Clinical trial NCT02964247: LIRA-ADD2SGLT2i - Liraglutide Versus Placebo as add-on to SGLT2 Inhibitors.
Official title: LIRA-ADD2SGLT2i - Liraglutide Versus Placebo as add-on to SGLT2 Inhibitors
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Diabetes
Diabetes Mellitus, Type 2
Lead sponsor: Novo Nordisk A/S
Sponsor class: INDUSTRY
First posted: 2016-11-16
Enrollment: 303
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Change in HbA1c
timeFrame: Week 0, Week 26
Secondary outcomes:
measure: Change in Body Weight
timeFrame: Week 0, Week 26
measure: Change in Fasting Plasma Glucose
timeFrame: Week 0, Week 26
measure: Subjects Who Achieve HbA1c Below 7.0% (53 mmol/Mol), American Diabetes Association Target
timeFrame: Week 26
measure: Subjects Who Achieve HbA1c Below or Equal to 6.5% (48 mmol/Mol), American Association of Clinical Endocrinologists Target
timeFrame: Week 26
measure: Subjects Who Achieve HbA1c Below 7.0% (53 mmol/Mol) Without Severe or Blood Glucose Confirmed Symptomatic Hypoglycaemia Episodes and no Weight Gain.
timeFrame: Week 26
measure: Subjects Who Achieve HbA1c Reduction Above or Equal to 1% (11mmol/Mol) and Weight Loss Above or Equal to 3%.
timeFrame: Week 26
measure: Change in Self-measured Plasma Glucose 7-point Profile - Mean 7-point Profile
timeFrame: Week 0, Week 26
measure: Change in Self-measured Plasma Glucose 7-point Profile - Mean Post Prandial Increments (Over All Meals)
timeFrame: Week 0, Week 26
measure: Change in Body Mass Index (BMI)
timeFrame: Week 0, Week 26
measure: Subjects Who Achieve HbA1c Below 7.0% (53 mmol/Mol) and no Weight Gain
timeFrame: Week 26
measure: Subjects Who Achieve HbA1c Below 7.0% (53 mmol/Mol), no Weight Gain and Systolic Blood Pressure Below 140 mmHg.
timeFrame: Week 26
measure: Subjects Who Achieve HbA1c Reduction Above or Equal to 1% (11mmol/Mol)
timeFrame: Week 26
measure: Subjects Who Achieve HbA1c Reduction Above or Equal to 1% (11mmol/Mol) and no Weight Gain
timeFrame: Week 26
measure: Number of Treatment Emergent Adverse Events
timeFrame: Week 0 - 26 + 7 days
measure: Number of Treatment Emergent Severe or Blood Glucose Confirmed Symptomatic Hypoglycaemia Episodes
timeFrame: Week 0 - 26
measure: Change in Fasting Blood Lipids - Total Cholesterol
timeFrame: Week 0, Week 26
measure: Change in Fasting Blood Lipids - Low Density Lipoprotein (LDL) Cholesterol
timeFrame: Week 0, Week 26
measure: Change in Fasting Blood Lipids - High Density Lipoprotein (HDL) Cholesterol
timeFrame: Week 0, Week 26
measure: Change in Fasting Blood Lipids - Very Low Density Lipoprotein (VLDL) Cholesterol
timeFrame: Week 0, Week 26
measure: Change in Fasting Blood Lipids-triglycerides
timeFrame: Week 0, Week 26
measure: Change in Fasting Blood Lipids- Free Fatty Acids (FFA)
timeFrame: Week 0, Week 26
measure: Change in Waist Circumference
timeFrame: Week 0, Week 26
measure: Change in Systolic Blood Pressure
timeFrame: Week 0, Week 26
measure: Change in Diastolic Blood Pressure
timeFrame: Week 0, Week 26
measure: Subjects Who Achieve Weight Loss by 3% or More
timeFrame: Week 26
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Novo Nordisk Investigational Site
state: Alabama
city: Montgomery
country: United States
facility: Novo Nordisk Investigational Site
state: Alabama
city: Tucson
country: United States
facility: Novo Nordisk Investigational Site
state: Arizona
city: Lancaster
country: United States
facility: Novo Nordisk Investigational Site
state: California
city: Northridge
country: United States
facility: Novo Nordisk Investigational Site
state: California
city: Sacramento
country: United States
facility: Novo Nordisk Investigational Site
state: California
city: San Diego
country: United States
facility: Novo Nordisk Investigational Site
state: California
city: San Ramon
country: United States
facility: Novo Nordisk Investigational Site
state: California
city: Vista
country: United States
facility: Novo Nordisk Investigational Site
state: California
city: Gainesville
country: United States
facility: Novo Nordisk Investigational Site
state: Florida
city: Hollywood
country: United States
facility: Novo Nordisk Investigational Site
state: Florida
city: Jacksonville
country: United States
facility: Novo Nordisk Investigational Site
state: Florida
city: Jacksonville
country: United States
facility: Novo Nordisk Investigational Site
state: Florida
city: Jacksonville
country: United States
facility: Novo Nordisk Investigational Site
state: Florida
city: Maitland
country: United States
facility: Novo Nordisk Investigational Site
state: Florida
city: Miami Lakes
country: United States
facility: Novo Nordisk Investigational Site
state: Florida
city: Miami
country: United States
facility: Novo Nordisk Investigational Site
state: Florida
city: Miami
country: United States
facility: Novo Nordisk Investigational Site
state: Florida
city: Tampa
country: United States
facility: Novo Nordisk Investigational Site
state: Florida
city: Lawrenceville
country: United States
facility: Novo Nordisk Investigational Site
state: Georgia
city: Roswell
country: United States
facility: Novo Nordisk Investigational Site
state: Georgia
city: Statesboro
country: United States
facility: Novo Nordisk Investigational Site
state: Georgia
city: Blackfoot
country: United States
facility: Novo Nordisk Investigational Site
state: Idaho
city: Evansville
country: United States
facility: Novo Nordisk Investigational Site
state: Indiana
city: Topeka
country: United States
facility: Novo Nordisk Investigational Site
state: Kansas
city: Lexington
country: United States
facility: Novo Nordisk Investigational Site
state: Kentucky
city: New Orleans
country: United States
facility: Novo Nordisk Investigational Site
state: Louisiana
city: Kalamazoo
country: United States
facility: Novo Nordisk Investigational Site
state: Michigan
city: Rochester
country: United States
facility: Novo Nordisk Investigational Site
state: Michigan
city: Billings
country: United States
facility: Novo Nordisk Investigational Site
state: Montana
city: Henderson
country: United States
facility: Novo Nordisk Investigational Site
state: Nevada
city: Albany
country: United States
facility: Novo Nordisk Investigational Site
state: New York
city: West Seneca
country: United States
facility: Novo Nordisk Investigational Site
state: New York
city: Charlotte
country: United States
facility: Novo Nordisk Investigational Site
state: North Carolina
city: Charlotte
country: United States
facility: Novo Nordisk Investigational Site
state: North Carolina
city: Charlotte
country: United States
facility: Novo Nordisk Investigational Site
state: North Carolina
city: Kinston
country: United States
facility: Novo Nordisk Investigational Site
state: North Carolina
city: Wilmington
country: United States
facility: Novo Nordisk Investigational Site
state: North Carolina
city: Cincinnati
country: United States
facility: Novo Nordisk Investigational Site
state: Ohio
city: Columbus
country: United States
facility: Novo Nordisk Investigational Site
state: Ohio
city: McMurray
country: United States
facility: Novo Nordisk Investigational Site
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Novo Nordisk Investigational Site
state: Pennsylvania
city: Moncks Corner
country: United States
facility: Novo Nordisk Investigational Site
state: South Carolina
city: Mount Pleasant
country: United States
facility: Novo Nordisk Investigational Site
state: South Carolina
city: Myrtle Beach
country: United States
facility: Novo Nordisk Investigational Site
state: South Carolina
city: Spartanburg
country: United States
facility: Novo Nordisk Investigational Site
state: South Carolina
city: Memphis
country: United States
facility: Novo Nordisk Investigational Site
state: Tennessee
city: Nashville
country: United States
facility: Novo Nordisk Investigational Site
state: Tennessee
city: Dallas
country: United States
facility: Novo Nordisk Investigational Site
state: Texas
city: Edinburg
country: United States
facility: Novo Nordisk Investigational Site
state: Texas
city: Houston
country: United States
facility: Novo Nordisk Investigational Site
state: Texas
city: Houston
country: United States
facility: Novo Nordisk Investigational Site
state: Texas
city: Humble
country: United States
facility: Novo Nordisk Investigational Site
state: Texas
city: Round Rock
country: United States
facility: Novo Nordisk Investigational Site
state: Texas
city: Schertz
country: United States
facility: Novo Nordisk Investigational Site
state: Texas
city: Spokane
country: United States
facility: Novo Nordisk Investigational Site
state: Washington
city: Curitiba
country: Brazil
facility: Novo Nordisk Investigational Site
state: Parana
city: Porto Alegre
country: Brazil
facility: Novo Nordisk Investigational Site
state: Rio Grande Do Sul
city: São Paulo
country: Brazil
facility: Novo Nordisk Investigational Site
state: Sao Paulo
city: Ahmedabad
country: India
facility: Novo Nordisk Investigational Site
state: Gujarat
city: Bangalore
country: India
facility: Novo Nordisk Investigational Site
state: Karnataka
city: Indore
country: India
facility: Novo Nordisk Investigational Site
state: Madhya Pradesh
city: Pune
country: India
facility: Novo Nordisk Investigational Site
state: Maharashtra
city: Jaipur
country: India
facility: Novo Nordisk Investigational Site
state: Rajasthan
city: Coimbatore
country: India
facility: Novo Nordisk Investigational Site
state: Tamil Nadu
city: Hyderabad
country: India
facility: Novo Nordisk Investigational Site
state: Telengana
city: Kolkata
country: India
facility: Novo Nordisk Investigational Site
state: West Bengal
city: New Delhi
country: India
facility: Novo Nordisk Investigational Site
city: Haifa
country: Israel
facility: Novo Nordisk Investigational Site
city: Kfar Saba
country: Israel
facility: Novo Nordisk Investigational Site
city: Tel Hashomer
country: Israel
facility: Novo Nordisk Investigational Site
city: Tel-Aviv
country: Israel
facility: Novo Nordisk Investigational Site
city: Ponce
country: Puerto Rico
facility: Novo Nordisk Investigational Site
city: Saint-Petersburg
country: Russian Federation
facility: Novo Nordisk Investigational Site
city: Saint-Petersburg
country: Russian Federation
facility: Novo Nordisk Investigational Site
city: Saint-Petersburg
country: Russian Federation
facility: Novo Nordisk Investigational Site
city: Saint-Petersburg
country: Russian Federation
facility: Novo Nordisk Investigational Site
city: St. Petersburg
country: Russian Federation
facility: Novo Nordisk Investigational Site
city: Al Ain
country: United Arab Emirates
facility: Novo Nordisk Investigational Site
city: Dubai
country: United Arab Emirates
facility: Novo Nordisk Investigational Site
city: Umm Al Quwain
country: United Arab Emirates
facility: Novo Nordisk Investigational Site
city: Umm Al Quwain
country: United Arab Emirates
facility: Novo Nordisk Investigational Site
Study officials:
References:
citation: Blonde L, Belousova L, Fainberg U, Garcia-Hernandez PA, Jain SM, Kaltoft MS, Mosenzon O, Nafach J, Palle MS, Rea R. 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. Diabetes Obes Metab. 2020 Jun;22(6):929-937. doi: 10.1111/dom.13978. Epub 2020 Feb 14.
citation: Blonde L, Fainberg U, Kaltoft MS, Mosenzon O, Ramesh C, Rea R. Efficacy of liraglutide added to sodium-glucose cotransporter-2 inhibitors in type 2 diabetes, stratified by baseline characteristics: Post-hoc analysis of LIRA-ADD2SGLT2i. Diabetes Obes Metab. 2021 Oct;23(10):2234-2241. doi: 10.1111/dom.14464. Epub 2021 Jul 8.