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Trial · Interventional

CompletedPhase 3Results postedRegistry data

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

NCTNCT02964247 (opens ClinicalTrials.gov in a new tab)Other idNN2211-4315Other idU1111-1184-8086
Open at ClinicalTrials.govAsk about this trial

Overview

Status
Completed
Phase
Phase 3
Enrollment
303 participants (actual)
Sponsor
Novo Nordisk A/S · Industry
Design
Randomized · Double masking
Countries
7 countries

United States, Brazil, India, Israel, Puerto Rico, Russia, United Arab Emirates

Start
3 Mar 2017
Primary completion
4 May 2018
Completion
8 May 2018
First posted
16 Nov 2016 (estimated)
Last update posted
17 Nov 2020
Conditions
Diabetes · Diabetes Mellitus, Type 2

Timeline

1 trial · 1 completed · 1 with posted results

  • Completed
  • Ongoing
  • Not yet recruiting
  • Stopped
  • Estimated dates (est.)
  • Results posted
201720182019
  1. Ph 3

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

    NCT02964247

    3 Mar 2017 to 8 May 2018

Registry summary

Text and fields below are the sponsor's entries at ClinicalTrials.gov, shown as posted.

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.

Interventions

  • liraglutideDrug
  • placeboDrug

Arms2

  • Experimental

    liraglutide + SGLT2i ± metformin

  • Placebo comparator

    liraglutide placebo + SGLT2i ± metformin

Primary outcomes1

Outcomes the sponsor listed as primary.

  1. Change in HbA1c

    Time frame · Week 0, Week 26

    Registry description

    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 time from the first dose to the last dose of trial product. The 'on-treatment without rescue medication' observation period is a part of 'on-treatment' observation period during which subjects were considered treated with trial product and had not initiated any rescue medications.

Secondary outcomes(20)

  1. Change in Body Weight

    Time frame · Week 0, Week 26

    Registry description

    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 first dose to the last dose of trial product. The 'on-treatment without rescue medication' observation period is a part of 'on-treatment' observation period during which subjects were considered treated with trial product and had not initiated any rescue medications.

  2. Change in Fasting Plasma Glucose

    Time frame · Week 0, Week 26

    Registry description

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

  3. Subjects Who Achieve HbA1c Below 7.0% (53 mmol/Mol), American Diabetes Association Target

    Time frame · Week 26

    Registry description

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

  4. Subjects Who Achieve HbA1c Below or Equal to 6.5% (48 mmol/Mol), American Association of Clinical Endocrinologists Target

    Time frame · Week 26

    Registry description

    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)

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

    Time frame · Week 26

    Registry description

    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)

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

    Time frame · Week 26

    Registry description

    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)

  7. Change in Self-measured Plasma Glucose 7-point Profile - Mean 7-point Profile

    Time frame · Week 0, Week 26

    Registry description

    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).

  8. Change in Self-measured Plasma Glucose 7-point Profile - Mean Post Prandial Increments (Over All Meals)

    Time frame · Week 0, Week 26

    Registry description

    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)

  9. Change in Body Mass Index (BMI)

    Time frame · Week 0, Week 26

    Registry description

    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)

  10. Subjects Who Achieve HbA1c Below 7.0% (53 mmol/Mol) and no Weight Gain

    Time frame · Week 26

    Registry description

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

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

    Time frame · Week 26

    Registry description

    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)

  12. Subjects Who Achieve HbA1c Reduction Above or Equal to 1% (11mmol/Mol)

    Time frame · Week 26

    Registry description

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

  13. Subjects Who Achieve HbA1c Reduction Above or Equal to 1% (11mmol/Mol) and no Weight Gain

    Time frame · Week 26

    Registry description

    Percentage of subjects who achieve HbA1c reduction above or equal to 1% (11mmol/mol) and no weight gain, after 26 weeks.

  14. Number of Treatment Emergent Adverse Events

    Time frame · Week 0 - 26 + 7 days

    Registry description

    The on-treatment summary of adverse events includes treatment-emergent events with onset on or after the first day of exposure to randomised treatment and no later than the minimum of the date of the follow-up visit or the last day of randomised treatment + 7 days or the date of last subject-investigator contact.

  15. Number of Treatment Emergent Severe or Blood Glucose Confirmed Symptomatic Hypoglycaemia Episodes

    Time frame · Week 0 - 26

    Registry description

    Treatment emergent hypoglycaemic episode is defined episode with onset on or after the first day of exposure to randomised treatment and no later than the minimum of the date of the follow-up visit or the last day of randomised treatment + 1 days or the date of last subject-investigator contact. Severe or BG confirmed symptomatic hypoglycaemic episodes were defined as episodes that were severe according to American Diabetes Association's (ADA) classification or blood glucose confirmed by a plasma glucose value \< 3.1 mmol/L (56 mg/dL) with symptoms consistent with hypoglycaemia. Severe hypoglycaemia according to the ADA definition: an episode requiring assistance of another person to actively administer carbohydrate, glucagon, or take other corrective actions.

  16. Change in Fasting Blood Lipids - Total Cholesterol

    Time frame · Week 0, Week 26

    Registry description

    Fasting total cholesterol measured in mg/dL. Observed mean change in fasting total cholesterol from baseline (week 0) to week 26 is presented as ratio to baseline value.

  17. Change in Fasting Blood Lipids - Low Density Lipoprotein (LDL) Cholesterol

    Time frame · Week 0, Week 26

    Registry description

    Low density lipoprotein (LDL) cholesterol measured in mg/dL. Observed mean change in fasting low density lipoprotein cholesterol from baseline (week 0) to week 26 is presented as ratio to baseline value.

  18. Change in Fasting Blood Lipids - High Density Lipoprotein (HDL) Cholesterol

    Time frame · Week 0, Week 26

    Registry description

    High density lipoprotein (HDL) cholesterol measured in mg/dL. Observed mean change in fasting high density lipoprotein cholesterol from baseline (week 0) to week 26 is presented as ratio to baseline value.

  19. Change in Fasting Blood Lipids - Very Low Density Lipoprotein (VLDL) Cholesterol

    Time frame · Week 0, Week 26

    Registry description

    Very low density lipoprotein (VLDL) cholesterol measured in mg/dL. Observed mean change in fasting very low density lipoprotein cholesterol from baseline (week 0) to week 26 is presented as ratio to baseline value.

  20. Change in Fasting Blood Lipids-triglycerides

    Time frame · Week 0, Week 26

    Registry description

    Fasting triglycerides measured in mg/dL. Observed mean change in fasting triglycerides from baseline (week 0) to week 26 is presented as ratio to baseline value.

Posted results

Values are shown as posted at ClinicalTrials.gov, with their units. PepBank has not converted, pooled or compared them.

Primary outcome results

Primary outcomeMean· Week 0, Week 26

Change in HbA1c

GroupValue (Percentage of HbA1c)Spread
Liraglutide-1.000.86
Placebo-0.320.83
Secondary and other outcome results(7)
Secondary outcomeMean· Week 0, Week 26

Change in Body Weight

GroupValue (Kg)Spread
Liraglutide-2.843.83
Placebo-2.023.32
Secondary outcomeMean· Week 0, Week 26

Change in Fasting Plasma Glucose

GroupValue (milligram/dL)Spread
Liraglutide-27.0035.01
Placebo-11.9745.20
Secondary outcomeNumber· Week 26

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

GroupValue (Percentage of Participants)
Liraglutide51.79
Placebo23.16
Secondary outcomeNumber· Week 26

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

GroupValue (Percentage of Participants)
Liraglutide34.36
Placebo9.47
Secondary outcomeNumber· Week 26

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

GroupValue (Percentage of Participants)
Liraglutide47.69
Placebo19.15
Secondary outcomeNumber· Week 26

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

GroupValue (Percentage of Participants)
Liraglutide29.74
Placebo7.45
Secondary outcomeMean· Week 0, Week 26

Change in Self-measured Plasma Glucose 7-point Profile - Mean 7-point Profile

GroupValue (milligram/dL)Spread
Liraglutide-33.9337.17
Placebo-18.8540.81

Adverse events, as posted

Adverse events as posted: participants affected out of participants at risk, by group
GroupDeathsSerious eventsOther events
LiraglutideEligible subjects were given liraglutide subcutaneously (s.c.), once daily (OD) for 26 weeks. Subjects received 0.6 mg dose of liraglutide in week 1, dose was escalated to 1.2 mg in week 2 and 1.8 mg in week 3. Subjects remained on the stable dose of 1.8 mg liraglutide from week 3 to 26. Subjects continued their pre-trial SGLT2 inhibitor as monotherapy or in combination with metformin at stable pre-trial dose. Any one of three SGLT2 inhibitors were allowed as pre-trial therapy: Invokana®, Farxiga®/Forxiga® and Jardiance®. Stable pre-trial treatment with metformin was defined as ≥1500 mg/day or at the maximum tolerated dose. Any fixed dose combination of SGLT2 inhibitors and metformin was also allowed in this trial as background medication. A follow-up visit was scheduled one week after the end of treatment.0 / 2025 / 20287 / 202
PlaceboEligible subjects were given liraglutide placebo subcutaneously (s.c.), once daily (OD) for 26 weeks. Dose escalation for placebo matched that for liraglutide with regards to volume. Subjects remained on the stable dose of 1.8 mg placebo from week 3 to 26. Subjects continued their pre-trial SGLT2 inhibitor as monotherapy or in combination with metformin at stable pre-trial dose during the trial. Any one of three SGLT2 inhibitors were allowed as pre-trial therapy: Invokana®, Farxiga®/Forxiga® and Jardiance®. Stable pre-trial treatment with metformin was defined as ≥1500 mg/day or at the maximum tolerated dose. Any fixed dose combination of SGLT2 inhibitors and metformin was also allowed in this trial as background medication. A follow-up visit was scheduled one week after the end of treatment.0 / 1001 / 1008 / 100

Each cell reads participants affected / participants at risk, as the registry posted them.

Registry data comes from ClinicalTrials.gov. Study results come from studies, not from the registry. How PepBank works

Studies2

Studies that cite this trial.

Studies with results

2 studies on this page

Indexing hint: Randomized controlled trial · 2021

10 results

Efficacy of liraglutide added to sodium-glucose cotransporter-2 inhibitors in type 2 diabetes, stratified by baseline characteristics: Post-hoc analysis of LIRA-ADD2SGLT2i.

Blonde et al. 2021Diabetes, obesity & metabolismcited by 4

PMID 34132018PMC8518913DOI 10.1111/dom.14464PUB-34132018

Free to read · publisher termsCC BY-NC10 results
Read at sourceSee results (10)

Indexing hint: Randomized controlled trial · 2020

4 results

Liraglutide as add-on to sodium-glucose co-transporter-2 inhibitors in patients with inadequately controlled type 2 diabetes: LIRA-ADD2SGLT2i, a 26-week, randomized, double-blind, placebo-controlled trial.

Blonde et al. 2020Diabetes, obesity & metabolismcited by 44

PMID 31984646PMC7317838DOI 10.1111/dom.13978PUB-31984646

Free to read · publisher termsCC BY-NC4 results
Read at sourceSee results (4)

Eligibility

Who could join, as posted.

Sex
All
Age
from 18 Years
Healthy volunteers
Not accepted
Inclusion and exclusion criteria, as posted
Inclusion Criteria: * Informed consent obtained before any trial-related activities. Trial-related activities are any procedures that are carried out as part of the trial, including activities to determine suitability for the trial. * Male or female, age 18 years or older at the time of signing informed consent. * Diagnosed with type 2 diabetes mellitus. * HbA1c of 7.0-9.5% (53-80 mmol/mol) (both inclusive). * Stable dose of an SGLT-2 inhibitor as monotherapy or in combination (including fixed-dose drug combination) with a stable dose of metformin (1500 mg or more, or maximum tolerated dose) for at least 90 days prior to the day of screening. All medications in compliance with current local label. * Body mass index of 20 kg/m\^2 or above. Exclusion Criteria: * Female who is pregnant, breast-feeding or intends to become pregnant or is of child-bearing potential and not using an adequate contraceptive method (adequate contraceptive measure as required by local regulation or practice). * History of diabetic ketoacidosis while being treated with SGLT2 inhibitors. * Renal impairment measured as estimated Glomerular Filtration Rate (eGFR) value of less than 60 mL/min/1.73m\^2 as defined by Kidney Disease Improving Global Outcomes (KDIGO) classification using isotope dilution mass spectrometry (IDMS) for serum creatinine measured at screening. * Treatment with any medication for the indication of diabetes or obesity other than stated in the inclusion criteria within the past 90 days prior to the day of screening. However, short term insulin treatment for a maximum of 14 days during the 90 days prior to screening is allowed. * Family or personal history of multiple endocrine neoplasia type 2 or medullary thyroid carcinoma. Family is defined as a first degree relative. * History or presence of pancreatitis (acute or chronic). * Impaired liver function, defined as ALT 2.5 or more times upper normal limit at screening. * Subjects presently classified as being in New York Heart Association (NYHA) Class IV.

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