Research Study Comparing a New Medicine "Fast-acting Insulin Aspart" to Another Already Available Medicine "NovoRapid"/"NovoLog" in People With Type 2 Diabetes (onset 9)

Efficacy and Safety of Fast-acting Insulin Aspart Compared to NovoRapid® Both in Combination With Insulin Degludec With or Without Metformin in Adults With Type 2 Diabetes (Onset® 9)

The study compares 2 medicines for type 2 diabetes: fast-acting insulin aspart (a new medicine) and NovoRapid®/NovoLog® (a medicine doctors can already prescribe). Fast-acting insulin aspart will be tested to see how well it works and if it is safe. Participants will get either fast-acting insulin aspart or NovoRapid®/ NovoLog® - which treatment you get is decided by chance. Both medicines will be taken together with insulin degludec. Participants will need to take 1 injection 4 times every day (all insulins will be provided in pens). The study will last for about 8 months (34 weeks).

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus, Type 2; Diabetes
• Intervention / Treatment: Drug: Faster-acting insulin aspart; Drug: Insulin degludec; Drug: Metformin; Drug: Insulin aspart

• Study Type: Interventional
• Enrollment (Actual): 1264
• Phase: Phase 3

Contacts and Locations

Study Locations

• Argentina
  • Caba, Argentina, C1060ABA
    • Novo Nordisk Investigational Site
  • Caba, Argentina, C1440AAD
    • Novo Nordisk Investigational Site
  • Cordoba, Argentina, 5000
    • Novo Nordisk Investigational Site
  • Córdoba, Argentina, 5008
    • Novo Nordisk Investigational Site
• Bulgaria
  • Kozloduy, Bulgaria, 3320
    • Novo Nordisk Investigational Site
  • Razgrad, Bulgaria, 7200
    • Novo Nordisk Investigational Site
  • Sofia, Bulgaria, 1233
    • Novo Nordisk Investigational Site
  • Sofia, Bulgaria, 1618
    • Novo Nordisk Investigational Site
• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 2E1
      • Novo Nordisk Investigational Site
  • British Columbia
    • Victoria, British Columbia, Canada, V8V 4A1
      • Novo Nordisk Investigational Site
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3H 2Y9
      • Novo Nordisk Investigational Site
  • Ontario
    • Barrie, Ontario, Canada, L4N 7L3
      • Novo Nordisk Investigational Site
    • Concord, Ontario, Canada, L4K 4M2
      • Novo Nordisk Investigational Site
    • Etobicoke, Ontario, Canada, M9R 4E1
      • Novo Nordisk Investigational Site
    • Hamilton, Ontario, Canada, L8M 1K7
      • Novo Nordisk Investigational Site
    • Newmarket, Ontario, Canada, L3Y 5G8
      • Novo Nordisk Investigational Site
    • Thunder Bay, Ontario, Canada, P7A 4V7
      • Novo Nordisk Investigational Site
    • Toronto, Ontario, Canada, M4G 3E8
      • Novo Nordisk Investigational Site
  • Quebec
    • Montreal, Quebec, Canada, H4T 1Z9
      • Novo Nordisk Investigational Site
• Croatia
  • Karlovac, Croatia, 47000
    • Novo Nordisk Investigational Site
  • Osijek, Croatia, 31 000
    • Novo Nordisk Investigational Site
  • Varazdin, Croatia, 42 000
    • Novo Nordisk Investigational Site
  • Zagreb, Croatia, 10 000
    • Novo Nordisk Investigational Site
• Czechia
  • Hradec Kralove, Czechia, 500 05
    • Novo Nordisk Investigational Site
  • Plzen, Czechia, 30100
    • Novo Nordisk Investigational Site
  • Plzen, Czechia, 32600
    • Novo Nordisk Investigational Site
  • Trutnov, Czechia, 541 01
    • Novo Nordisk Investigational Site
• Germany
  • Dresden, Germany, 01219
    • Novo Nordisk Investigational Site
  • Essen, Germany, 45136
    • Novo Nordisk Investigational Site
  • Falkensee, Germany, 14612
    • Novo Nordisk Investigational Site
  • Lingen, Germany, 49808
    • Novo Nordisk Investigational Site
  • Münster, Germany, 48145
    • Novo Nordisk Investigational Site
  • Saint Ingbert-Oberwürzbach, Germany, 66386
    • Novo Nordisk Investigational Site
  • Schweinfurt, Germany, 97421
    • Novo Nordisk Investigational Site
• Greece
  • Athens, Greece, GR-11527
    • Novo Nordisk Investigational Site
  • Athens, Greece, 115 25
    • Novo Nordisk Investigational Site
  • Ioannina, Greece, 45500
    • Novo Nordisk Investigational Site
  • Larissa, Greece, GR-41110
    • Novo Nordisk Investigational Site
  • Thessaloniki, Greece, GR-54636
    • Novo Nordisk Investigational Site
  • Thessaloniki, Greece, GR-57001
    • Novo Nordisk Investigational Site
  • Thessaloniki, Greece, GR-54642
    • Novo Nordisk Investigational Site
  • Thessaloniki, Greece, GR-54643
    • Novo Nordisk Investigational Site
• Italy
  • Catanzaro, Italy, 88100
    • Novo Nordisk Investigational Site
  • Chieti, Italy, 66100
    • Novo Nordisk Investigational Site
  • Cittadella (PD), Italy, 35013
    • Novo Nordisk Investigational Site
  • Milano (MI), Italy, 20132
    • Novo Nordisk Investigational Site
  • Olbia, Italy, 07026
    • Novo Nordisk Investigational Site
  • Palermo, Italy, 90129
    • Novo Nordisk Investigational Site
• Korea, Republic of
  • Bucheon, Korea, Republic of, 14647
    • Novo Nordisk Investigational Site
  • Daegu, Korea, Republic of, 42472
    • Novo Nordisk Investigational Site
  • Seongnam-si, Korea, Republic of, 463-707
    • Novo Nordisk Investigational Site
  • Seoul, Korea, Republic of, 02447
    • Novo Nordisk Investigational Site
  • Seoul, Korea, Republic of, 03080
    • Novo Nordisk Investigational Site
  • Seoul, Korea, Republic of, 04516
    • Novo Nordisk Investigational Site
  • Seoul, Korea, Republic of, 06351
    • Novo Nordisk Investigational Site
  • Seoul, Korea, Republic of, 08308
    • Novo Nordisk Investigational Site
  • Seoul, Korea, Republic of, 137-701
    • Novo Nordisk Investigational Site
  • Wonju, Korea, Republic of, 26426
    • Novo Nordisk Investigational Site
• Poland
  • Bialystok, Poland, 15-435
    • Novo Nordisk Investigational Site
  • Skorzewo, Poland, 60-185
    • Novo Nordisk Investigational Site
  • Warsaw, Poland, 00-465
    • Novo Nordisk Investigational Site
  • Warsaw, Poland, 02-793
    • Novo Nordisk Investigational Site
  • Warszawa, Poland, 02-507
    • Novo Nordisk Investigational Site
  • Wroclaw, Poland, 50-381
    • Novo Nordisk Investigational Site
• Puerto Rico
  • Ponce, Puerto Rico, 00716
    • Novo Nordisk Investigational Site
• Romania
  • Brasov, Romania, 500101
    • Novo Nordisk Investigational Site
  • Brasov, Romania, 500283
    • Novo Nordisk Investigational Site
  • Bucharest, Romania, 13682
    • Novo Nordisk Investigational Site
  • Maramures
    • Baia Mare, Maramures, Romania, 430222
      • Novo Nordisk Investigational Site
  • Mures
    • Tirgu Mures, Mures, Romania, 540142
      • Novo Nordisk Investigational Site
  • Timis
    • Timisoara, Timis, Romania, 300125
      • Novo Nordisk Investigational Site
• Russian Federation
  • Arkhangelsk, Russian Federation, 163045
    • Novo Nordisk Investigational Site
  • Kazan, Russian Federation, 420073
    • Novo Nordisk Investigational Site
  • Moscow, Russian Federation, 123448
    • Novo Nordisk Investigational Site
  • Penza, Russian Federation, 440026
    • Novo Nordisk Investigational Site
  • Saint Petersburg, Russian Federation, 194291
    • Novo Nordisk Investigational Site
  • Saint-Petersburg, Russian Federation, 194356
    • Novo Nordisk Investigational Site
  • Tumen, Russian Federation, 625023
    • 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
• Slovakia
  • Kosice, Slovakia, 040 01
    • Novo Nordisk Investigational Site
  • Kysucke Nove Mesto, Slovakia, 024 01
    • Novo Nordisk Investigational Site
  • Lubochna, Slovakia, 03491
    • Novo Nordisk Investigational Site
  • Lucenec, Slovakia, 984 01
    • Novo Nordisk Investigational Site
  • Zilina, Slovakia, 01001
    • Novo Nordisk Investigational Site
• Spain
  • Alcobendas, Spain, 28100
    • Novo Nordisk Investigational Site
  • Almería, Spain, 04001
    • Novo Nordisk Investigational Site
  • Girona, Spain, 17007
    • Novo Nordisk Investigational Site
  • La Coruña, Spain, 15006
    • Novo Nordisk Investigational Site
  • Pozuelo de Alarcon, Spain, 28223
    • Novo Nordisk Investigational Site
  • Sabadell, Spain, 08208
    • Novo Nordisk Investigational Site
  • Sevilla, Spain, 41010
    • Novo Nordisk Investigational Site
  • Sevilla, Spain, 41003
    • Novo Nordisk Investigational Site
• Ukraine
  • Dnipro, Ukraine, 49038
    • Novo Nordisk Investigational Site
  • Kharkiv, Ukraine, 61000
    • Novo Nordisk Investigational Site
  • Kyiv, Ukraine, 03049
    • Novo Nordisk Investigational Site
  • Lviv, Ukraine, 79010
    • Novo Nordisk Investigational Site
  • Ternopil, Ukraine, 46002
    • Novo Nordisk Investigational Site
  • Vinnytsia, Ukraine, 21010
    • Novo Nordisk Investigational Site
• United States
  • California
    • Concord, California, United States, 94520
      • Novo Nordisk Investigational Site
    • Fresno, California, United States, 93720
      • Novo Nordisk Investigational Site
    • Fullerton, California, United States, 92835
      • Novo Nordisk Investigational Site
    • Lancaster, California, United States, 93534
      • Novo Nordisk Investigational Site
    • Norco, California, United States, 92860
      • Novo Nordisk Investigational Site
    • Sacramento, California, United States, 95821
      • Novo Nordisk Investigational Site
    • Ventura, California, United States, 93003
      • Novo Nordisk Investigational Site
    • Walnut Creek, California, United States, 94598
      • Novo Nordisk Investigational Site
  • Colorado
    • Denver, Colorado, United States, 80246
      • Novo Nordisk Investigational Site
    • Golden, Colorado, United States, 80401
      • Novo Nordisk Investigational Site
  • Connecticut
    • Waterbury, Connecticut, United States, 06708
      • Novo Nordisk Investigational Site
  • Florida
    • Boynton Beach, Florida, United States, 33472
      • Novo Nordisk Investigational Site
    • Bradenton, Florida, United States, 34201
      • Novo Nordisk Investigational Site
    • Fort Lauderdale, Florida, United States, 33312
      • Novo Nordisk Investigational Site
    • Miami, Florida, United States, 33174
      • Novo Nordisk Investigational Site
    • Tampa, Florida, United States, 33634
      • Novo Nordisk Investigational Site
  • Georgia
    • Alpharetta, Georgia, United States, 30022
      • Novo Nordisk Investigational Site
    • Lawrenceville, Georgia, United States, 30046
      • Novo Nordisk Investigational Site
    • Roswell, Georgia, United States, 30076
      • Novo Nordisk Investigational Site
  • Hawaii
    • Honolulu, Hawaii, United States, 96814
      • Novo Nordisk Investigational Site
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Novo Nordisk Investigational Site
    • Peoria, Illinois, United States, 61603
      • Novo Nordisk Investigational Site
    • Springfield, Illinois, United States, 62711
      • Novo Nordisk Investigational Site
  • Indiana
    • Valparaiso, Indiana, United States, 46383
      • Novo Nordisk Investigational Site
  • Iowa
    • West Des Moines, Iowa, United States, 50266
      • Novo Nordisk Investigational Site
  • Kansas
    • Topeka, Kansas, United States, 66606
      • Novo Nordisk Investigational Site
  • Kentucky
    • Lexington, Kentucky, United States, 40503
      • Novo Nordisk Investigational Site
    • Lexington, Kentucky, United States, 40502
      • Novo Nordisk Investigational Site
  • Maryland
    • Rockville, Maryland, United States, 20852
      • Novo Nordisk Investigational Site
  • Massachusetts
    • Waltham, Massachusetts, United States, 02453
      • Novo Nordisk Investigational Site
    • Worcester, Massachusetts, United States, 01655
      • Novo Nordisk Investigational Site
  • Nevada
    • Henderson, Nevada, United States, 89052-2649
      • Novo Nordisk Investigational Site
    • Las Vegas, Nevada, United States, 89148
      • Novo Nordisk Investigational Site
  • New Hampshire
    • Nashua, New Hampshire, United States, 03063
      • Novo Nordisk Investigational Site
  • New York
    • Northport, New York, United States, 11768
      • Novo Nordisk Investigational Site
    • West Seneca, New York, United States, 14224
      • Novo Nordisk Investigational Site
  • North Carolina
    • Asheville, North Carolina, United States, 28803
      • Novo Nordisk Investigational Site
    • Chapel Hill, North Carolina, United States, 27514
      • Novo Nordisk Investigational Site
  • Ohio
    • Mentor, Ohio, United States, 44060
      • Novo Nordisk Investigational Site
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104-5020
      • Novo Nordisk Investigational Site
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19140
      • Novo Nordisk Investigational Site
  • South Carolina
    • Greenville, South Carolina, United States, 29605-4254
      • Novo Nordisk Investigational Site
  • Tennessee
    • Chattanooga, Tennessee, United States, 37404
      • Novo Nordisk Investigational Site
    • Chattanooga, Tennessee, United States, 37411
      • Novo Nordisk Investigational Site
    • Nashville, Tennessee, United States, 37212
      • Novo Nordisk Investigational Site
  • Texas
    • Amarillo, Texas, United States, 79106
      • Novo Nordisk Investigational Site
    • Austin, Texas, United States, 78731
      • Novo Nordisk Investigational Site
    • Austin, Texas, United States, 78749
      • Novo Nordisk Investigational Site
    • Beaumont, Texas, United States, 77701
      • Novo Nordisk Investigational Site
    • Dallas, Texas, United States, 75230
      • Novo Nordisk Investigational Site
    • Dallas, Texas, United States, 75226
      • Novo Nordisk Investigational Site
    • Dallas, Texas, United States, 75231
      • Novo Nordisk Investigational Site
    • Longview, Texas, United States, 75605
      • Novo Nordisk Investigational Site
    • Pearland, Texas, United States, 77584
      • Novo Nordisk Investigational Site
    • Round Rock, Texas, United States, 78681
      • Novo Nordisk Investigational Site
  • Utah
    • Ogden, Utah, United States, 84405
      • Novo Nordisk Investigational Site
  • Vermont
    • Bennington, Vermont, United States, 05201
      • Novo Nordisk Investigational Site
    • South Burlington, Vermont, United States, 05403
      • Novo Nordisk Investigational Site
  • Virginia
    • Chesapeake, Virginia, United States, 23321
      • Novo Nordisk Investigational Site
    • Winchester, Virginia, United States, 22601-3834
      • Novo Nordisk Investigational Site
  • Washington
    • Olympia, Washington, United States, 98502
      • Novo Nordisk Investigational Site
    • Seattle, Washington, United States, 98105
      • Novo Nordisk Investigational Site
    • Spokane, Washington, United States, 99201
      • Novo Nordisk Investigational Site
  • Wisconsin
    • Green Bay, Wisconsin, United States, 54303
      • 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 equal to or above 18 years at the time of signing informed consent. - Diagnosed with type 2 diabetes mellitus for 10 years or longer prior to screening (Visit 1). - Treated with a basal-bolus insulin regimen for 1 year or longer prior to the day of screening (Visit 1). A basal-bolus insulin regimen is defined as basal insulin once or twice daily and bolus insulin analogue taken with meals at least 3 times daily. Treatment with premixed insulin or soluble insulin combination is not considered a basal-bolus regimen. - Treated with or without oral antidiabetic drugs including extended release formulations. - HbA1c 7.0-10.0% (both inclusive) as assessed by central laboratory at screening (Visit 1). Exclusion Criteria: - Any of the following: myocardial infarction, stroke, hospitalization for unstable angina or transient ischaemic attack within the past 180 days prior to the day of screening (Visit 1). - Subjects presently classified as being in New York Heart Association (NYHA) Class IV. - Planned coronary, carotid or peripheral artery revascularisation known on the day of screening (Visit 1). - Treatment with injectable GLP-1 receptor agonists in a period of 90 days prior to screening (Visit 1). - Anticipated initiation or change in concomitant medications (for more than 14 consecutive days) known to affect weight or glucose metabolism (e.g. treatment with orlistat, thyroid hormones, or corticosteroids).

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Faster aspart + insulin degludec with or without metformin	Drug: Faster-acting insulin aspart; Faster aspart given subcutaneously (s.c., under the skin) once a day for 16 weeks. Dose individually adjusted.; Drug: Insulin degludec; Insulin degludec given subcutaneously (s.c., under the skin) once a day for 16 weeks. Dose individually adjusted.; Drug: Metformin; Only participants who took metformin before the study should take metformin tablets, same dose as before the study
Active Comparator: NovoRapid/NovoLog + insulin degludec with or without metformin	Drug: Insulin degludec; Insulin degludec given subcutaneously (s.c., under the skin) once a day for 16 weeks. Dose individually adjusted.; Drug: Metformin; Only participants who took metformin before the study should take metformin tablets, same dose as before the study; Drug: Insulin aspart; Insulin aspart given subcutaneously (s.c., under the skin) once a day for 16 weeks. Dose individually adjusted.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Glycosylated Haemoglobin (HbA1c)	Change from baseline (week 0) in glycosylated haemoglobin (HbA1c) was evaluated at week 16. The endpoint was evaluated based on data from the in-trial observation period. In-trial observation period was from date of randomisation and until last trial-related participant-site contact.	Week 0, week 16

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in 1-hour PPG Increment	Change from baseline (week 0) in 1-hour postprandial glucose (PPG) increment was evaluated after 16 weeks of randomisation. The results are based on the last in-trial value, which included the last available measurement in the in-trial period. In trial observation period was from date of randomisation and until last trial-related participant-site contact.	Week 0, week 16
Change From Baseline in 1,5-anhydroglucitol	Change from baseline (week 0) in 1,5-anhydroglucitol was evaluated after 16 weeks of randomisation. The results are based on the last in-trial value, which included the last available measurement in the in-trial period. In trial observation period was from date of randomisation and until last trial-related participant-site contact.	Week 0, week 16
Change From Baseline in Fasting Plasma Glucose (FPG)	Change from baseline (week 0) in fasting plasma glucose was evaluated after 16 weeks of randomisation. The results are based on the last in-trial value, which included the last available measurement in the in-trial period. In trial observation period was from date of randomisation and until last trial-related participant-site contact.	Week 0, week 16
Participants Who Achieved HbA1c <7.0% (53 mmol/L) (Yes/No)	Number of participants reaching HbA1c <7.0% (53 mmol/L) was evaluated after 16 weeks of randomisation. The results are based on the last in-trial value, which included the last available measurement in the in-trial period. In trial observation period was from date of randomisation and until last trial-related participant-site contact.	16 weeks after randomisation
Participants Who Achieved HbA1c <7.0% (53 mmol/L) Without Severe Hypoglycaemia Episodes (Yes/No)	Number of participants reaching HbA1c <7.0% (53 mmol/L) without severe hypoglycaemia episodes was evaluated after 16 weeks of randomisation. The results are based on the last in-trial value, which included the last available measurement in the in-trial period. In trial observation period was from date of randomisation and until last trial-related participant-site contact.	16 weeks after randomisation
Change From Baseline (Week 0) in 30-minute, 1-hour, 2-hour, 3-hour and 4-hour Postprandial Glucose (PPG [Meal Test])	Change from baseline (week 0) in 30-minute, 1-hour, 2-hour, 3-hour and 4-hour postprandial glucose (PPG [meal test]) was evaluated after 16 weeks of randomisation. The results are based on the last in-trial value, which included the last available measurement in the in-trial period. In trial observation period was from date of randomisation and until last trial-related participant-site contact. Meal test: The subjects were given a carbohydrate-rich standardised liquid meal immediately after bolus (faster aspart or NovoRapid) infusion in the morning of the meal test. The subjects were to consume the meal as quickly as possible (within 12 minutes) and blood samples were drawn after 30 minutes, 1, 2, 3 and 4 hours from the start of the meal.	Week 0, week 16
Change From Baseline (Week 0) in 30-minute, 1-hour, 2-hour, 3-hour and 4-hour PPG Increment (Meal Test)	Change from baseline (week 0) in 30-minute, 1-hour, 2-hour, 3-hour and 4-hour PPG increment (meal test) was evaluated after 16 weeks of randomisation. The results are based on the last in-trial value, which included the last available measurement in the in-trial period. In trial observation period was from date of randomisation and until last trial-related participant-site contact. Meal test: The subjects were given a carbohydrate-rich standardised liquid meal immediately after bolus (faster aspart or NovoRapid) infusion in the morning of the meal test. The subjects were to consume the meal as quickly as possible (within 12 minutes) and blood samples were drawn after 30 minutes, 1, 2, 3 and 4 hours from the start of the meal. PPG incremental value for each time point was derived as PPG value at that time point minus the preprandial glucose value.	Week 0, week 16
Change From Baseline in Mean of the 7-9-7 Point Self-measured Plasma Glucose (SMPG) Profile	Change from baseline (week 0) in mean of the 7-9-7 point SMPG profile was evaluated after 16 weeks of randomisation. The results are based on the last in-trial value, which included the last available measurement in the in-trial period. 7-9-7 point SMPG was measured at the following mentioned time points: 1) Before breakfast, 2) 60 mins after the start of Breakfast, 3) Before lunch, 4) 60 mins after the start of lunch, 5) Before main evening meal, 6) 60 mins after the start of main evening meal, 7) At bedtime, 8) At 4 AM, 9) Before breakfast.	Week 0, week 16
Change From Baseline of the 7-9-7 Point SMPG Profile: PPG (Mean, Breakfast, Lunch and Main Evening Meal)	Change from baseline (week 0) in PPG (breakfast, lunch, main evening meal and mean over all meals) of the 7-9-7 point SMPG profile was evaluated after 16 weeks of randomisation. The results are based on the last in-trial value, which included the last available measurement in the in-trial period. In trial observation period was from date of randomisation and until last trial-related participant-site contact.	Week 0, week 16
Change From Baseline of the 7-9-7 Point SMPG Profile: PPG Increment (Mean, Breakfast, Lunch and Main Evening Meal)	Change from baseline (week 0) in PPG increment (breakfast, lunch, main evening meal and mean over all meals) of the 7-9-7 point SMPG profile was evaluated after 16 weeks of randomisation. The results are based on the last in-trial value, which included the last available measurement in the in-trial period. PPG increment based on the 7-9-7-point profiles were derived separately for PG measurements made at 1 hour after main meals (breakfast, lunch and main evening meal). PPG incremental value for each time point was derived as PPG value at that time point minus the preprandial glucose value. In trial observation period was from date of randomisation and until last trial-related participant-site contact.	Week 0, week 16
Change From Baseline of the 7-9-7 Point SMPG Profile: Fluctuation in 7-9-7 Point Profile	Fluctuation in 7-point SMPG profile was the average absolute difference from the mean of the SMPG profile. Reported results are fluctuation in the 7-9-7 point SMPG profile from baseline (week 0) after 16 weeks of randomisation (i.e., week 16). The results are presented as ratio to baseline. The results are based on the last in-trial value, which included the last available measurement in the in-trial period. In trial observation period was from date of randomisation and until last trial-related participant-site contact.	Week 0, week 16
Change From Baseline of the 7-9-7 Point SMPG Profile: Nocturnal SMPG Measurements	Change from baseline (week 0) in nocturnal SMPG measurements was assessed by considering the differences between PG values available at bedtime, at 4 AM and the before breakfast value the following day: (4 AM PG value minus at bedtime PG value), (before breakfast PG value minus at bedtime PG value) and (before breakfast PG value minus 4 AM PG value). Change from baseline in nocturnal increments in SMPG measurements of the 7-9-7 point SMPG profile was evaluated after 16 weeks of randomisation and presented during three different time intervals as follows: 1) 04:00 to breakfast, 2) bedtime to 04:00, and 3) bedtime to breakfast. The results are based on the last in-trial value, which included the last available measurement in the in-trial period. In trial observation period was from date of randomisation and until last trial-related participant-site contact.	Week 0, week 16
Participants Who Achieved Overall PPG (1 Hour) <7.8 mmol/L (140 mg/dL) (Yes/No)	Participants reaching overall PPG (1 hour) ≤7.8 mmol/L [140 mg/dL] was evaluated after 16 weeks of randomisation. Participants without a postprandial glucose measurement at week 16 were considered not to have achieved HbA1c target at week 16. The results are based on the last in-trial value, which included the last available measurement in the in-trial period. In trial observation period was from date of randomisation and until last trial-related participant-site contact.	16 weeks after randomisation
Participants Who Achieved Overall PPG <7.8 mmol/L (140 mg/dL) Without Severe Hypoglycaemia Episodes (Yes/No)	Participants reaching overall PPG (1 hour) ≤7.8 mmol/L [140 mg/dL] without severe hypoglycaemia episodes was evaluated after 16 weeks of randomisation. Participants without a postprandial glucose measurement at week 16 were considered not to have achieved HbA1c target at week 16. The results are based on the last in-trial value, which included the last available measurement in the in-trial period. In trial observation period was from date of randomisation and until last trial-related participant-site contact.	16 weeks after randomisation
Total Bolus Insulin Dose: in Units/Day	Total bolus insulin dose (Units/day) was evaluated after 16 weeks of randomisation. The results are based on the last on-treatment value, which included the last available measurement in the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.	16 weeks from randomisation
Total Bolus Insulin Dose: in Units/kg/Day	Total bolus insulin dose (Units/kg/day) was evaluated after 16 weeks of randomisation. The results are based on the last on-treatment value, which included the last available measurement in the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.	16 weeks from randomisation
Total Basal Insulin Dose: in Units/Day	Total basal insulin dose (Units/day) was evaluated after 16 weeks of randomisation. The results are based on the last on-treatment value, which included the last available measurement in the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.	16 weeks from randomisation
Total Basal Insulin Dose: in Units/kg/Day	Total basal insulin dose (Units/kg/day) was evaluated after 16 weeks of randomisation. The results are based on the last on-treatment value, which included the last available measurement in the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.	16 weeks from randomisation
Individual Meal Insulin Dose: in Units	Individual meal time bolus insulin dose (Units) for breakast, lunch and main evening meal was evaluated after 16 weeks of randomisation. The results are based on the last on-treatment value, which included the last available measurement in the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.	16 weeks from randomisation
Individual Meal Insulin Dose: in Units/kg	Individual meal time bolus insulin dose (Units/kg) for breakast, lunch and main evening meal was evaluated after 16 weeks of randomisation. The results are based on the last on-treatment value, which included the last available measurement in the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.	16 weeks from randomisation
Change From Baseline in Lipids-lipoproteins Profile (Total Cholesterol, High Density Lipoproteins, Low Density Lipoproteins) - Ratio to Baseline	Reported results are lipids-lipoproteins (total cholesterol, high density lipoproteins, low density lipoproteins) values are given as ratio to baseline (week 0) after 16 weeks. The results are based on the last in-trial value, which included the last available measurement in the in-trial period. In trial observation period was from date of randomisation and until last trial-related participant-site contact.	Week 0, week 16
Number of Treatment Emergent Adverse Events	Number of treatment emergent adverse events were recorded from week 0 to week 16. The results are based on the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.	Weeks 0-16
Number of Treatment Emergent Injection Site Reactions	Number of treatment emergent injection site reactions were recorded from week 0 to week 16. The results are based on the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.	Weeks 0-16
Number of Treatment Emergent Hypoglycaemic Episodes (Hypos) According to the American Diabetes Association (ADA) and Novo Nordisk (NN) Definition: Overall	ADA classification of hypos: Severe: Requiring assistance of another person to actively administer carbohydrate/glucagon/take other corrective actions. PG levels may not be available during an event, but neurological recovery following return of PG to normal is considered sufficient evidence that event was induced by a low PG level.; Documented symptomatic: PG ≤3.9 mmol/L with symptoms.; Asymptomatic: PG ≤3.9 mmol/L without symptoms.; Probable symptomatic: No measurement with symptoms.; Pseudo: PG >3.9 mmol/L with symptoms.; Unclassifiable. NN classification of hypos: BG confirmed: PG <3.1 mmol/L with/without symptoms.; Severe or BG confirmed symptomatic: Severe as per ADA and BG confirmed by PG <3.1 mmol/L with symptoms.; Severe or BG confirmed: Severe as per ADA and BG confirmed by PG <3.1 mmol/L with/without symptoms.; Unclassifiable. Not able to self treat-unclassifiable: Not able to self treat but not classifiable as severe hypoglycaemia.	Weeks 0-16
Number of Treatment Emergent Hypoglycaemic Episodes According to the American Diabetes Association and Novo Nordisk Definition: Daytime Hypoglycaemic Episodes (06:00-00:00 - Inclusive)	Number of treatment emergent day time hypoglycaemic episodes according to the ADA and NN definitions were evaluated between 06:00 and 00:00 (both included). The results are based on the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.	Weeks 0-16
Number of Treatment Emergent Hypoglycaemic Episodes According to the American Diabetes Association and Novo Nordisk Definition: Nocturnal Hypoglycaemic Episodes (00:01-05:59 - Inclusive)	Number of treatment emergent nocturnal hypoglycaemic episodes according to the ADA and NN definitions were evaluated between 00:01 and 05:59 (both included). The results are based on the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.	Weeks 0-16
Number of Treatment Emergent Hypoglycaemic Episodes According to the American Diabetes Association and Novo Nordisk Definition: Hypoglycaemic Episodes During First 1 Hour After Start of the Meal	Number of treatment emergent hypoglycaemic episodes according to the ADA and NN definitions were evaluated during the first 1 hour after start of the meal. The results are based on the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.	Weeks 0-16
Number of Treatment Emergent Hypoglycaemic Episodes According to the American Diabetes Association and Novo Nordisk Definition: Hypoglycaemic Episodes During First 2 Hours After Start of the Meal	Number of treatment emergent hypoglycaemic episodes according to the ADA and NN definitions were evaluated during the first 2 hours after start of the meal. The results are based on the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.	Weeks 0-16
Number of Treatment Emergent Hypoglycaemic Episodes According to the American Diabetes Association and Novo Nordisk Definition: Hypoglycaemic Episodes During First 4 Hours After Start of the Meal	Number of treatment emergent hypoglycaemic episodes according to the ADA and NN definitions were evaluated during the first 4 hours after start of the meal. The results are based on the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.	Weeks 0-16
Number of Treatment Emergent Hypoglycaemic Episodes According to the American Diabetes Association and NN Definition: Hypoglycaemic Episodes Occurring Between 2 to 4 Hours After Start of the Meal	Number of treatment emergent hypoglycaemic episodes according to the ADA and NN definitions were evaluated between 2 to 4 hours after start of the meal. The results are based on the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.	Weeks 0-16
Change From Baseline in Physical Examination	Participants with physical examination findings, normal, abnormal NCS (non- clinically significant) and abnormal CS (clinically significant) at baseline (week 0) and week 16 presented. Results are based on the data from the on-treatment observation period, which was the time period from when a participant was randomised until the final scheduled visit, including any period after initiation of rescue medication and/or premature discontinuation of trial product. Results are presented for the following examinations: 1) Cardiovascular system 2) Central & Peripheral nervous system 3) Gastrointestinal system incl. mouth 4) Head, ears, eyes, nose, throat and neck 5) Musculoskeletal system 6) Respiratory system 7) Skin	Week 0, week 16
Change From Baseline in Vital Signs: Systolic and Diastolic Blood Presure	Change in vital signs - systolic and diastolic blood pressure from baseline (week 0) was evaluated after 16 weeks of randomisation. The results are based on the last on-treatment value, which included the last available measurement in the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.	Week 0, week 16
Change From Baseline in Vital Signs: Pulse	Change in vital signs - pulse from baseline (week 0) was evaluated after 16 weeks of randomisation. The results are based on the last on-treatment value, which included the last available measurement in the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.	Week 0, week 16
Change From Baseline in Electrocardiogram (ECG)	Changes in electrocardiogram (ECG) from baseline (week 0) were evaluated after 16 weeks of randomisation. The results are based on the last on-treatment value, which included the last available measurement in the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.	Week 0, week 16
Change From Baseline in Fundoscopy/Fundus Photography	Changes in fundoscopy/fundus photography from baseline (week 0) were evaluated after 16 weeks of randomisation. The results are based on the last on-treatment value, which included the last available measurement in the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.	Week 0, week 16
Change From Baseline in Haematology - Haematocrit	Changes in haematology - haematocrit from baseline (week 0) were evaluated after 16 weeks of randomisation. The results are based on the last on-treatment value, which included the last available measurement in the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.	Week 0, week 16
Change From Baseline in Haematology - Haemoglobin	Changes in haematology - haemoglobin from baseline (week 0) were evaluated after 16 weeks of randomisation. The results are based on the last on-treatment value, which included the last available measurement in the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.	Week 0, week 16
Change From Baseline in Haematology - Leukocytes	Changes in haematology - leukocytes from baseline (week 0) were evaluated after 16 weeks of randomisation. The results are based on the last on-treatment value, which included the last available measurement in the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.	Week 0, week 16
Change From Baseline in Haematology - Thrombocytes	Changes in haematology - thrombocytes from baseline (week 0) were evaluated after 16 weeks of randomisation. The results are based on the last on-treatment value, which included the last available measurement in the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.	Week 0, week 16
Change From Baseline in Haematology - Erythrocytes	Changes in haematology - erythrocytes from baseline (week 0) were evaluated after 16 weeks of randomisation. The results are based on the last on-treatment value, which included the last available measurement in the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.	Week 0, week 16
Change From Baseline in Biochemistry - Alanine Aminotransferase (ALT)	Changes in biochemistry - alanine aminotransferase from baseline (week 0) were evaluated after 16 weeks of randomisation. The results are based on the last on-treatment value, which included the last available measurement in the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.	Week 0, week 16
Change From Baseline in Biochemistry - Alkaline Phosphatase	Changes in biochemistry - alkaline phosphatase from baseline (week 0) were evaluated after 16 weeks of randomisation. The results are based on the last on-treatment value, which included the last available measurement in the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.	Week 0, week 16
Change From Baseline in Biochemistry - Aspartate Aminotransferase (AST)	Changes in biochemistry - aspratate aminotransferase from baseline (week 0) were evaluated after 16 weeks of randomisation. The results are based on the last on-treatment value, which included the last available measurement in the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.	Week 0, week 16
Change From Baseline in Biochemistry - Albumin	Changes in biochemistry - albumin from baseline (week 0) were evaluated after 16 weeks of randomisation. The results are based on the last on-treatment value, which included the last available measurement in the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.	Week 0, week 16
Change From Baseline in Biochemistry - Creatinine	Changes in biochemistry - creatinine from baseline (week 0) were evaluated after 16 weeks of randomisation. The results are based on the last on-treatment value, which included the last available measurement in the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.	Week 0, week 16
Change From Baseline in Biochemistry - Potassium	Changes in biochemistry - potassium from baseline (week 0) were evaluated after 16 weeks of randomisation. The results are based on the last on-treatment value, which included the last available measurement in the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.	Week 0, week 16
Change From Baseline in Biochemistry - Sodium	Changes in biochemistry - sodium from baseline (week 0) were evaluated after 16 weeks of randomisation. The results are based on the last on-treatment value, which included the last available measurement in the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.	Week 0, week 16
Change From Baseline in Biochemistry - Total Bilirubin	Changes in biochemistry - total bilirubin from baseline (week 0) were evaluated after 16 weeks of randomisation. The results are based on the last on-treatment value, which included the last available measurement in the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.	Week 0, week 16
Change From Baseline in Biochemistry - Total Protein	Changes in biochemistry - total protein from baseline (week 0) were evaluated after 16 weeks of randomisation. The results are based on the last on-treatment value, which included the last available measurement in the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.	Week 0, week 16
Change From Baseline in Body Weight	Changes in body weight from baseline (week 0) were evaluated after 16 weeks of randomisation. The results are based on the last on-treatment value, which included the last available measurement in the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.	Week 0, week 16
Change From Baseline in Body Mass Index (BMI)	Change in the body mass index (BMI) from baseline (week 0) were evaluated after 16 weeks of randomisation. The results are based on the last on-treatment value, which included the last available measurement in the on-treatment period. On-treatment period started from date of first dose of randomised NovoRapid/faster aspart and to 7 days after day of last dose or day before initiation of ancillary treatment.	Week 0, week 16

Collaborators and Investigators

• Sponsor: Novo Nordisk A/S

Publications and helpful links

General Publications

• Lane WS, Favaro E, Rathor N, Jang HC, Kjaersgaard MIS, Oviedo A, Rose L, Senior P, Sesti G, Soto Gonzalez A, Franek E. A Randomized Trial Evaluating the Efficacy and Safety of Fast-Acting Insulin Aspart Compared With Insulin Aspart, Both in Combination With Insulin Degludec With or Without Metformin, in Adults With Type 2 Diabetes (ONSET 9). Diabetes Care. 2020 Aug;43(8):1710-1716. doi: 10.2337/dc19-2232. Epub 2020 Mar 24.
• Lane W, Favaro E, Jódar E, Kelkar P, Oviedo A, Sivarathinasami R, Senior PA, Sesti G, Franek E. Effective Overall Glycaemic Control with Fast-Acting Insulin Aspart Across Patients with Different Baseline Characteristics: A Post Hoc Analysis of the Onset 9 Trial. Diabetes Ther. 2022 Apr;13(4):761-774. doi: 10.1007/s13300-022-01213-3. Epub 2022 Mar 15.

Study record dates

Study Major Dates

• Study Start (Actual): September 19, 2017
• Primary Completion (Actual): January 7, 2019
• Study Completion (Actual): January 29, 2019

Study Registration Dates

• First Submitted: August 29, 2017
• First Submitted That Met QC Criteria: August 29, 2017
• First Posted (Actual): August 31, 2017

Study Record Updates

• Last Update Posted (Actual): January 11, 2022
• Last Update Submitted That Met QC Criteria: January 6, 2022
• Last Verified: January 1, 2022

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; Insulin; Insulin, Globin Zinc; Insulin Aspart; Insulin, Long-Acting; Insulin degludec, insulin aspart drug combination; Metformin
• Other Study ID Numbers: NN1218-4113; U1111-1180-0636 (Other Identifier: World Health Organization (WHO)); 2016-000878-38 (Registry Identifier: European Medicines Agency (EudraCT))

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes
• IPD Plan Description: According to the Novo Nordisk disclosure commitment on novonordisk-trials.com

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No