NCT02964247

LIRA-ADD2SGLT2i - Liraglutide Versus Placebo as add-on to SGLT2 Inhibitors.

Completed Phase 3 Results posted Last updated 17 November 2020

What this trial tests

Phase 3 trial testing liraglutide in Diabetes in 303 participants. Completed in 8 May 2018.

Timeline

3 March 2017

Primary endpoint
4 May 2018

8 May 2018

Quick facts

Lead sponsor	Novo Nordisk A/S
Phase	Phase 3
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	double
Primary purpose	treatment
Enrollment	303
Start date	3 March 2017
Primary completion	4 May 2018
Estimated completion	8 May 2018
Sites	82 locations across Russia, Israel, United Arab Emirates, Puerto Rico, United States, Brazil, India

Drugs / interventions tested

• liraglutide (liraglutide) — full drug profile →
• placebo

Conditions studied

• Diabetes — all drugs for Diabetes →
• Diabetes Mellitus, Type 2 — all drugs for Diabetes Mellitus, Type 2 →

Sponsor

Novo Nordisk A/S — full company profile →

Who can join

18 and older, any sex, with Diabetes or Diabetes Mellitus, Type 2. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Change in HbA1c Primary · Week 0, Week 26

Change from baseline (week 0) to week 26 in glycosylated haemoglobin was evaluated for 2 different observation period 'in-trial' observation period and 'on-treatment without rescue medication" observation period. The 'in-trial' observation period represents the time-period where subjects were considered to be in the trial, regardless of whether or not the subjects had initiated rescue medication or prematurely discontinued trial product. The 'on-treatment' observation period is the part of the in-trial observation period during which subjects were treated with the trial product, that is the ti

in-trial obs. period

Group	Value	95% CI
Liraglutide	-1.00	± 0.86
Placebo	-0.32	± 0.83

on-treatment without rescue medication obs. period

Group	Value	95% CI
Liraglutide	-1.05	± 0.85
Placebo	-0.35	± 0.80

Change in Body Weight Secondary · Week 0, Week 26

Change from baseline (week 0) to week 26 in body weight was evaluated for 2 different observation period 'in-trial' observation period and 'on-treatment without rescue medication" observation period. The 'in-trial' observation period represents the time-period where subjects were considered to be in the trial, regardless of whether or not the subjects had initiated rescue medication or prematurely discontinued trial product. The 'on-treatment' observation period is the part of the in-trial observation period during which subjects were treated with the trial product, that is the time from the f

in-trial obs. period

Group	Value	95% CI
Liraglutide	-2.84	± 3.83
Placebo	-2.02	± 3.32

on-treatment without rescue medication obs. period

Group	Value	95% CI
Liraglutide	-2.89	± 3.81
Placebo	-2.09	± 2.96

Change in Fasting Plasma Glucose Secondary · Week 0, Week 26

Change from baseline (week 0) to week 26 in fasting plasma glucose ('in-trial' observation period)

Group	Value	95% CI
Liraglutide	-27.00	± 35.01
Placebo	-11.97	± 45.20

Subjects Who Achieve HbA1c Below 7.0% (53 mmol/Mol), American Diabetes Association Target Secondary · Week 26

Percentage of subjects who achieve HbA1c below 7.0% (53 mmol/mol), American Diabetes Association target, after 26 weeks ('in-trial' observation period)

Yes

Group	Value	95% CI
Liraglutide	51.79
Placebo	23.16

No

Group	Value	95% CI
Liraglutide	48.21
Placebo	76.84

Subjects Who Achieve HbA1c Below or Equal to 6.5% (48 mmol/Mol), American Association of Clinical Endocrinologists Target Secondary · Week 26

Percentage of subjects who achieve HbA1c below or equal to 6.5% (48 mmol/mol), American Association of Clinical Endocrinologists target, after 26 weeks ('in-trial' observation period)

Yes

Group	Value	95% CI
Liraglutide	34.36
Placebo	9.47

No

Group	Value	95% CI
Liraglutide	65.64
Placebo	90.53

Subjects Who Achieve HbA1c Below 7.0% (53 mmol/Mol) Without Severe or Blood Glucose Confirmed Symptomatic Hypoglycaemia Episodes and no Weight Gain. Secondary · Week 26

Percentage of subjects who achieve HbA1c below 7.0% (53 mmol/mol) without severe or blood glucose confirmed symptomatic hypoglycaemia episodes and no weight gain, after 26 weeks ('in-trial' observation period)

Yes

Group	Value	95% CI
Liraglutide	47.69
Placebo	19.15

No

Group	Value	95% CI
Liraglutide	52.31
Placebo	80.85

Subjects Who Achieve HbA1c Reduction Above or Equal to 1% (11mmol/Mol) and Weight Loss Above or Equal to 3%. Secondary · Week 26

Percentage of subjects who achieve HbA1c reduction above or equal to 1% (11mmol/mol) and weight loss above or equal to 3%, after 26 weeks ('in-trial' observation period)

Yes

Group	Value	95% CI
Liraglutide	29.74
Placebo	7.45

No

Group	Value	95% CI
Liraglutide	70.26
Placebo	92.55

Change in Self-measured Plasma Glucose 7-point Profile - Mean 7-point Profile Secondary · Week 0, Week 26

Change in self-measured plasma glucose 7-point profile - mean 7-point profile after 26 weeks. Subjects were instructed to measure their plasma glucose at following 7 timepoints: before breakfast, 90 minutes after start of breakfast, before lunch, 90 minutes after start of lunch, before dinner, 90 minutes after start of dinner, at bedtime. Mean of the 7-point profile was calculated ('in-trial' observation period).

Group	Value	95% CI
Liraglutide	-33.93	± 37.17
Placebo	-18.85	± 40.81

Change in Self-measured Plasma Glucose 7-point Profile - Mean Post Prandial Increments (Over All Meals) Secondary · Week 0, Week 26

Subjects were instructed to measure their plasma glucose at following 7 timepoints: before breakfast, 90 minutes after start of breakfast, before lunch, 90 minutes after start of lunch, before dinner, 90 minutes after start of dinner, at bedtime. The mean increment over all meals was derived as the mean of all available meal increments ('in-trial' observation period)

Group	Value	95% CI
Liraglutide	-11.06	± 41.29
Placebo	-4.44	± 44.77

Change in Body Mass Index (BMI) Secondary · Week 0, Week 26

Observed mean change from baseline (week 0) to week 26 in body mass index (BMI). BMI was calculated based on body weight and height ('in-trial' observation period)

Group	Value	95% CI
Liraglutide	-1.02	± 1.40
Placebo	-0.72	± 1.20

Subjects Who Achieve HbA1c Below 7.0% (53 mmol/Mol) and no Weight Gain Secondary · Week 26

Percentage of subjects who achieve HbA1c below 7.0% (53 mmol/mol) and no weight gain, after 26 week ('in-trial' observation period).

Yes

Group	Value	95% CI
Liraglutide	47.69
Placebo	19.15

No

Group	Value	95% CI
Liraglutide	52.31
Placebo	80.85

Subjects Who Achieve HbA1c Below 7.0% (53 mmol/Mol), no Weight Gain and Systolic Blood Pressure Below 140 mmHg. Secondary · Week 26

Percentage of subjects who achieve HbA1c below 7.0% (53 mmol/mol), no weight gain and systolic blood pressure below 140 mmHg, after 26 weeks ('in-trial' observation period)

Yes

Group	Value	95% CI
Liraglutide	42.05
Placebo	18.09

No

Group	Value	95% CI
Liraglutide	57.95
Placebo	81.91

Adverse events — posted to ClinicalTrials.gov

Time frame: Week 0 (randomisation visit) to week 26 (end-of-treatment visit) + 7 days. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Liraglutide

Serious: 5/202 (2%)

Deaths: 0/202

Placebo

Serious: 1/100 (1%)

Deaths: 0/100

Serious adverse events (9 terms)

Reaction	System	Liraglutide	Placebo
Acute kidney injury	Renal and urinary disorders	—	—
Angina unstable	Cardiac disorders	—	—
Cardiac failure congestive	Cardiac disorders	—	—
Cholecystitis	Hepatobiliary disorders	—	—
Congestive cardiomyopathy	Cardiac disorders	—	—
Eyelid cyst	Eye disorders	—	—
Haemorrhoids	Gastrointestinal disorders	—	—
Lower gastrointestinal haemorrhage	Gastrointestinal disorders	—	—
Ureterolithiasis	Renal and urinary disorders	—	—

Other adverse events (5 terms — click to expand)

Reaction	System	Liraglutide	Placebo
Nausea	Gastrointestinal disorders	—	—
Decreased appetite	Metabolism and nutrition disorders	—	—
Diarrhoea	Gastrointestinal disorders	—	—
Constipation	Gastrointestinal disorders	—	—
Vomiting	Gastrointestinal disorders	—	—

Most-reported serious reactions: Acute kidney injury, Angina unstable, Cardiac failure congestive, Cholecystitis, Congestive cardiomyopathy, Eyelid cyst, Haemorrhoids, Lower gastrointestinal haemorrhage.

Data from ClinicalTrials.gov NCT02964247 adverse events section.

Sponsor's own description

The trial is conducted in Asia, Europe, North America and South America. The aim of the study is to compare the effect of liraglutide 1.8 mg/day versus placebo as add-on to an SGLT2 inhibitor with or without metformin on glycaemic control in subjects with type 2 diabetes mellitus.

Publications & conference data

No peer-reviewed publications indexed yet for this trial. Completed trials usually publish results within 12-18 months.