemic Episodes (ADA)	98 Episodes	155 Episodes

SECONDARY outcome

Timeframe: Weeks 0-105

Population: SAS included all participants exposed to at least one dose of trial product.

A serious adverse event (SAE) was defined as any event that resulted in any of the following: death, life-threatening experience, in-patient hospitalisation or prolongation of existing hospitalisation, persistent or significant disability or incapacity, congenital anomaly or birth defect or suspicion of transmission of infectious agents via the trial product. An SAE was considered as treatment emergent if it had an onset or increase in severity on or after the time of first trial product administration and no later than 7 days after the time of last trial product administration. Number of treatment emergent serious adverse events are presented.

Outcome measures

Outcome measures
Measure	Liraglutide 1.8 mg n=980 Participants Participants were to receive a subcutaneous injection of liraglutide once daily. Participants received 0.6 milligrams (mg) liraglutide during the first week. The dose was escalated in weekly increments of 0.6 mg until the dose of 1.8 mg was reached. The treatment period was 104 weeks.	Oral Antidiabetic Drug n=984 Participants Participants were to receive one selected OAD. The following OADs were allowed: alpha-glucosidase inhibitors, dipeptidyl peptidase-4 (DPP-4) inhibitors, meglitinides, sodium-glucose co-transporter-2 (SGLT-2) inhibitors, sulfonylureas or thiazolidinediones. The treatment period was 104 weeks.
Number of Serious Adverse Events (SAEs)	145 Events	140 Events

SECONDARY outcome

Timeframe: Weeks 0-105

Population: SAS included all participants exposed to at least one dose of trial product.

An adverse event (AE) was any untoward medical occurrence in a participant who administered a product, and which did not necessarily had a causal relationship with this treatment. An AE was considered as treatment emergent if it had an onset or increase in severity on or after the time of first trial product administration and no later than 7 days after the time of last trial product administration. Number of treatment emergent AEs that led to permanent discontinuation of trial product are presented.

Outcome measures

Outcome measures
Measure	Liraglutide 1.8 mg n=980 Participants Participants were to receive a subcutaneous injection of liraglutide once daily. Participants received 0.6 milligrams (mg) liraglutide during the first week. The dose was escalated in weekly increments of 0.6 mg until the dose of 1.8 mg was reached. The treatment period was 104 weeks.	Oral Antidiabetic Drug n=984 Participants Participants were to receive one selected OAD. The following OADs were allowed: alpha-glucosidase inhibitors, dipeptidyl peptidase-4 (DPP-4) inhibitors, meglitinides, sodium-glucose co-transporter-2 (SGLT-2) inhibitors, sulfonylureas or thiazolidinediones. The treatment period was 104 weeks.
Number of AEs Leading to Permanent Discontinuation of Trial Product	188 Events	98 Events

SECONDARY outcome

Timeframe: Week 0, week 104/premature treatment discontinuation

Population: Overall number of participants analyzed=SAS included all participants exposed to at least one dose of trial product. Number analyzed=participants with available data.

Change from baseline (week 0) in high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, total cholesterol (TC) and triglycerides (TG) at week 104 or at premature treatment discontinuation is presented.

Outcome measures

Outcome measures
Measure	Liraglutide 1.8 mg n=980 Participants Participants were to receive a subcutaneous injection of liraglutide once daily. Participants received 0.6 milligrams (mg) liraglutide during the first week. The dose was escalated in weekly increments of 0.6 mg until the dose of 1.8 mg was reached. The treatment period was 104 weeks.	Oral Antidiabetic Drug n=984 Participants Participants were to receive one selected OAD. The following OADs were allowed: alpha-glucosidase inhibitors, dipeptidyl peptidase-4 (DPP-4) inhibitors, meglitinides, sodium-glucose co-transporter-2 (SGLT-2) inhibitors, sulfonylureas or thiazolidinediones. The treatment period was 104 weeks.
Change in Lipids: HDL Cholesterol, LDL-cholesterol, Total Cholesterol, Triglycerides HDL: Change at week 104	0.1 Millimoles per liter (mmol/L) Standard Deviation 0.20	0.1 Millimoles per liter (mmol/L) Standard Deviation 0.19
Change in Lipids: HDL Cholesterol, LDL-cholesterol, Total Cholesterol, Triglycerides HDL: Change at premature treatment discontinuation	-0.0 Millimoles per liter (mmol/L) Standard Deviation 0.17	0.0 Millimoles per liter (mmol/L) Standard Deviation 0.20
Change in Lipids: HDL Cholesterol, LDL-cholesterol, Total Cholesterol, Triglycerides LDL: Change at week 104	-0.1 Millimoles per liter (mmol/L) Standard Deviation 0.80	0.0 Millimoles per liter (mmol/L) Standard Deviation 0.83
Change in Lipids: HDL Cholesterol, LDL-cholesterol, Total Cholesterol, Triglycerides LDL: Change at premature treatment discontinuation	-0.1 Millimoles per liter (mmol/L) Standard Deviation 0.68	-0.1 Millimoles per liter (mmol/L) Standard Deviation 0.85
Change in Lipids: HDL Cholesterol, LDL-cholesterol, Total Cholesterol, Triglycerides TC: Change at week 104	-0.2 Millimoles per liter (mmol/L) Standard Deviation 0.92	0.1 Millimoles per liter (mmol/L) Standard Deviation 0.99
Change in Lipids: HDL Cholesterol, LDL-cholesterol, Total Cholesterol, Triglycerides TC: Change at premature treatment discontinuation	-0.0 Millimoles per liter (mmol/L) Standard Deviation 0.81	-0.1 Millimoles per liter (mmol/L) Standard Deviation 0.96
Change in Lipids: HDL Cholesterol, LDL-cholesterol, Total Cholesterol, Triglycerides TG: Change at week 104	-0.3 Millimoles per liter (mmol/L) Standard Deviation 0.95	-0.1 Millimoles per liter (mmol/L) Standard Deviation 1.25
Change in Lipids: HDL Cholesterol, LDL-cholesterol, Total Cholesterol, Triglycerides TG: Change at premature treatment discontinuation	-0.0 Millimoles per liter (mmol/L) Standard Deviation 1.13	-0.0 Millimoles per liter (mmol/L) Standard Deviation 1.30

SECONDARY outcome

Timeframe: Week 0, week 104/premature treatment discontinuation

Population: Overall number of participants analyzed=SAS included all participants exposed to at least one dose of trial product. Number analyzed=participants with available data.

Change from baseline (week 0) in alanine aminotransferase (ALAT), amylase, aspartate aminotransferase (ASAT) and lipase at week 104 or at premature treatment discontinuation is presented.

Outcome measures

Outcome measures
Measure	Liraglutide 1.8 mg n=980 Participants Participants were to receive a subcutaneous injection of liraglutide once daily. Participants received 0.6 milligrams (mg) liraglutide during the first week. The dose was escalated in weekly increments of 0.6 mg until the dose of 1.8 mg was reached. The treatment period was 104 weeks.	Oral Antidiabetic Drug n=984 Participants Participants were to receive one selected OAD. The following OADs were allowed: alpha-glucosidase inhibitors, dipeptidyl peptidase-4 (DPP-4) inhibitors, meglitinides, sodium-glucose co-transporter-2 (SGLT-2) inhibitors, sulfonylureas or thiazolidinediones. The treatment period was 104 weeks.
Change in Biochemistry- Alanine Aminotransferase (ALAT), Amylase, Aspartate Aminotransferase (ASAT), Lipase ASAT: Week 104	-2.0 Units per liter (U/L) Standard Deviation 13.27	-2.3 Units per liter (U/L) Standard Deviation 11.85
Change in Biochemistry- Alanine Aminotransferase (ALAT), Amylase, Aspartate Aminotransferase (ASAT), Lipase ASAT: Premature treatment discontinuation	-1.9 Units per liter (U/L) Standard Deviation 10.76	-0.4 Units per liter (U/L) Standard Deviation 11.64
Change in Biochemistry- Alanine Aminotransferase (ALAT), Amylase, Aspartate Aminotransferase (ASAT), Lipase Lipase: Week 104	15.1 Units per liter (U/L) Standard Deviation 67.69	-0.5 Units per liter (U/L) Standard Deviation 50.03
Change in Biochemistry- Alanine Aminotransferase (ALAT), Amylase, Aspartate Aminotransferase (ASAT), Lipase Lipase: Premature treatment discontinuation	10.4 Units per liter (U/L) Standard Deviation 32.40	-2.2 Units per liter (U/L) Standard Deviation 35.79
Change in Biochemistry- Alanine Aminotransferase (ALAT), Amylase, Aspartate Aminotransferase (ASAT), Lipase ALAT: Week 104	-4.6 Units per liter (U/L) Standard Deviation 17.83	-5.4 Units per liter (U/L) Standard Deviation 17.13
Change in Biochemistry- Alanine Aminotransferase (ALAT), Amylase, Aspartate Aminotransferase (ASAT), Lipase ALAT: Premature treatment discontinuation	-3.2 Units per liter (U/L) Standard Deviation 12.44	-3.3 Units per liter (U/L) Standard Deviation 14.67
Change in Biochemistry- Alanine Aminotransferase (ALAT), Amylase, Aspartate Aminotransferase (ASAT), Lipase Amylase: Week 104	8.9 Units per liter (U/L) Standard Deviation 30.93	5.1 Units per liter (U/L) Standard Deviation 26.30
Change in Biochemistry- Alanine Aminotransferase (ALAT), Amylase, Aspartate Aminotransferase (ASAT), Lipase Amylase: Premature treatment discontinuation	0.6 Units per liter (U/L) Standard Deviation 23.61	2.1 Units per liter (U/L) Standard Deviation 17.92

SECONDARY outcome

Timeframe: Week 0, week 104/premature treatment discontinuation

Population: Overall number of participants analyzed=SAS included all participants exposed to at least one dose of trial product. Number analyzed=participants with available data.

Change from baseline (week 0) in creatinine and total bilirubin (TB) at week 104 or at premature treatment discontinuation is presented.

Outcome measures

Outcome measures
Measure	Liraglutide 1.8 mg n=980 Participants Participants were to receive a subcutaneous injection of liraglutide once daily. Participants received 0.6 milligrams (mg) liraglutide during the first week. The dose was escalated in weekly increments of 0.6 mg until the dose of 1.8 mg was reached. The treatment period was 104 weeks.	Oral Antidiabetic Drug n=984 Participants Participants were to receive one selected OAD. The following OADs were allowed: alpha-glucosidase inhibitors, dipeptidyl peptidase-4 (DPP-4) inhibitors, meglitinides, sodium-glucose co-transporter-2 (SGLT-2) inhibitors, sulfonylureas or thiazolidinediones. The treatment period was 104 weeks.
Change in Biochemistry- Creatinine, Total Bilirubin Creatinine: week 104	3.3 Micromoles per liter (umol/L) Standard Deviation 13.37	1.0 Micromoles per liter (umol/L) Standard Deviation 12.86
Change in Biochemistry- Creatinine, Total Bilirubin Creatinine: premature treatment discontinuation	2.9 Micromoles per liter (umol/L) Standard Deviation 12.06	2.6 Micromoles per liter (umol/L) Standard Deviation 21.13
Change in Biochemistry- Creatinine, Total Bilirubin TB: week 104	0.4 Micromoles per liter (umol/L) Standard Deviation 4.47	0.7 Micromoles per liter (umol/L) Standard Deviation 3.80
Change in Biochemistry- Creatinine, Total Bilirubin TB: premature treatment discontinuation	-0.0 Micromoles per liter (umol/L) Standard Deviation 2.78	-0.6 Micromoles per liter (umol/L) Standard Deviation 3.17

SECONDARY outcome

Timeframe: Week 0, week 104/premature treatment discontinuation

Population: Overall number of participants analyzed=SAS included all participants exposed to at least one dose of trial product. Number analyzed=participants with available data.

The estimated GFR was derived from serum creatinine using the MDRD (Modification of diet in renal disease) formula. eGFR was measured as milliliter per min per specific surface area (mL/min/SSA).

Outcome measures

Outcome measures
Measure	Liraglutide 1.8 mg n=980 Participants Participants were to receive a subcutaneous injection of liraglutide once daily. Participants received 0.6 milligrams (mg) liraglutide during the first week. The dose was escalated in weekly increments of 0.6 mg until the dose of 1.8 mg was reached. The treatment period was 104 weeks.	Oral Antidiabetic Drug n=984 Participants Participants were to receive one selected OAD. The following OADs were allowed: alpha-glucosidase inhibitors, dipeptidyl peptidase-4 (DPP-4) inhibitors, meglitinides, sodium-glucose co-transporter-2 (SGLT-2) inhibitors, sulfonylureas or thiazolidinediones. The treatment period was 104 weeks.
Change in Biochemistry- Estimated Glomerular Filtration Rate (eGFR) Serum Change at week 104	-5.1 mL/min/SSA Standard Deviation 20.33	-1.6 mL/min/SSA Standard Deviation 16.29
Change in Biochemistry- Estimated Glomerular Filtration Rate (eGFR) Serum Change at premature treatment discontinuation	-3.0 mL/min/SSA Standard Deviation 12.56	-1.7 mL/min/SSA Standard Deviation 15.01

SECONDARY outcome

Timeframe: Week 0, week 104/premature treatment discontinuation

Population: Overall number of participants analyzed=SAS included all participants exposed to at least one dose of trial product. Number analyzed=participants with available data.

Change from baseline (week 0) in potassium at week 104 or at premature treatment discontinuation is presented.

Outcome measures

Outcome measures
Measure	Liraglutide 1.8 mg n=980 Participants Participants were to receive a subcutaneous injection of liraglutide once daily. Participants received 0.6 milligrams (mg) liraglutide during the first week. The dose was escalated in weekly increments of 0.6 mg until the dose of 1.8 mg was reached. The treatment period was 104 weeks.	Oral Antidiabetic Drug n=984 Participants Participants were to receive one selected OAD. The following OADs were allowed: alpha-glucosidase inhibitors, dipeptidyl peptidase-4 (DPP-4) inhibitors, meglitinides, sodium-glucose co-transporter-2 (SGLT-2) inhibitors, sulfonylureas or thiazolidinediones. The treatment period was 104 weeks.
Change in Potassium Change at week 104	-0.1 Millimoles per liter (mmol/L) Standard Deviation 0.60	-0.0 Millimoles per liter (mmol/L) Standard Deviation 0.59
Change in Potassium Change at premature treatment discontinuation	-0.0 Millimoles per liter (mmol/L) Standard Deviation 0.44	-0.2 Millimoles per liter (mmol/L) Standard Deviation 0.71

SECONDARY outcome

Timeframe: Week 0, week 104/premature treatment discontinuation

Population: Overall number of participants analyzed=SAS included all participants exposed to at least one dose of trial product. Number analyzed=participants with available data.

Change from baseline (week 0) in haemoglobin at week 104 or at premature treatment discontinuation is presented.

Outcome measures

Outcome measures
Measure	Liraglutide 1.8 mg n=980 Participants Participants were to receive a subcutaneous injection of liraglutide once daily. Participants received 0.6 milligrams (mg) liraglutide during the first week. The dose was escalated in weekly increments of 0.6 mg until the dose of 1.8 mg was reached. The treatment period was 104 weeks.	Oral Antidiabetic Drug n=984 Participants Participants were to receive one selected OAD. The following OADs were allowed: alpha-glucosidase inhibitors, dipeptidyl peptidase-4 (DPP-4) inhibitors, meglitinides, sodium-glucose co-transporter-2 (SGLT-2) inhibitors, sulfonylureas or thiazolidinediones. The treatment period was 104 weeks.
Change in Haemoglobin Change at week 104	-0.4 Grams per deciliter (g/dL) Standard Deviation 1.07	-0.0 Grams per deciliter (g/dL) Standard Deviation 1.16
Change in Haemoglobin Change at premature treatment discontinuation	-0.3 Grams per deciliter (g/dL) Standard Deviation 0.87	-0.3 Grams per deciliter (g/dL) Standard Deviation 1.12

SECONDARY outcome

Timeframe: Week 0, week 104/premature treatment discontinuation

Population: Overall number of participants analyzed=SAS included all participants exposed to at least one dose of trial product. Number analyzed=participants with available data.

Change from baseline (week 0) in pulse at week 104 or at premature treatment discontinuation is presented.

Outcome measures

Outcome measures
Measure	Liraglutide 1.8 mg n=980 Participants Participants were to receive a subcutaneous injection of liraglutide once daily. Participants received 0.6 milligrams (mg) liraglutide during the first week. The dose was escalated in weekly increments of 0.6 mg until the dose of 1.8 mg was reached. The treatment period was 104 weeks.	Oral Antidiabetic Drug n=984 Participants Participants were to receive one selected OAD. The following OADs were allowed: alpha-glucosidase inhibitors, dipeptidyl peptidase-4 (DPP-4) inhibitors, meglitinides, sodium-glucose co-transporter-2 (SGLT-2) inhibitors, sulfonylureas or thiazolidinediones. The treatment period was 104 weeks.
Change in Pulse Change at week 104	1.0 Beats per minute (beats/min) Standard Deviation 10.25	-0.6 Beats per minute (beats/min) Standard Deviation 10.23
Change in Pulse Change at premature treatment discontinuation	0.7 Beats per minute (beats/min) Standard Deviation 9.84	0.9 Beats per minute (beats/min) Standard Deviation 10.59

Adverse Events

Liraglutide 1.8 mg

Serious events: 92 serious events

Other events: 65 other events

Deaths: 1 deaths

Oral Antidiabetic Drug

Serious events: 81 serious events

Other events: 15 other events

Deaths: 8 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Liraglutide 1.8 mg n=980 participants at risk Participants were to receive a subcutaneous injection of liraglutide once daily. Participants received 0.6 milligrams (mg) liraglutide during the first week. The dose was escalated in weekly increments of 0.6 mg until the dose of 1.8 mg was reached. The treatment period was 104 weeks.	Oral Antidiabetic Drug n=984 participants at risk Participants were to receive one selected OAD. The following OADs were allowed: alpha-glucosidase inhibitors, dipeptidyl peptidase-4 (DPP-4) inhibitors, meglitinides, sodium-glucose co-transporter-2 (SGLT-2) inhibitors, sulfonylureas or thiazolidinediones. The treatment period was 104 weeks.
Gastrointestinal disorders Nausea	6.6% 65/980 • Number of events 82 • Weeks 0-105 All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants exposed to at least one dose of trial product.	1.5% 15/984 • Number of events 21 • Weeks 0-105 All presented AEs are TEAEs. A TEAE was defined as an event that had onset date on or after the first day of exposure to trial product and no later than 7 days after the last day of trial product administration. Results are based on the SAS which included all participants exposed to at least one dose of trial product.

Additional Information

Clinical Reporting Anchor and Disclosure (1452)

Novo Nordisk A/S

Phone: (+1) 866-867-7178

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee At the end of the trial, one or more scientific publications may be prepared collaboratively by the investigator(s) and Novo Nordisk. Novo Nordisk reserves the right to postpone publication and/or communication for up to 60 days to protect intellectual property.
Publication restrictions are in place

Restriction type: OTHER