Efficacy and Safety of Switching From Sitagliptin to Liraglutide in Subjects With Type 2 Diabetes Not Achieving Adequate Glycaemic Control on Sitagliptin and Metformin (LIRA-SWITCH™)

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.

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus, Type 2; Diabetes
• Intervention / Treatment: Drug: liraglutide; Drug: placebo; Drug: sitagliptin

• Study Type: Interventional
• Enrollment (Actual): 407
• Phase: Phase 4

Contacts and Locations

Study Locations

• Canada
  • Quebec, Canada, G3K 2P8
    • Novo Nordisk Investigational Site
  • British Columbia
    • Surrey, British Columbia, Canada, V3S 2N6
      • Novo Nordisk Investigational Site
  • Ontario
    • Brampton, Ontario, Canada, L6S 0C6
      • Novo Nordisk Investigational Site
    • Burlington, Ontario, Canada, L7M 4Y1
      • Novo Nordisk Investigational Site
    • Concord, Ontario, Canada, L4K 4M2
      • Novo Nordisk Investigational Site
    • Etobicoke, Ontario, Canada, M9R 4E1
      • Novo Nordisk Investigational Site
    • Grimsby, Ontario, Canada, L3M 1P3
      • Novo Nordisk Investigational Site
    • Ottawa, Ontario, Canada, K1K 4L2
      • Novo Nordisk Investigational Site
    • Sarnia, Ontario, Canada, N7T 4X3
      • Novo Nordisk Investigational Site
    • Strathroy, Ontario, Canada, N7G 1Y7
      • Novo Nordisk Investigational Site
    • Toronto, Ontario, Canada, M3J 1N2
      • Novo Nordisk Investigational Site
    • Toronto, Ontario, Canada, M4G 3E8
      • Novo Nordisk Investigational Site
    • Toronto, Ontario, Canada, M9V 4B4
      • Novo Nordisk Investigational Site
  • Quebec
    • Drummondville, Quebec, Canada, J2B 7T1
      • Novo Nordisk Investigational Site
    • Montreal, Quebec, Canada, H4A 3T2
      • Novo Nordisk Investigational Site
    • St. Romuald, Quebec, Canada, G6W 5M6
      • Novo Nordisk Investigational Site
    • Trois Rivières, Quebec, Canada, G8T 7A1
      • Novo Nordisk Investigational Site
• Hungary
  • Budapest, Hungary, 1042
    • Novo Nordisk Investigational Site
  • Debrecen, Hungary, 4043
    • Novo Nordisk Investigational Site
  • Eger, Hungary, 3300
    • Novo Nordisk Investigational Site
  • Gyula, Hungary, H-5700
    • Novo Nordisk Investigational Site
  • Salgótarján, Hungary, 3100
    • Novo Nordisk Investigational Site
  • Sopron, Hungary, 9400
    • Novo Nordisk Investigational Site
  • Szeged, Hungary, H-6720
    • Novo Nordisk Investigational Site
  • Tatabánya, Hungary, 2800
    • Novo Nordisk Investigational Site
• India
  • New Delhi, India, 110060
    • Novo Nordisk Investigational Site
  • Andhra Pradesh
    • Hyderabad, Andhra Pradesh, India, 500082
      • Novo Nordisk Investigational Site
    • Visakhapatnam, Andhra Pradesh, India, 530002
      • Novo Nordisk Investigational Site
  • Gujarat
    • Ahmedabad, Gujarat, India, 380008
      • Novo Nordisk Investigational Site
    • Gandhinagar, Gujarat, India, 382428
      • Novo Nordisk Investigational Site
  • Karnataka
    • Bangalore, Karnataka, India, 560002
      • Novo Nordisk Investigational Site
  • Maharashtra
    • Mumbai, Maharashtra, India, 400007
      • Novo Nordisk Investigational Site
    • Pune, Maharashtra, India, 411040
      • Novo Nordisk Investigational Site
• Israel
  • Haifa, Israel, 35152
    • Novo Nordisk Investigational Site
  • Haifa, Israel, 3339419
    • Novo Nordisk Investigational Site
  • Herzliya, Israel, 46851
    • Novo Nordisk Investigational Site
  • Kfar Saba, Israel, 44281
    • Novo Nordisk Investigational Site
  • Nahariya, Israel, 22100
    • Novo Nordisk Investigational Site
  • Ofakim, Israel, 87520
    • Novo Nordisk Investigational Site
  • Tel Aviv, Israel, 6937947
    • Novo Nordisk Investigational Site
  • Tel-Aviv, Israel, 62038
    • Novo Nordisk Investigational Site
• Puerto Rico
  • San Juan, Puerto Rico, 00921
    • Novo Nordisk Investigational Site
• Spain
  • Badalona, Spain, 08916
    • Novo Nordisk Investigational Site
  • El Ferrol, Spain, 15405
    • Novo Nordisk Investigational Site
  • Granada, Spain, 18003
    • Novo Nordisk Investigational Site
  • Málaga, Spain, 29006
    • Novo Nordisk Investigational Site
  • Sanlúcar de Barrameda, Spain, 11540
    • Novo Nordisk Investigational Site
  • Sevilla, Spain, 41009
    • Novo Nordisk Investigational Site
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85027
      • Novo Nordisk Investigational Site
    • Phoenix, Arizona, United States, 85018
      • Novo Nordisk Investigational Site
    • Tucson, Arizona, United States, 85724
      • Novo Nordisk Investigational Site
    • Tucson, Arizona, United States, 85704
      • Novo Nordisk Investigational Site
  • California
    • Escondido, California, United States, 92025
      • Novo Nordisk Investigational Site
    • Mission Viejo, California, United States, 92691
      • Novo Nordisk Investigational Site
    • Roseville, California, United States, 95661
      • Novo Nordisk Investigational Site
  • Colorado
    • Colorado Springs, Colorado, United States, 80909
      • Novo Nordisk Investigational Site
    • Colorado Springs, Colorado, United States, 80922
      • Novo Nordisk Investigational Site
  • Florida
    • Chiefland, Florida, United States, 32626
      • Novo Nordisk Investigational Site
    • Fort Lauderdale, Florida, United States, 33308
      • Novo Nordisk Investigational Site
    • Hialeah, Florida, United States, 33012
      • Novo Nordisk Investigational Site
    • Jacksonville, Florida, United States, 32216
      • Novo Nordisk Investigational Site
    • Jacksonville, Florida, United States, 32207
      • Novo Nordisk Investigational Site
    • Jacksonville, Florida, United States, 32258
      • Novo Nordisk Investigational Site
    • Miami, Florida, United States, 33183
      • Novo Nordisk Investigational Site
    • North Miami, Florida, United States, 33181
      • Novo Nordisk Investigational Site
    • Port Charlotte, Florida, United States, 33952
      • Novo Nordisk Investigational Site
  • Georgia
    • Johns Creek, Georgia, United States, 30097
      • Novo Nordisk Investigational Site
  • Hawaii
    • Honolulu, Hawaii, United States, 96814
      • Novo Nordisk Investigational Site
  • Idaho
    • Blackfoot, Idaho, United States, 83221
      • Novo Nordisk Investigational Site
  • Illinois
    • Arlington Heights, Illinois, United States, 60005-4144
      • Novo Nordisk Investigational Site
    • Chicago, Illinois, United States, 60604
      • Novo Nordisk Investigational Site
    • Peoria, Illinois, United States, 61602
      • Novo Nordisk Investigational Site
    • Skokie, Illinois, United States, 60077
      • Novo Nordisk Investigational Site
  • Indiana
    • Avon, Indiana, United States, 46123
      • Novo Nordisk Investigational Site
    • Evansville, Indiana, United States, 47714
      • Novo Nordisk Investigational Site
    • Evansville, Indiana, United States, 47725
      • Novo Nordisk Investigational Site
  • Iowa
    • Council Bluffs, Iowa, United States, 51501
      • Novo Nordisk Investigational Site
  • Maine
    • Bangor, Maine, United States, 04401
      • Novo Nordisk Investigational Site
  • Massachusetts
    • Fall River, Massachusetts, United States, 02720
      • Novo Nordisk Investigational Site
  • Michigan
    • Troy, Michigan, United States, 48085-5524
      • Novo Nordisk Investigational Site
  • Missouri
    • Saint Peters, Missouri, United States, 63376
      • Novo Nordisk Investigational Site
  • Nevada
    • Las Vegas, Nevada, United States, 89119
      • Novo Nordisk Investigational Site
  • New Hampshire
    • Nashua, New Hampshire, United States, 03063
      • Novo Nordisk Investigational Site
  • New Jersey
    • Berlin, New Jersey, United States, 08009
      • Novo Nordisk Investigational Site
    • Elizabeth, New Jersey, United States, 07202
      • Novo Nordisk Investigational Site
  • New York
    • Albany, New York, United States, 12206
      • Novo Nordisk Investigational Site
  • North Carolina
    • Charlotte, North Carolina, United States, 28210
      • Novo Nordisk Investigational Site
    • Salisbury, North Carolina, United States, 28144
      • Novo Nordisk Investigational Site
  • Ohio
    • Akron, Ohio, United States, 44311
      • Novo Nordisk Investigational Site
  • Pennsylvania
    • Reading, Pennsylvania, United States, 19606
      • Novo Nordisk Investigational Site
  • South Carolina
    • Moncks Corner, South Carolina, United States, 29461
      • Novo Nordisk Investigational Site
    • Orangeburg, South Carolina, United States, 29118
      • Novo Nordisk Investigational Site
  • Tennessee
    • Memphis, Tennessee, United States, 38119
      • Novo Nordisk Investigational Site
  • Texas
    • Edinburg, Texas, United States, 78539
      • Novo Nordisk Investigational Site
    • Fort Worth, Texas, United States, 76104
      • Novo Nordisk Investigational Site
    • Houston, Texas, United States, 77024
      • Novo Nordisk Investigational Site
    • Houston, Texas, United States, 77030
      • Novo Nordisk Investigational Site
    • Houston, Texas, United States, 77079
      • Novo Nordisk Investigational Site
    • Houston, Texas, United States, 77036
      • Novo Nordisk Investigational Site
    • Midland, Texas, United States, 79707
      • Novo Nordisk Investigational Site
    • New Braunfels, Texas, United States, 78130
      • Novo Nordisk Investigational Site
    • North Richland Hills, Texas, United States, 76180
      • Novo Nordisk Investigational Site
    • San Antonio, Texas, United States, 78245
      • Novo Nordisk Investigational Site
    • Sugar Land, Texas, United States, 77478
      • Novo Nordisk Investigational Site
  • Virginia
    • Virginia Beach, Virginia, United States, 23454
      • Novo Nordisk Investigational Site
  • Washington
    • Spokane, Washington, United States, 99202-3649
      • Novo Nordisk Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Liraglutide + metformin + sitagliptin placebo	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); Drug: placebo; Sitagliptin placebo tablets once-daily
Experimental: Sitagliptin + metformin + liraglutide placebo	Drug: placebo; Sitagliptin placebo tablets once-daily; Drug: sitagliptin; 100 mg/day sitagliptin tablets once-daily + metformin (at least 1000 mg/day)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
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
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
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
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
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.

Collaborators and Investigators

• Sponsor: Novo Nordisk A/S

Publications and helpful links

General Publications

• Bailey TS, Takacs 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-controlled 26-week trial. Diabetes Obes Metab. 2016 Dec;18(12):1191-1198. doi: 10.1111/dom.12736. Epub 2016 Sep 14.

Helpful Links

• Clinical Trials at Novo Nordisk

Study record dates

Study Major Dates

• Study Start (Actual): December 2, 2013
• Primary Completion (Actual): June 15, 2015
• Study Completion (Actual): June 15, 2015

Study Registration Dates

• First Submitted: July 22, 2013
• First Submitted That Met QC Criteria: July 22, 2013
• First Posted (Estimate): July 25, 2013

Study Record Updates

• Last Update Posted (Actual): October 2, 2018
• Last Update Submitted That Met QC Criteria: September 3, 2018
• Last Verified: September 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Protease Inhibitors; Incretins; Dipeptidyl-Peptidase IV Inhibitors; Liraglutide; Sitagliptin Phosphate
• Other Study ID Numbers: NN2211-4059; 2012-004931-22 (EudraCT Number); U1111-1136-2073 (Other Identifier: WHO); CTRI/2014/05/004623 (Registry Identifier: Clinical Trial Registry India (CTRI))