Diabetes Mellitus, Type 2Phase 2NCT03751657
A Research Study to Compare Insulin 287 Once a Week to Insulin Glargine (100 Units/mL) Once a Day in People With Type 2 Diabetes.
A Phase 2 study testing Insulin icodec, Metformin and Dipeptidyl peptidase-4 inhibitors in people with Diabetes Mellitus, Type 2, run by Novo Nordisk A/S at 49 sites in 7 countries.
Trial summary
The study compares 2 medicines for people with type 2 diabetes: insulin 287 (a new medicine) and insulin glargine (a medicine doctors can already prescribe). The study doctors will test insulin 287 to see how well it works compared to insulin glargine. The study will also test if insulin 287 is safe. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Diabetes Mellitus, Type 2
- What is being tested?
- Insulin icodec, Metformin and Dipeptidyl peptidase-4 inhibitors
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 247 participants
- Where
- 49 sitesin 7 countries
- Study dates
- 29 Nov 2018to 17 Jan 2020
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Male or female, aged 18-75 years (both inclusive) at the time of signing informed consent
- Diagnosed with type 2 diabetes mellitus greater than or equal to 180 days prior to the day of screening
- HbA1c of 7.0-9.5% (53-80 mmol/mol) (both inclusive) as assessed by central laboratory
- Stable daily dose(s) for 90 days prior to the day of screening of any of the following antidiabetic drug(s) or combination regime(s): Any metformin formulations greater than or equal to 1500 mg or maximum tolerated or effective dose (as documented in subject's medical record) OR Any metformin formulations greater than or equal to 1500 mg or maximum tolerated or effective dose (as documented in subject medical record) with Dipeptidyl peptidase-4 inhibitor (DPP4i) (greater than or equal to half of the maximum approved dose according to local label or maximum tolerated or effective dose (as documented in subject's medical records)
- Insulin naïve. However, short term insulin treatment for a maximum of 14 days prior to the day of screening is allowed, as is prior insulin treatment for gestational diabetes
- Body mass index (BMI) less than or equal to 40.0 kg/m^2
Who cannot join
- Any episodes of diabetic ketoacidosis within the past 90 days prior to the day of screening and between screening and randomisation
- Myocardial infarction, stroke, hospitalisation for unstable angina pectoris or transient ischaemic attack within 180 days prior to the day of screening and between screening and randomisation
- Presently classified as being in New York Heart Association (NYHA) Class IV
- Treatment with any medication for the indication of diabetes or obesity other than stated in the inclusion criteria within the past 90 days prior to the day of screening. However, short term insulin treatment for a maximum of 14 days prior to the day of screening is allowed, as is prior insulin treatment for gestational diabetes
- 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)
- Uncontrolled and potentially unstable diabetic retinopathy or maculopathy. Verified by a pharmacologically pupil-dilated fundus examination performed by an ophthalmologist or another suitably qualified health care provider within the past 90 days prior to screening or in the period between screening and randomisation
Trial locations and contacts
49 sites in 7 countries.
49 sites in 7 countries
United States14 sites
Novo Nordisk Investigational Site
Austin, Texas, 78731
Novo Nordisk Investigational Site
Charlotte, North Carolina, 28277
Novo Nordisk Investigational Site
Chattanooga, Tennessee, 37404
Novo Nordisk Investigational Site
Chattanooga, Tennessee, 37411
Novo Nordisk Investigational Site
Dallas, Texas, 75230
Novo Nordisk Investigational Site
Dallas, Texas, 75390-9302
Novo Nordisk Investigational Site
Lancaster, California, 93534
Novo Nordisk Investigational Site
Las Vegas, Nevada, 89128
Novo Nordisk Investigational Site
Lexington, Kentucky, 40503
Novo Nordisk Investigational Site
Renton, Washington, 98057
Novo Nordisk Investigational Site
Roswell, Georgia, 30076
Novo Nordisk Investigational Site
Ventura, California, 93003
Novo Nordisk Investigational Site
Walnut Creek, California, 94598
Novo Nordisk Investigational Site
Whiteville, North Carolina, 28472
Czechia9 sites
Novo Nordisk Investigational Site
Brno, 62500
Novo Nordisk Investigational Site
Pardubice, 530 02
Novo Nordisk Investigational Site
Prague, 110 00
Novo Nordisk Investigational Site
Prague, 128 08
Novo Nordisk Investigational Site
Prague, 149 00
Novo Nordisk Investigational Site
Prague, 150 00
Novo Nordisk Investigational Site
Prague, 181 00
Novo Nordisk Investigational Site
Rakovník, 269 01
Novo Nordisk Investigational Site
Slaný, 27401
Canada7 sites
Novo Nordisk Investigational Site
Brampton, Ontario, L6S 0C6
Novo Nordisk Investigational Site
Concord, Ontario, L4K 4M2
Novo Nordisk Investigational Site
Etobicoke, Ontario, M9R 4E1
Novo Nordisk Investigational Site
Halifax, Nova Scotia, B3H 1V7
Novo Nordisk Investigational Site
Hamilton, Ontario, L8M 1K7
Novo Nordisk Investigational Site
Saint-Marc-des-Carrieres, Quebec, G0A 4B0
Novo Nordisk Investigational Site
Sarnia, Ontario, N7T 4X3
Poland6 sites
Novo Nordisk Investigational Site
Bialystok, 15-404
Novo Nordisk Investigational Site
Gdansk, 80-546
Novo Nordisk Investigational Site
Lodz, 90-132
Novo Nordisk Investigational Site
Poznan, 61-251
Novo Nordisk Investigational Site
Warsaw, 00-465
Novo Nordisk Investigational Site
Wierzchosławice, 33-122
Slovakia6 sites
Novo Nordisk Investigational Site
Bratislava, 821 02
Novo Nordisk Investigational Site
Bratislava, 851 01
Novo Nordisk Investigational Site
Košice, 040 01
Novo Nordisk Investigational Site
Moldava nad Bodvou, 045 01
Novo Nordisk Investigational Site
Šahy, 93601
Novo Nordisk Investigational Site
Trenčín, 91101
Greece5 sites
Novo Nordisk Investigational Site
Athens, 115 25
Novo Nordisk Investigational Site
Athens, GR-11527
Novo Nordisk Investigational Site
Thessaloniki, GR-54636
Novo Nordisk Investigational Site
Thessaloniki, GR-54642
Novo Nordisk Investigational Site
Thessaloniki, GR-57010
Slovenia2 sites
Novo Nordisk Investigational Site
Koper, SI-6000
Novo Nordisk Investigational Site
Ljubljana, SI-1000
About this study
Official title: An Investigational Trial Comparing the Efficacy and Safety of Once Weekly NNC0148-0287 C (Insulin 287) Versus Once Daily Insulin Glargine, Both in Combination With Metformin, With or Without DPP-4 Inhibitors, in Insulin naïve Subjects With Type 2 Diabetes Mellitus
The study compares 2 medicines for people with type 2 diabetes: insulin 287 (a new medicine) and insulin glargine (a medicine doctors can already prescribe). The study doctors will test insulin 287 to see how well it works compared to insulin glargine. The study will also test if insulin 287 is safe. The study participants will either get insulin 287 or insulin glargine (100 units/mL) - which treatment the participants get is decided by chance. The participants will need to inject their selves every day about the same time. Once a week the participant will need to take 1 extra injection on the same day of the week. The participants will have 16 clinic visits and 14 phone calls with the study doctor. During the study, the doctors will ask you to: 1) measure your blood sugar every day with a blood glucose meter using a finger prick, 2) write down different information in a paper diary daily and return this to your doctor, 3) wear a medical device to measure your blood sugar all the time for 2 weeks 5 times during the study.
- Conditions
- Diabetes Mellitus, Type 2
- Being tested
- Insulin icodec, Placebo (insulin 287), Metformin, Dipeptidyl peptidase-4 inhibitors, Insulin glargine
- Medical subject headings
- Diabetes Mellitus, Type 2
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Insulin icodecDrug
Also called Insulin 287
Insulin 287 once weekly subcutaneous (s.c.) injections at the starting dose of 70 units. Dose adjustment was done for the individual patient based on the three pre-breakfast self-measured plasma glucose values measured on two days prior to titration and on the day of the contact. The insulin dose adjustment should aim to reach an SMPG of 3.9-6.0 mmol/L (70-108 mg/dL)
Placebo (insulin 287)Drug
Participants will receive once weekly s.c. injections of placebo equivalent to insulin 287.
MetforminDrug
Metformin is considered as non investigational medicinal product. Subject will continue metformin at stable pre-trial dose.
Dipeptidyl peptidase-4 inhibitorsDrug
Dipeptidyl peptidase-4 inhibitors are considered as non investigational medicinal products. Subject will continue dipeptidyl peptidase-4 inhibitor at stable pre-trial dose.
Insulin glargineDrug
Insulin glargine (100 U/mL) once daily s.c. injections at the starting dose of 10 units. Dose adjustment will be done for the individual patient based on the three pre-breakfast self-measured plasma glucose values measured on two days prior to titration and on the day of the contact. The insulin dose adjustment should aim to reach an SMPG of 3.9-6.0 mmol/L (70-108 mg/dL).
Placebo (insulin glargine)Drug
Participants will receive once daily s.c. injections of placebo equivalent to insulin glargine.
| Study group | Role | What they receive |
|---|---|---|
| Insulin 287 | Experimental | Participants will receive once weekly insulin 287 and once daily placebo in combination with metformin with or without dipeptidyl peptidase-4 inhibitors (DPP4i) during 26 weeks of treatment period. Receives: Drug: Insulin icodec; Drug: Metformin; Drug: Dipeptidyl peptidase-4 inhibitors; Drug: Placebo (insulin glargine) |
| Insulin glargine | Active comparator | Participants will receive once daily insulin glargine and once weekly placebo in combination with metformin with or without DPP4i during 26 weeks of treatment period. Receives: Drug: Placebo (insulin 287); Drug: Metformin; Drug: Dipeptidyl peptidase-4 inhibitors; Drug: Insulin glargine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Change in Glycated Haemoglobin (HbA1c) [Percentage Point (%-Point)]
Change in HbA1c from baseline (week 0) to week 26 is presented. The endpoint was evaluated based on the data from on-treatment without ancillary treatment period, starting at the date of first dose of trial product until the follow-up visit, or the last date on trial product + 5 weeks for once daily insulin and + 6 weeks for once weekly insulin, or initiation of any diabetes treatment other than trial products and metformin +/- DPP4i, or increase of the dose of metformin or DPP4i.
Measured: From baseline (Visit 2) to week 26 (Visit 28)
Change in HbA1c [Millimoles/Mole (mmol/Mol)]
Change in HbA1c from baseline (week 0) to week 26 is presented. The endpoint was evaluated based on the data from on-treatment without ancillary treatment period, starting at the date of first dose of trial product until the follow-up visit, or the last date on trial product + 5 weeks for once daily insulin and + 6 weeks for once weekly insulin, or initiation of any diabetes treatment other than trial products and metformin +/- DPP4i, or increase of the dose of metformin or DPP4i.
Measured: From baseline (Visit 2) to week 26 (Visit 28)
Secondary outcomes (14)
Change in Fasting Plasma Glucose
Change in fasting plasma glucose from baseline (week 0) to week 26 is presented. The endpoint was evaluated based on the data from on-treatment without ancillary treatment period, starting at the date of first dose of trial product until the follow-up visit, or the last date on trial product + 5 weeks for once daily insulin and + 6 weeks for once weekly insulin, or initiation of any diabetes treatment other than trial products and metformin +/- DPP4i, or increase of the dose of metformin or DPP4i.
Measured: From baseline (Visit 2) to week 26 (Visit 28)
9-point Profile (Individual SMPG Values)
Participants measured their plasma glucose (PG) levels using blood glucose meters (as plasma equivalent values of capillary whole blood glucose) at 9 time points (before breakfast, 90 minutes after the start of breakfast, before lunch, 90 minutes after the start of lunch, before dinner, 90 minutes after the start of dinner, at bedtime, at 4 am, before breakfast the following day). 9-point SMPG values after 26 weeks are presented. The endpoint was evaluated based on the data from on-treatment without ancillary treatment period, starting at the date of first dose of trial product until the follow-up visit, or the last date on trial product + 5 weeks for once daily insulin and + 6 weeks for once weekly insulin, or initiation of any diabetes treatment other than trial products and metformin +/- DPP4i, or increase of the dose of metformin or DPP4i.
Measured: Week 26 (Visit 28)
Change in Mean of the 9-point Profile, Defined as the Area Under the Profile Divided by Measurement Time
Participants measured their PG levels using blood glucose meters at 9 time points (before breakfast, 90 minutes after the start of breakfast, before lunch, 90 minutes after the start of lunch, before dinner, 90 minutes after the start of dinner, at bedtime, at 4 am, before breakfast the following day). The endpoint was evaluated based on the data from on-treatment without ancillary treatment period, starting at the date of first dose of trial product until the follow-up visit, or the last date on trial product + 5 weeks for once daily insulin and + 6 weeks for once weekly insulin, or initiation of any diabetes treatment other than trial products and metformin +/- DPP4i, or increase of the dose of metformin or DPP4i.
Measured: From baseline (Visit 2) to week 26 (Visit 28)
Fluctuations of the 9-point Profile (Defined as the Integrated Absolute Distance From the Mean Profile Value Divided by Measurement Time).
Participants measured their plasma glucose (PG) levels using blood glucose meters at 9 time points (before breakfast, 90 minutes after the start of breakfast, before lunch, 90 minutes after the start of lunch, before dinner, 90 minutes after the start of dinner, at bedtime, at 4 am, before breakfast the following day). Presented fluctuation in 9-point SMPG profile is the integrated absolute distance from the mean profile value divided by measurement time and is calculated using the trapezoidal method. The endpoint was evaluated based on the data from on-treatment without ancillary treatment period, starting at the date of first dose of trial product until the follow-up visit, or the last date on trial product + 5 weeks for once daily insulin and + 6 weeks for once weekly insulin, or initiation of any diabetes treatment other than trial products and metformin +/- DPP4i, or increase of the dose of metformin or DPP4i.
Measured: Week 26 (Visit 28)
Fasting C-peptide
Fasting C-peptide at week 26 is presented. The endpoint was evaluated based on the data from on-treatment without ancillary treatment period, starting at the date of first dose of trial product until the follow-up visit, or the last date on trial product + 5 weeks for once daily insulin and + 6 weeks for once weekly insulin, or initiation of any diabetes treatment other than trial products and metformin +/- DPP4i, or increase of the dose of metformin or DPP4i.
Measured: At week 26 (Visit 28)
Change in Body Weight
Change in body weight from baseline (week 0) to week 26 is presented. The endpoint was evaluated based on the data from on-treatment without ancillary treatment period, starting at the date of first dose of trial product until the follow-up visit, or the last date on trial product + 5 weeks for once daily insulin and + 6 weeks for once weekly insulin, or initiation of any diabetes treatment other than trial products and metformin +/- DPP4i, or increase of the dose of metformin or DPP4i.
Measured: From baseline (Visit 2) to week 26 (Visit 28)
Weekly Dose of Insulin 287 and Weekly Dose of Insulin Glargine
Weekly dose of insulin 287 and weekly dose of glargine at week 25 and week 26 are presented.The endpoint was evaluated based on the data from on-treatment without ancillary treatment period, starting at the date of first dose of trial product until the follow-up visit, or the last date on trial product + 5 weeks for once daily insulin and + 6 weeks for once weekly insulin, or initiation of any diabetes treatment other than trial products and metformin +/- DPP4i, or increase of the dose of metformin or DPP4i.
Measured: week 25 (Visit 27) and 26 (Visit 28)
Number of Treatment Emergent Adverse Events (TEAEs)
An adverse event (AE) is any untoward medical occurrence in a clinical trial subject administered or using a medicinal product, whether or not considered related to the medicinal product or usage. A TEAE was defined as an event that had onset date (or increase in severity) during the on-treatment observation period. The endpoint was evaluated based on the data from on-treatment period, starting at the date of first dose of trial product, and ending at follow-up visit, or the last date on trial product + 5 weeks for once daily insulin and + 6 weeks for once weekly insulin.
Measured: From baseline (Visit 2) to week 31 (Visit 30)
Number of Hypoglycaemic Alert Episodes (Level 1) (≥3.0 and <3.9 mmol/L (≥54 and <70 mg/dL), Confirmed by BG Meter)
Hypoglycaemia alert value (level 1) was defined as episodes that were sufficiently low for treatment with fast-acting carbohydrate and dose adjustment of glucose-lowering therapy with plasma glucose value of equal to or above (>=) 3.0 and less than (<) 3.9 mmol/L (>= 54 and < 70 mg/dL) confirmed by BG meter. Number of hypoglycaemic alert episodes (level 1) that occurred from week 0 to week 26 are presented.
Measured: From baseline (Visit 2) to week 26 (Visit 28)
Number of Clinically Significant Hypoglycaemic Episodes (Level 2) (<3.0 mmol/L (54 mg/dL), Confirmed by BG Meter) or Severe Hypoglycaemic Episodes (Level 3)
Clinically significant hypoglycaemic episodes (level 2) were defined as episodes that were sufficiently low to indicate serious, clinically important hypoglycaemia with plasma glucose value of less than (<) 3.0 mmol/L (54 mg/dL). Severe hypoglycaemic episodes (level 3) were defined as episodes that were associated with severe cognitive impairment requiring external assistance for recovery. Number of clinically significant hypoglycaemic episodes (level 2), confirmed by blood glucose (BG) meter or severe hypoglycaemic episodes (level 3) that occurred from week 0 to week 26 are presented.
Measured: From baseline (Visit 2) to week 26 (Visit 28)
Number of Severe Hypoglycaemic Episodes (Level 3)
Severe hypoglycaemic episodes (level 3) were defined as episodes that were associated with severe cognitive impairment requiring external assistance for recovery. Number of severe hypoglycaemic episodes that occurred from week 0 to week 26 are presented.
Measured: From baseline (Visit 2) to week 26 (Visit 28)
Change in Anti-insulin 287 Antibody Titres
Samples from the insulin 287 arm of the study were analysed for anti-insulin 287 antibodies. Confirmed anti-insulin 287 antibody positive samples had an antibody titre value determined. The endpoint was evaluated based on the data from in-trial period, starting at randomisation, and ending at the last direct participant-site contact, or when participant withdrew their informed consent, or the last participant-investigator contact for participants lost to follow-up, or death.
Measured: From baseline (Visit 2) to week 31 (Visit 30)
Change in Cross-reactive Anti-human Insulin Antibody Status (Positive/Negative)
Anti-insulin 287 or glargine antibodies were classified as negative if % B/T was below a certain cut point. Samples positive for anti-insulin 287 or glargine antibodies were further tested for cross-reactivity to endogenous insulin. Samples not further tested are categorised as not applicable (NA). Unknown refers to samples with insufficient volume to perform analysis. The endpoint was evaluated based on the data from in-trial period, starting at randomisation, and ending at the last direct participant-site contact, or when participant withdrew their informed consent, or the last participant-investigator contact for participants lost to follow-up, or death.
Measured: From baseline (Visit 2) to week 31 (Visit 30)
Change in Anti-insulin 287 Antibody Level
Change in anti-insulin 287 antibodies level is not assessed because change in anti-insulin 287 antibody titres is a more meaningful way of describing the change in antibody levels. The results for change in anti-insulin 287 antibody titres are reported as a separate endpoint.
Measured: From baseline (Visit 2) to week 31 (Visit 30)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 Nov 2018
- Study start29 Nov 2018
- Primary completion16 Dec 2019
- Study completion17 Jan 2020
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Diabetes Mellitus, Type 2Studies of the same condition, open and under way.
- More trials run by Novo Nordisk A/SThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 247 participants (actual)
Sponsor and investigators
- Lead sponsor
- Novo Nordisk A/S
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Clinical Reporting Anchor and Disclosure (1452), Study director, Novo Nordisk A/S
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03751657
- Sponsor's protocol ID
- NN1436-4383
- Other IDs
- U1111-1208-4124, 2018-000322-63, 2018
- Status last verified
- Mar 2021
- First submitted
- 16 Nov 2018
- Last updated
- 2 Apr 2021
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: According to the Novo Nordisk disclosure commitment on novonordisk-trials.com
Publications
Rosenstock J, Bajaj HS, Janež A, Silver R, Begtrup K, Hansen MV, Jia T, Goldenberg R. Once-Weekly Insulin for Type 2 Diabetes without Previous Insulin Treatment. PMID:32960514
Kristensen NR, Haridas MP, Philis-Tsimikas A, Ribel-Madsen R, Mathieu C. The Effect of Intrinsic Factors on the Pharmacokinetics of Once-Weekly Insulin Icodec in Type 1 and Type 2 Diabetes: A Population Pharmacokinetic Analysis of Phase II and Phase III trials. Clin Pharmacokinet. 2026 Sep 30. doi: 10.1007/s40262-026-01710-9. Online ahead of print.
PubMed 42814374Rosenstock J, Bajaj HS, Janez A, Silver R, Begtrup K, Hansen MV, Jia T, Goldenberg R; NN1436-4383 Investigators. Once-Weekly Insulin for Type 2 Diabetes without Previous Insulin Treatment. N Engl J Med. 2020 Nov 26;383(22):2107-2116. doi: 10.1056/NEJMoa2022474. Epub 2020 Sep 22.
PubMed 32960514
Study at a glance
From the registry record, last updated by the sponsor on 2 Apr 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Investigational Trial Comparing the Efficacy and Safety of Once Weekly NNC0148-0287 C (Insulin 287) Versus Once Daily Insulin Glargine, Both in Combination With Metformin, With or Without DPP-4 Inhibitors, in Insulin naïve Subjects With Type 2 Diabetes Mellitus
- ClinicalTrials.gov ID
- NCT03751657
- Acronym / sponsor ID
- NN1436-4383
- Conditions
- Diabetes Mellitus, Type 2
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 247 participants (actual)
- Lead sponsor
- Novo Nordisk A/SIndustry (pharma, biotech, devices)
- Study start
- 29 Nov 2018 (actual)
- Primary completion
- 16 Dec 2019 (actual)
- Study completion
- 17 Jan 2020 (actual)
- First posted
- 23 Nov 2018 (actual)
- Results
- Posted 1 Feb 2021
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The study compares 2 medicines for people with type 2 diabetes: insulin 287 (a new medicine) and insulin glargine (a medicine doctors can already prescribe). The study doctors will test insulin 287 to see how well it works compared to insulin glargine. The study will also test if insulin 287 is safe. The study participants will either get insulin 287 or insulin glargine (100 units/mL) - which treatment the participants get is decided by chance. The participants will need to inject their selves every day about the same time. Once a week the participant will need to take 1 extra injection on the same day of the week. The participants will have 16 clinic visits and 14 phone calls with the study doctor. During the study, the doctors will ask you to: 1) measure your blood sugar every day with a blood glucose meter using a finger prick, 2) write down different information in a paper diary daily and return this to your doctor, 3) wear a medical device to measure your blood sugar all the time for 2 weeks 5 times during the study.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Insulin 287 | Experimental | Drug: Insulin icodec, Drug: Metformin, Drug: Dipeptidyl peptidase-4 inhibitors, Drug: Placebo (insulin glargine)Participants will receive once weekly insulin 287 and once daily placebo in combination with metformin with or without dipeptidyl peptidase-4 inhibitors (DPP4i) during 26 weeks of treatment period. |
| Insulin glargine | Active comparator | Drug: Placebo (insulin 287), Drug: Metformin, Drug: Dipeptidyl peptidase-4 inhibitors, Drug: Insulin glargineParticipants will receive once daily insulin glargine and once weekly placebo in combination with metformin with or without DPP4i during 26 weeks of treatment period. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Male or female, aged 18-75 years (both inclusive) at the time of signing informed consent
- Diagnosed with type 2 diabetes mellitus greater than or equal to 180 days prior to the day of screening
- HbA1c of 7.0-9.5% (53-80 mmol/mol) (both inclusive) as assessed by central laboratory
- Stable daily dose(s) for 90 days prior to the day of screening of any of the following antidiabetic drug(s) or combination regime(s): Any metformin formulations greater than or equal to 1500 mg or maximum tolerated or effective dose (as documented in subject's medical record) OR Any metformin formulations greater than or equal to 1500 mg or maximum tolerated or effective dose (as documented in subject medical record) with Dipeptidyl peptidase-4 inhibitor (DPP4i) (greater than or equal to half of the maximum approved dose according to local label or maximum tolerated or effective dose (as documented in subject's medical records)
- Insulin naïve. However, short term insulin treatment for a maximum of 14 days prior to the day of screening is allowed, as is prior insulin treatment for gestational diabetes
Key exclusion criteria (6 listed)
- Any episodes of diabetic ketoacidosis within the past 90 days prior to the day of screening and between screening and randomisation
- Myocardial infarction, stroke, hospitalisation for unstable angina pectoris or transient ischaemic attack within 180 days prior to the day of screening and between screening and randomisation
- Presently classified as being in New York Heart Association (NYHA) Class IV
- Treatment with any medication for the indication of diabetes or obesity other than stated in the inclusion criteria within the past 90 days prior to the day of screening. However, short term insulin treatment for a maximum of 14 days prior to the day of screening is allowed, as is prior insulin treatment for gestational diabetes
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Insulin icodecAlso: Insulin 287Insulin 287 once weekly subcutaneous (s.c.) injections at the starting dose of 70 units. Dose adjustment was done for the individual patient based on the three pre-breakfast self-measured plasma glucose values measured on two days prior to titration and on the day of the contact. The insulin dose adjustment should aim to reach an SMPG of 3.9-6.0 mmol/L (70-108 mg/dL) | Drug | Insulin 287 |
| Placebo (insulin 287)Participants will receive once weekly s.c. injections of placebo equivalent to insulin 287. | Drug | Insulin glargine |
| MetforminMetformin is considered as non investigational medicinal product. Subject will continue metformin at stable pre-trial dose. | Drug | Insulin 287, Insulin glargine |
| Dipeptidyl peptidase-4 inhibitorsDipeptidyl peptidase-4 inhibitors are considered as non investigational medicinal products. Subject will continue dipeptidyl peptidase-4 inhibitor at stable pre-trial dose. | Drug | Insulin 287, Insulin glargine |
| Insulin glargineInsulin glargine (100 U/mL) once daily s.c. injections at the starting dose of 10 units. Dose adjustment will be done for the individual patient based on the three pre-breakfast self-measured plasma glucose values measured on two days prior to titration and on the day of the contact. The insulin dose adjustment should aim to reach an SMPG of 3.9-6.0 mmol/L (70-108 mg/dL). | Drug | Insulin glargine |
| Placebo (insulin glargine)Participants will receive once daily s.c. injections of placebo equivalent to insulin glargine. | Drug | Insulin 287 |
Primary outcome
Change in Glycated Haemoglobin (HbA1c) [Percentage Point (%-Point)]
Time frame: From baseline (Visit 2) to week 26 (Visit 28)
Change in HbA1c from baseline (week 0) to week 26 is presented. The endpoint was evaluated based on the data from on-treatment without ancillary treatment period, starting at the date of first dose of trial product until the follow-up visit, or the last date on trial product + 5 weeks for once daily insulin and + 6 weeks for once weekly insulin, or initiation of any diabetes treatment other than trial products and metformin +/- DPP4i, or increase of the dose of metformin or DPP4i.
Change in HbA1c [Millimoles/Mole (mmol/Mol)]
Time frame: From baseline (Visit 2) to week 26 (Visit 28)
Change in HbA1c from baseline (week 0) to week 26 is presented. The endpoint was evaluated based on the data from on-treatment without ancillary treatment period, starting at the date of first dose of trial product until the follow-up visit, or the last date on trial product + 5 weeks for once daily insulin and + 6 weeks for once weekly insulin, or initiation of any diabetes treatment other than trial products and metformin +/- DPP4i, or increase of the dose of metformin or DPP4i.
14 secondary outcomes
Change in Fasting Plasma Glucose
Time frame: From baseline (Visit 2) to week 26 (Visit 28)
9-point Profile (Individual SMPG Values)
Time frame: Week 26 (Visit 28)
Change in Mean of the 9-point Profile, Defined as the Area Under the Profile Divided by Measurement Time
Time frame: From baseline (Visit 2) to week 26 (Visit 28)
Fluctuations of the 9-point Profile (Defined as the Integrated Absolute Distance From the Mean Profile Value Divided by Measurement Time).
Time frame: Week 26 (Visit 28)
Fasting C-peptide
Time frame: At week 26 (Visit 28)
Change in Body Weight
Time frame: From baseline (Visit 2) to week 26 (Visit 28)
Weekly Dose of Insulin 287 and Weekly Dose of Insulin Glargine
Time frame: week 25 (Visit 27) and 26 (Visit 28)
Number of Treatment Emergent Adverse Events (TEAEs)
Time frame: From baseline (Visit 2) to week 31 (Visit 30)
Number of Hypoglycaemic Alert Episodes (Level 1) (≥3.0 and <3.9 mmol/L (≥54 and <70 mg/dL), Confirmed by BG Meter)
Time frame: From baseline (Visit 2) to week 26 (Visit 28)
Number of Clinically Significant Hypoglycaemic Episodes (Level 2) (<3.0 mmol/L (54 mg/dL), Confirmed by BG Meter) or Severe Hypoglycaemic Episodes (Level 3)
Time frame: From baseline (Visit 2) to week 26 (Visit 28)
Number of Severe Hypoglycaemic Episodes (Level 3)
Time frame: From baseline (Visit 2) to week 26 (Visit 28)
Change in Anti-insulin 287 Antibody Titres
Time frame: From baseline (Visit 2) to week 31 (Visit 30)
Change in Cross-reactive Anti-human Insulin Antibody Status (Positive/Negative)
Time frame: From baseline (Visit 2) to week 31 (Visit 30)
Change in Anti-insulin 287 Antibody Level
Time frame: From baseline (Visit 2) to week 31 (Visit 30)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Apr 2021.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publicationRosenstock J, Bajaj HS, Janež A, Silver R, Begtrup K, Hansen MV, Jia T, Goldenberg R. Once-Weekly Insulin for Type 2 Diabetes without Previous Insulin Treatment. PMID:32960514
- Derived from this study: PubMed 42814374Kristensen NR, Haridas MP, Philis-Tsimikas A, Ribel-Madsen R, Mathieu C. The Effect of Intrinsic Factors on the Pharmacokinetics of Once-Weekly Insulin Icodec in Type 1 and Type 2 Diabetes: A Population Pharmacokinetic Analysis of Phase II and Phase III trials. Clin Pharmacokinet. 2026 Sep 30. doi: 10.1007/s40262-026-01710-9. Online ahead of print.
- Derived from this study: PubMed 32960514Rosenstock J, Bajaj HS, Janez A, Silver R, Begtrup K, Hansen MV, Jia T, Goldenberg R; NN1436-4383 Investigators. Once-Weekly Insulin for Type 2 Diabetes without Previous Insulin Treatment. N Engl J Med. 2020 Nov 26;383(22):2107-2116. doi: 10.1056/NEJMoa2022474. Epub 2020 Sep 22.
- Individual participant dataSharing planned: Yes. According to the Novo Nordisk disclosure commitment on novonordisk-trials.com
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Clinical Reporting Anchor and Disclosure (1452) study director
Novo Nordisk A/S
49 sites in 7 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Insulin icodec, Metformin and Dipeptidyl peptidase-4 inhibitors in people with Diabetes Mellitus, Type 2, run by Novo Nordisk A/S at 49 sites in 7 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 2 Apr 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 49 sites in United States, Czechia, Canada, Poland, Slovakia and 2 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 1 Feb 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Change in Glycated Haemoglobin (HbA1c) [Percentage Point (%-Point)] (time frame: From baseline (Visit 2) to week 26 (Visit 28)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03751657, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Apr 2021.