Dose-finding of Semaglutide Administered Subcutaneously Once Daily Versus Placebo and Liraglutide in Subjects With Type 2 Diabetes

This trial is conducted globally. The aim of this trial is to investigate dose-finding of semaglutide administered subcutaneously once daily versus placebo and liraglutide in subjects with type 2 diabetes

Study Overview

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

• Study Type: Interventional
• Enrollment (Actual): 706
• Phase: Phase 2

Contacts and Locations

Study Locations

• Austria
  • Graz, Austria, 8010
    • Novo Nordisk Investigational Site
  • Saint Stefan, Austria, 8511
    • Novo Nordisk Investigational Site
  • Wien, Austria, 1130
    • Novo Nordisk Investigational Site
• Canada
  • British Columbia
    • Coquitlam, British Columbia, Canada, V3K 3P4
      • Novo Nordisk Investigational Site
  • New Brunswick
    • Moncton, New Brunswick, Canada, E1G 1A7
      • Novo Nordisk Investigational Site
  • Ontario
    • Hamilton, Ontario, Canada, L8M 1K7
      • Novo Nordisk Investigational Site
    • Hamilton, Ontario, Canada, L8K 3P3
      • Novo Nordisk Investigational Site
    • Sarnia, Ontario, Canada, N7T 4X3
      • Novo Nordisk Investigational Site
    • Strathroy, Ontario, Canada, N7G 1Y7
      • Novo Nordisk Investigational Site
  • Quebec
    • Laval, Quebec, Canada, H7T 2P5
      • Novo Nordisk Investigational Site
    • Pointe Claire, Quebec, Canada, H9R 4S3
      • Novo Nordisk Investigational Site
• Czechia
  • Benesov, Czechia, 25601
    • Novo Nordisk Investigational Site
  • Brno, Czechia, 602 00
    • Novo Nordisk Investigational Site
  • Liberec, Czechia, 46001
    • Novo Nordisk Investigational Site
  • Nachod, Czechia, 54701
    • Novo Nordisk Investigational Site
  • Plzeň, Czechia, 301 00
    • Novo Nordisk Investigational Site
  • Police nad Metuji, Czechia, 54954
    • Novo Nordisk Investigational Site
  • Praha 4, Czechia, 140 46
    • Novo Nordisk Investigational Site
  • Praha 5, Czechia, 150 00
    • Novo Nordisk Investigational Site
  • Trutnov, Czechia, 541 01
    • Novo Nordisk Investigational Site
• Germany
  • Eisenach, Germany, 99817
    • Novo Nordisk Investigational Site
  • Friedrichsthal, Germany, 66299
    • Novo Nordisk Investigational Site
  • Hamburg, Germany, 22607
    • Novo Nordisk Investigational Site
  • Münster, Germany, 48145
    • Novo Nordisk Investigational Site
  • Pohlheim, Germany, 35415
    • Novo Nordisk Investigational Site
  • Rehlingen-Siersburg, Germany, 66780
    • Novo Nordisk Investigational Site
  • Saint Ingbert-Oberwürzbach, Germany, 66386
    • Novo Nordisk Investigational Site
  • Stuttgart, Germany, 70378
    • Novo Nordisk Investigational Site
  • Sulzbach-Rosenberg, Germany, 92237
    • Novo Nordisk Investigational Site
• Malaysia
  • Klang, Selangor, Malaysia, 41200
    • Novo Nordisk Investigational Site
  • Kota Bharu, Malaysia, 15586
    • Novo Nordisk Investigational Site
  • Penang, Malaysia, 10450
    • Novo Nordisk Investigational Site
  • Seremban, Malaysia, 70300
    • Novo Nordisk Investigational Site
  • Seri Manjung, Malaysia, 32040
    • Novo Nordisk Investigational Site
• Russian Federation
  • Dzerzhinskiy, Russian Federation, 140091
    • Novo Nordisk Investigational Site
  • Kazan, Russian Federation, 420073
    • Novo Nordisk Investigational Site
  • Saint-Petersburg, Russian Federation, 191119
    • Novo Nordisk Investigational Site
  • Saratov, Russian Federation, 410039
    • Novo Nordisk Investigational Site
  • Saratov, Russian Federation, 410031
    • Novo Nordisk Investigational Site
  • Smolensk, Russian Federation, 214031
    • Novo Nordisk Investigational Site
  • Syktyvkar, Russian Federation, 167981
    • Novo Nordisk Investigational Site
  • Voronezh, Russian Federation, 394018
    • Novo Nordisk Investigational Site
• Serbia
  • Belgrade, Serbia, 11000
    • Novo Nordisk Investigational Site
  • Kragujevac, Serbia, 34000
    • Novo Nordisk Investigational Site
  • Nis, Serbia, 18000
    • Novo Nordisk Investigational Site
  • Novi Sad, Serbia, 21000
    • Novo Nordisk Investigational Site
  • Zajecar, Serbia, 19000
    • Novo Nordisk Investigational Site
• South Africa
  • Free State
    • Bloemfontein, Free State, South Africa, 9301
      • Novo Nordisk Investigational Site
  • Gauteng
    • Johannesburg, Gauteng, South Africa, 1812
      • Novo Nordisk Investigational Site
    • Midrand, Gauteng, South Africa, 1685
      • Novo Nordisk Investigational Site
  • KwaZulu-Natal
    • Durban, KwaZulu-Natal, South Africa, 4092
      • Novo Nordisk Investigational Site
    • Durban, KwaZulu-Natal, South Africa, 4450
      • Novo Nordisk Investigational Site
  • Mpumalanga
    • Middleburg, Mpumalanga, South Africa, 1055
      • Novo Nordisk Investigational Site
• United Kingdom
  • Basingstoke, United Kingdom, RG24 9GT
    • Novo Nordisk Investigational Site
  • Belfast, United Kingdom, BT16 1RH
    • Novo Nordisk Investigational Site
  • Bexhill-on-Sea, United Kingdom, TN39 4SP
    • Novo Nordisk Investigational Site
  • Blackburn, United Kingdom, BB2 1AX
    • Novo Nordisk Investigational Site
  • Bristol, United Kingdom, BS10 5NB
    • Novo Nordisk Investigational Site
  • Chesterfield, Derbyshire, United Kingdom, S40 4AA
    • Novo Nordisk Investigational Site
  • Devon, United Kingdom, EX2 5DW
    • Novo Nordisk Investigational Site
  • Harrogate, North Yorkshire, United Kingdom, HG2 7SX
    • Novo Nordisk Investigational Site
  • Hinckley, United Kingdom, LE10 2SE
    • Novo Nordisk Investigational Site
  • Oxford, United Kingdom, OX3 7LE
    • Novo Nordisk Investigational Site
  • Plymouth, United Kingdom, PL8 8DQ
    • Novo Nordisk Investigational Site
  • Sidcup, United Kingdom, DA14 6LT
    • Novo Nordisk Investigational Site
  • Truro, United Kingdom, TR1 3LJ
    • Novo Nordisk Investigational Site
• United States
  • Alabama
    • Birmingham, Alabama, United States, 35294
      • Novo Nordisk Investigational Site
    • Birmingham, Alabama, United States, 35209
      • Novo Nordisk Investigational Site
  • California
    • Coronado, California, United States, 92118
      • Novo Nordisk Investigational Site
    • Lancaster, California, United States, 93534
      • Novo Nordisk Investigational Site
    • Riverside, California, United States, 92506
      • Novo Nordisk Investigational Site
    • Tustin, California, United States, 92780
      • Novo Nordisk Investigational Site
    • Van Nuys, California, United States, 91405
      • Novo Nordisk Investigational Site
    • Vista, California, United States, 92083
      • Novo Nordisk Investigational Site
    • Walnut Creek, California, United States, 94598
      • Novo Nordisk Investigational Site
  • Connecticut
    • Hartford, Connecticut, United States, 06105
      • Novo Nordisk Investigational Site
  • Florida
    • Boca Raton, Florida, United States, 33433
      • Novo Nordisk Investigational Site
    • Gainesville, Florida, United States, 32653
      • Novo Nordisk Investigational Site
    • Gainesville, Florida, United States, 32609
      • Novo Nordisk Investigational Site
    • Hialeah, Florida, United States, 33012
      • Novo Nordisk Investigational Site
    • Miami, Florida, United States, 33173
      • Novo Nordisk Investigational Site
    • Miami, Florida, United States, 33183
      • Novo Nordisk Investigational Site
    • Pembroke Pines, Florida, United States, 33026
      • Novo Nordisk Investigational Site
    • Ponte Vedra, Florida, United States, 32081
      • Novo Nordisk Investigational Site
  • Georgia
    • Atlanta, Georgia, United States, 30342
      • Novo Nordisk Investigational Site
    • Marietta, Georgia, United States, 30067
      • Novo Nordisk Investigational Site
  • Illinois
    • Evanston, Illinois, United States, 60201-2477
      • Novo Nordisk Investigational Site
  • Indiana
    • Evansville, Indiana, United States, 47714
      • Novo Nordisk Investigational Site
  • Kansas
    • Newton, Kansas, United States, 67114
      • Novo Nordisk Investigational Site
  • Kentucky
    • Louisville, Kentucky, United States, 40206
      • Novo Nordisk Investigational Site
    • Madisonville, Kentucky, United States, 42431
      • Novo Nordisk Investigational Site
  • Louisiana
    • Marrero, Louisiana, United States, 70072
      • Novo Nordisk Investigational Site
    • Slidell, Louisiana, United States, 70461-4231
      • Novo Nordisk Investigational Site
    • Slidell, Louisiana, United States, 70458
      • Novo Nordisk Investigational Site
  • Maryland
    • Rockville, Maryland, United States, 20852
      • Novo Nordisk Investigational Site
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Novo Nordisk Investigational Site
  • Michigan
    • Buckley, Michigan, United States, 49620
      • Novo Nordisk Investigational Site
  • Mississippi
    • Belzoni, Mississippi, United States, 39038
      • Novo Nordisk Investigational Site
  • Missouri
    • Bridgeton, Missouri, United States, 63044
      • Novo Nordisk Investigational Site
  • Montana
    • Kalispell, Montana, United States, 59901
      • Novo Nordisk Investigational Site
  • Nebraska
    • Elkhorn, Nebraska, United States, 68022
      • Novo Nordisk Investigational Site
  • Nevada
    • Las Vegas, Nevada, United States, 89103
      • Novo Nordisk Investigational Site
  • New Jersey
    • Lawrenceville, New Jersey, United States, 08648
      • Novo Nordisk Investigational Site
  • New York
    • Hopewell Junction, New York, United States, 12553
      • Novo Nordisk Investigational Site
  • North Carolina
    • Statesville, North Carolina, United States, 28625
      • Novo Nordisk Investigational Site
  • Ohio
    • Cincinnati, Ohio, United States, 45255
      • Novo Nordisk Investigational Site
    • Cincinnati, Ohio, United States, 45219
      • Novo Nordisk Investigational Site
    • Cincinnati, Ohio, United States, 45227
      • Novo Nordisk Investigational Site
    • Delaware, Ohio, United States, 43015
      • Novo Nordisk Investigational Site
    • Dublin, Ohio, United States, 43016
      • Novo Nordisk Investigational Site
    • Kettering, Ohio, United States, 45429
      • Novo Nordisk Investigational Site
    • Mason, Ohio, United States, 45040-6815
      • Novo Nordisk Investigational Site
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73112
      • Novo Nordisk Investigational Site
  • Oregon
    • Corvallis, Oregon, United States, 97330-3737
      • Novo Nordisk Investigational Site
  • Pennsylvania
    • Downingtown, Pennsylvania, United States, 19335-2620
      • Novo Nordisk Investigational Site
    • Media, Pennsylvania, United States, 19063
      • Novo Nordisk Investigational Site
    • Smithfield, Pennsylvania, United States, 15478
      • Novo Nordisk Investigational Site
    • Uniontown, Pennsylvania, United States, 15401
      • Novo Nordisk Investigational Site
  • South Carolina
    • Charleston, South Carolina, United States, 29412
      • Novo Nordisk Investigational Site
    • Hodges, South Carolina, United States, 29653
      • Novo Nordisk Investigational Site
    • Indian Land, South Carolina, United States, 29707
      • Novo Nordisk Investigational Site
    • Mount Pleasant, South Carolina, United States, 29464
      • Novo Nordisk Investigational Site
  • Tennessee
    • Bristol, Tennessee, United States, 37620-7352
      • Novo Nordisk Investigational Site
    • Chattanooga, Tennessee, United States, 37404
      • Novo Nordisk Investigational Site
    • Johnson City, Tennessee, United States, 37604
      • Novo Nordisk Investigational Site
    • Kingsport, Tennessee, United States, 37660
      • Novo Nordisk Investigational Site
    • Memphis, Tennessee, United States, 38119-4806
      • Novo Nordisk Investigational Site
    • Nashville, Tennessee, United States, 37203
      • Novo Nordisk Investigational Site
  • Texas
    • Arlington, Texas, United States, 76012-4637
      • Novo Nordisk Investigational Site
    • Austin, Texas, United States, 78705
      • Novo Nordisk Investigational Site
    • Carrollton, Texas, United States, 75010
      • Novo Nordisk Investigational Site
    • Dallas, Texas, United States, 75230
      • Novo Nordisk Investigational Site
    • Dallas, Texas, United States, 75390-9302
      • Novo Nordisk Investigational Site
    • Dallas, Texas, United States, 75251
      • Novo Nordisk Investigational Site
    • Dallas, Texas, United States, 75220
      • Novo Nordisk Investigational Site
    • Houston, Texas, United States, 77008
      • Novo Nordisk Investigational Site
    • Missouri City, Texas, United States, 77459
      • Novo Nordisk Investigational Site
    • New Braunfels, Texas, United States, 78130
      • Novo Nordisk Investigational Site
    • San Antonio, Texas, United States, 78230
      • Novo Nordisk Investigational Site
    • San Antonio, Texas, United States, 78258
      • Novo Nordisk Investigational Site
    • Sugar Land, Texas, United States, 77479
      • Novo Nordisk Investigational Site
    • Waco, Texas, United States, 76710
      • Novo Nordisk Investigational Site
  • Utah
    • Bountiful, Utah, United States, 84010
      • Novo Nordisk Investigational Site
    • Clinton, Utah, United States, 84015
      • Novo Nordisk Investigational Site
    • Riverton, Utah, United States, 84065
      • Novo Nordisk Investigational Site
  • Virginia
    • Richmond, Virginia, United States, 23219
      • Novo Nordisk Investigational Site
    • Virginia Beach, Virginia, United States, 23454
      • Novo Nordisk Investigational Site
    • Winchester, Virginia, United States, 22601
      • Novo Nordisk Investigational Site
  • Washington
    • Renton, Washington, United States, 98057
      • Novo Nordisk Investigational Site
    • Spokane, Washington, United States, 99216-1557
      • 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:

• Male or female, age at least 18 years at the time of signing informed consent.
• Subjects should be on stable diabetes treatment consisting of diet and exercise with or without metformin (at least 1500 mg daily or maximum tolerated dose documented in the patient medical record) for at least 90 days prior to screening
• HbA1c (glycosylated haemoglobin): 53-86 mmol/mol (7.0-10.0%) (both inclusive)
• BMI: 25.0 - 40.0 kg/m^2 (both inclusive)

Exclusion Criteria:

• Simultaneous participation in any other clinical trial of an investigational medicinal product
• Female who is pregnant, breast-feeding or intends to become pregnant or is of child-bearing potential and not using adequate contraceptive methods throughout the trial including the 7 weeks follow-up period (adequate contraceptive measures as required by local regulation or practice). Germany: Only highly effective methods of birth control are accepted (i.e. one that results in less than 1% per year failure rate when used consistently and correctly such as implants, injectables, combined oral contraceptives, some intrauterine device), or sexual abstinence or vasectomised partner. United Kingdom: Adequate contraceptive measures are defined as established use of oral, injected or implanted hormonal methods of contraception, placement of an intrauterine device or intrauterine system, barrier methods of contraception (condom or occlusive cap with spermicidal foam/gel/film/cream/suppository), female sterilisation, male sterilisation (where partner is sole partner of subject), or true abstinence (when in line with preferred and usual lifestyle)
• Treatment with any medication for the indication of diabetes or obesity other than stated in the inclusion criteria in a period of 90 days before screening (an exception is short-term insulin treatment for acute illnesses for a total of below or equal to 14 days)
• Anticipated initiation or change in concomitant medications (for more than 14 consecutive days or on an frequent basis) known to affect weight or glucose metabolism (e.g. orlistat, thyroid hormones, corticosteroids)
• History of pancreatitis (acute or chronic)
• Screening calcitonin above or equal to 50 ng/L
• Family or personal history of Multiple Endocrine Neoplasia Type 2 (MEN2) or Medullary Thyroid Carcinoma (MTC)
• Severe to moderate renal impairment defined as GFR, estimated below 60 ml/min/1.73 m^2 as per CKD-EPI (Chronic Kidney Disease Epidemiology)
• Within the past 180 days before screening any of the following: Myocardial infarction, stroke or hospitalisation for unstable angina and/or transient ischemic attack
• Currently planned coronary, carotid or peripheral artery revascularisation
• Patients presently classified as being in New York Heart Association (NYHA) Class III or IV

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

13

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Semaglutide 0.05 mg/day	Drug: semaglutide; Administered subcutaneously ( s.c., under the skin) once daily. All subjects will follow a 4-week dose-escalation regimen except subjects who received semaglutide flexible dosing.
Active Comparator: Liraglutide 0.3 mg/day	Drug: liraglutide; Administered subcutaneously ( s.c., under the skin) once daily. All subjects will follow a 4-week dose-escalation regimen.
Placebo Comparator: Placebo 50 µL	Drug: placebo; Administered subcutaneously ( s.c., under the skin) once daily.
Experimental: Semaglutide 0.05/0.1 mg/day	Drug: semaglutide; Administered subcutaneously ( s.c., under the skin) once daily. All subjects will follow a 4-week dose-escalation regimen except subjects who received semaglutide flexible dosing.
Active Comparator: Liraglutide 0.3/0.6 mg/day	Drug: liraglutide; Administered subcutaneously ( s.c., under the skin) once daily. All subjects will follow a 4-week dose-escalation regimen.
Placebo Comparator: Placebo 50/100 µL	Drug: placebo; Administered subcutaneously ( s.c., under the skin) once daily.
Experimental: Semaglutide 0.05/0.1/0.2 mg/day	Drug: semaglutide; Administered subcutaneously ( s.c., under the skin) once daily. All subjects will follow a 4-week dose-escalation regimen except subjects who received semaglutide flexible dosing.
Active Comparator: Liraglutide 0.3/0.6/1.2 mg/day	Drug: liraglutide; Administered subcutaneously ( s.c., under the skin) once daily. All subjects will follow a 4-week dose-escalation regimen.
Placebo Comparator: Placebo 50/100/200 µL	Drug: placebo; Administered subcutaneously ( s.c., under the skin) once daily.
Experimental: Semaglutide 0.05/0.1/0.2/0.3 mg/day	Drug: semaglutide; Administered subcutaneously ( s.c., under the skin) once daily. All subjects will follow a 4-week dose-escalation regimen except subjects who received semaglutide flexible dosing.
Active Comparator: Liraglutide 0.3/0.6/1.2/1.8 mg/day	Drug: liraglutide; Administered subcutaneously ( s.c., under the skin) once daily. All subjects will follow a 4-week dose-escalation regimen.
Placebo Comparator: Placebo 50/100/200/300 µL	Drug: placebo; Administered subcutaneously ( s.c., under the skin) once daily.
Experimental: Semaglutide flexible escalation from 0.05 mg/day to 0.3 mg/day	Drug: semaglutide; Administered subcutaneously ( s.c., under the skin) once daily. All subjects will follow a 4-week dose-escalation regimen except subjects who received semaglutide flexible dosing.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in HbA1c (Glycosylated Haemoglobin)	Estimated mean change from baseline in HbA1c at week 26. The data were analysed for the "on-treatment until rescue medication" observation period which includes observations recorded at or after date of first dose of trial product and not after the last dose of trial product plus the 7-day visit window or date of initiation of rescue therapy.	Week 0, week 26

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Fasting Plasma Glucose (FPG)	Estimated mean change from baseline in FPG at week 26. The data were analysed for the "on-treatment until rescue medication" observation period which includes observations recorded at or after date of first dose of trial product and not after the last dose of trial product plus the 7-day visit window or date of initiation of rescue therapy.	Week 0, Week 26
Body Weight Change	The data were analysed for the "on-treatment until rescue medication" observation period which includes observations recorded at or after date of first dose of trial product and not after the last dose of trial product plus the 7-day visit window or date of initiation of rescue therapy.	Week 0, Week 26
Change in Systolic and Diastolic Blood Pressure	The data were analysed for the "on-treatment until rescue medication" observation period which includes observations recorded at or after date of first dose of trial product and not after the last dose of trial product plus the 7-day visit window or date of initiation of rescue therapy.	Week 0, Week 26

Collaborators and Investigators

• Sponsor: Novo Nordisk A/S

Publications and helpful links

General Publications

• Lingvay I, Desouza CV, Lalic KS, Rose L, Hansen T, Zacho J, Pieber TR. A 26-Week Randomized Controlled Trial of Semaglutide Once Daily Versus Liraglutide and Placebo in Patients With Type 2 Diabetes Suboptimally Controlled on Diet and Exercise With or Without Metformin. Diabetes Care. 2018 Sep;41(9):1926-1937. doi: 10.2337/dc17-2381. Epub 2018 Jul 19.

Helpful Links

• Clinical Trials at Novo Nordisk

Study record dates

Study Major Dates

• Study Start (Actual): September 21, 2015
• Primary Completion (Actual): October 13, 2016
• Study Completion (Actual): October 13, 2016

Study Registration Dates

• First Submitted: June 1, 2015
• First Submitted That Met QC Criteria: June 1, 2015
• First Posted (Estimate): June 3, 2015

Study Record Updates

• Last Update Posted (Actual): July 31, 2019
• Last Update Submitted That Met QC Criteria: July 30, 2019
• Last Verified: July 1, 2019

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; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Incretins; Liraglutide
• Other Study ID Numbers: NN9535-4191; 2014-003196-39 (EudraCT Number); U1111-1159-4923 (Other Identifier: WHO)