Efficacy and Safety of Switching From Sitagliptin to Liraglutide in Subjects With Type 2 Diabetes Not Achieving Adequate Glycaemic Control on Sitagliptin and Metformin

Diabetes Mellitus, Type 2 Clinical Trial

— LIRA-SWITCH™  

Official title:

Efficacy and Safety of Switching From Sitagliptin to Liraglutide in Subjects With Type 2 Diabetes Not Achieving Adequate Glycaemic Control on Sitagliptin and Metformin

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01907854
• Other study ID #: NN2211-4059
• Secondary ID: 2012-004931-22U1
• Status: Completed
• Phase: Phase 4
• Start date: December 2, 2013
• Est. completion date: June 15, 2015

Study information

• Verified date: September 2018
• Source: Novo Nordisk A/S
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This trial is conducted in Asia, Europe and North America. The aim of the trial is to investigate the efficacy and safety of switching from sitagliptin to liraglutide in subjects with type 2 diabetes not achieving adequate glycaemic control on sitagliptin and metformin.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 407
• Est. completion date: June 15, 2015
• Est. primary completion date: June 15, 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

• - Subjects diagnosed with type 2 diabetes and treated with metformin equal to or above 1500 mg/day (or maximum tolerated dose equal to or above 1000 mg/day) and sitagliptin 100 mg/day, both at a stable dose for at least 90 days prior to screening. Stable is defined as unchanged medication and dose

• - HbA1c 7.5% - 9.5% (58 mmol/mol - 80 mmol/mol) (both inclusive)

• - Body mass index equal to or above 20 kg/m^2

Exclusion Criteria:

• - Any chronic disorder or severe disease which at the discretion of the investigator might jeopardise subject's safety or compliance with the protocol

• - Treatment with glucose lowering agent(s) other than stated in the inclusion criteria in a period of 90 days prior to screening. An exception is short-term treatment (equal to or less than 7 days in total) with insulin in connection with intercurrent illness

• - Female who is pregnant, breast-feeding, intends to become pregnant or of child-bearing potential not using adequate contraceptive methods (adequate contraceptive measures as required by local regulations or practice)

• - History of chronic pancreatitis or idiopathic acute pancreatitis

• - Screening calcitonin value equal to or above 50 ng/L

• - Personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia syndrome type 2

• - Diagnosis of malignant neoplasm in the previous 5 years (except basal cell skin cancer or squamous cell skin cancer)

• - Impaired liver function, defined as alanine aminotransferase equal to or above 2.5 times upper normal limit

• - Impaired renal function defined as estimated glomerular filtration rate 60 mL/min/1.73 m^2 per modification of diet in renal disease formula

• - Any episode of unstable angina, acute coronary event, cerebral stroke/transient ischemic attack or other significant cardiovascular event as judged by the investigator within 90 days prior to screening

• - Heart failure, New York Heart Association class IV

• - Uncontrolled treated or untreated hypertension (systolic blood pressure equal to or above 180 mmHg and/or diastolic blood pressure equal to or above 100 mmHg)

Related Conditions & MeSH terms

• Diabetes
• Diabetes Mellitus
• Diabetes Mellitus, Type 2

Intervention

Drug:
• liraglutide
Starting dose of 0.6 mg/day, with weekly dose escalations of 0.6 mg/day until the maintenance dose of 1.8 mg/day is reached. Administered subcutaneously (s.c., under the skin) once daily + metformin tablets (at least 1000 mg/day)
• sitagliptin
100 mg/day sitagliptin tablets once-daily + metformin (at least 1000 mg/day)
• placebo
Sitagliptin placebo tablets once-daily
• placebo
Sitagliptin placebo tablets once-daily

Locations

Country	Name	City	State
Canada	Novo Nordisk Investigational Site	Brampton	Ontario
Canada	Novo Nordisk Investigational Site	Burlington	Ontario
Canada	Novo Nordisk Investigational Site	Concord	Ontario
Canada	Novo Nordisk Investigational Site	Drummondville	Quebec
Canada	Novo Nordisk Investigational Site	Etobicoke	Ontario
Canada	Novo Nordisk Investigational Site	Grimsby	Ontario
Canada	Novo Nordisk Investigational Site	Montreal	Quebec
Canada	Novo Nordisk Investigational Site	Ottawa	Ontario
Canada	Novo Nordisk Investigational Site	Quebec
Canada	Novo Nordisk Investigational Site	Sarnia	Ontario
Canada	Novo Nordisk Investigational Site	St. Romuald	Quebec
Canada	Novo Nordisk Investigational Site	Strathroy	Ontario
Canada	Novo Nordisk Investigational Site	Surrey	British Columbia
Canada	Novo Nordisk Investigational Site	Toronto	Ontario
Canada	Novo Nordisk Investigational Site	Toronto	Ontario
Canada	Novo Nordisk Investigational Site	Toronto	Ontario
Canada	Novo Nordisk Investigational Site	Trois Rivières	Quebec
Hungary	Novo Nordisk Investigational Site	Budapest
Hungary	Novo Nordisk Investigational Site	Debrecen
Hungary	Novo Nordisk Investigational Site	Eger
Hungary	Novo Nordisk Investigational Site	Gyula
Hungary	Novo Nordisk Investigational Site	Salgótarján
Hungary	Novo Nordisk Investigational Site	Sopron
Hungary	Novo Nordisk Investigational Site	Szeged
Hungary	Novo Nordisk Investigational Site	Tatabánya
India	Novo Nordisk Investigational Site	Ahmedabad	Gujarat
India	Novo Nordisk Investigational Site	Bangalore	Karnataka
India	Novo Nordisk Investigational Site	Gandhinagar	Gujarat
India	Novo Nordisk Investigational Site	Hyderabad	Andhra Pradesh
India	Novo Nordisk Investigational Site	Mumbai	Maharashtra
India	Novo Nordisk Investigational Site	New Delhi
India	Novo Nordisk Investigational Site	Pune	Maharashtra
India	Novo Nordisk Investigational Site	Visakhapatnam	Andhra Pradesh
Israel	Novo Nordisk Investigational Site	Haifa
Israel	Novo Nordisk Investigational Site	Haifa
Israel	Novo Nordisk Investigational Site	Herzliya
Israel	Novo Nordisk Investigational Site	Kfar Saba
Israel	Novo Nordisk Investigational Site	Nahariya
Israel	Novo Nordisk Investigational Site	Ofakim
Israel	Novo Nordisk Investigational Site	Tel Aviv
Israel	Novo Nordisk Investigational Site	Tel-Aviv
Puerto Rico	Novo Nordisk Investigational Site	San Juan
Spain	Novo Nordisk Investigational Site	Badalona
Spain	Novo Nordisk Investigational Site	El Ferrol
Spain	Novo Nordisk Investigational Site	Granada
Spain	Novo Nordisk Investigational Site	Málaga
Spain	Novo Nordisk Investigational Site	Sanlúcar de Barrameda
Spain	Novo Nordisk Investigational Site	Sevilla
United States	Novo Nordisk Investigational Site	Akron	Ohio
United States	Novo Nordisk Investigational Site	Albany	New York
United States	Novo Nordisk Investigational Site	Arlington Heights	Illinois
United States	Novo Nordisk Investigational Site	Avon	Indiana
United States	Novo Nordisk Investigational Site	Bangor	Maine
United States	Novo Nordisk Investigational Site	Berlin	New Jersey
United States	Novo Nordisk Investigational Site	Blackfoot	Idaho
United States	Novo Nordisk Investigational Site	Charlotte	North Carolina
United States	Novo Nordisk Investigational Site	Chicago	Illinois
United States	Novo Nordisk Investigational Site	Chiefland	Florida
United States	Novo Nordisk Investigational Site	Colorado Springs	Colorado
United States	Novo Nordisk Investigational Site	Colorado Springs	Colorado
United States	Novo Nordisk Investigational Site	Council Bluffs	Iowa
United States	Novo Nordisk Investigational Site	Edinburg	Texas
United States	Novo Nordisk Investigational Site	Elizabeth	New Jersey
United States	Novo Nordisk Investigational Site	Escondido	California
United States	Novo Nordisk Investigational Site	Evansville	Indiana
United States	Novo Nordisk Investigational Site	Evansville	Indiana
United States	Novo Nordisk Investigational Site	Fall River	Massachusetts
United States	Novo Nordisk Investigational Site	Fort Lauderdale	Florida
United States	Novo Nordisk Investigational Site	Fort Worth	Texas
United States	Novo Nordisk Investigational Site	Hialeah	Florida
United States	Novo Nordisk Investigational Site	Honolulu	Hawaii
United States	Novo Nordisk Investigational Site	Houston	Texas
United States	Novo Nordisk Investigational Site	Houston	Texas
United States	Novo Nordisk Investigational Site	Houston	Texas
United States	Novo Nordisk Investigational Site	Houston	Texas
United States	Novo Nordisk Investigational Site	Jacksonville	Florida
United States	Novo Nordisk Investigational Site	Jacksonville	Florida
United States	Novo Nordisk Investigational Site	Jacksonville	Florida
United States	Novo Nordisk Investigational Site	Johns Creek	Georgia
United States	Novo Nordisk Investigational Site	Las Vegas	Nevada
United States	Novo Nordisk Investigational Site	Memphis	Tennessee
United States	Novo Nordisk Investigational Site	Miami	Florida
United States	Novo Nordisk Investigational Site	Midland	Texas
United States	Novo Nordisk Investigational Site	Mission Viejo	California
United States	Novo Nordisk Investigational Site	Moncks Corner	South Carolina
United States	Novo Nordisk Investigational Site	Nashua	New Hampshire
United States	Novo Nordisk Investigational Site	New Braunfels	Texas
United States	Novo Nordisk Investigational Site	North Miami	Florida
United States	Novo Nordisk Investigational Site	North Richland Hills	Texas
United States	Novo Nordisk Investigational Site	Orangeburg	South Carolina
United States	Novo Nordisk Investigational Site	Peoria	Illinois
United States	Novo Nordisk Investigational Site	Phoenix	Arizona
United States	Novo Nordisk Investigational Site	Phoenix	Arizona
United States	Novo Nordisk Investigational Site	Port Charlotte	Florida
United States	Novo Nordisk Investigational Site	Reading	Pennsylvania
United States	Novo Nordisk Investigational Site	Roseville	California
United States	Novo Nordisk Investigational Site	Saint Peters	Missouri
United States	Novo Nordisk Investigational Site	Salisbury	North Carolina
United States	Novo Nordisk Investigational Site	San Antonio	Texas
United States	Novo Nordisk Investigational Site	Skokie	Illinois
United States	Novo Nordisk Investigational Site	Spokane	Washington
United States	Novo Nordisk Investigational Site	Sugar Land	Texas
United States	Novo Nordisk Investigational Site	Troy	Michigan
United States	Novo Nordisk Investigational Site	Tucson	Arizona
United States	Novo Nordisk Investigational Site	Tucson	Arizona
United States	Novo Nordisk Investigational Site	Virginia Beach	Virginia

Sponsors (1)

Lead Sponsor	Collaborator
Novo Nordisk A/S

Countries where clinical trial is conducted

United States,  Canada,  Hungary,  India,  Israel,  Puerto Rico,  Spain, 

References & Publications (1)

Bailey TS, Takács R, Tinahones FJ, Rao PV, Tsoukas GM, Thomsen AB, Kaltoft MS, Maislos M. Efficacy and safety of switching from sitagliptin to liraglutide in subjects with type 2 diabetes (LIRA-SWITCH): a randomized, double-blind, double-dummy, active-con — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in HbA1c (Glycosylated Haemoglobin)	Change from baseline in HbA1c was analysed after 26 weeks of treatment. Analysis population set: full analysis set (FAS); all randomised subjects receiving at least one dose of any of the trial products. Missing values were imputed using mixed model for repeated measurements (MMRM).	From baseline to week 26
Secondary	Change in Body Weight	Change from baseline in body weight was analysed after 26 weeks of treatment. Analysis population set: FAS: all randomised subjects receiving at least one dose of any of the trial products. Missing values were imputed using MMRM.	From baseline to week 26
Secondary	Change in Fasting Plasma Glucose	Change from baseline in fasting plasma glucose was analysed after 26 weeks of treatment. Missing values were imputed using MMRM.	From baseline to week 26
Secondary	Change in Fasting Blood Lipids	Ratio to baseline in fasting blood lipids (total cholesterol, low density lipoprotein [LDL], very low density lipoprotein [VLDL], high density lipoprotein [HDL], triglycerides, and free fatty acids) were analysed after 26 weeks treatment. Missing values were imputed using MMRM. Here we are presenting ratio to baseline data.	From baseline to week 26
Secondary	Change in Systolic Blood Pressure and Diastolic Blood Pressure	Change from baseline in systolic and diastolic blood pressure were analysed after 26 weeks of treatment. Missing values were imputed using MMRM.	From baseline to week 26
Secondary	Subjects Who Achieve HbA1c Below 7.0% (53 mmol/Mol) (American Diabetes Association Target) (y/n)	Number of subjects who achieve HbA1c <7.0% were analysed after 26 weeks of treatment. Missing values were imputed using MMRM.	After 26 weeks of treatment
Secondary	Number of Treatment Emergent Adverse Events (TEAEs)	A treatment emergent adverse event (TEAE) was defined as an event that had an onset date (or increase in severity) on or after the first day of exposure to randomised treatment and no later than seven days after the last day of randomised treatment. The number of TEAEs was recorded during 26 weeks of treatment plus one week follow-up period.	During 26 weeks of treatment plus one week follow-up period.

External Links

•   Clinical Trials at Novo Nordisk