NCT03951805

A Research Study to Compare Two Types of Insulin: Insulin 287 and Insulin Glargine in People With Type 2 Diabetes Who Have Not Used Insulin Before

Completed Phase 2 Results posted Last updated 5 April 2021

What this trial tests

Phase 2 trial testing Insulin icodec in Diabetes Mellitus, Type 2 in 205 participants. Completed in 17 January 2020.

Timeline

9 May 2019

Primary endpoint
12 December 2019

17 January 2020

Quick facts

Lead sponsor	Novo Nordisk A/S
Phase	Phase 2
Status	Completed
Study type	INTERVENTIONAL
Allocation	randomized
Design	parallel
Masking	none
Primary purpose	treatment
Enrollment	205
Start date	9 May 2019
Primary completion	12 December 2019
Estimated completion	17 January 2020
Sites	43 locations across Slovakia, Germany, Poland, Hungary, Croatia, United States, Spain

Drugs / interventions tested

• Insulin icodec — full drug profile →
• Insulin Glargine (INSULIN GLARGINE) — full drug profile →

Conditions studied

• Diabetes Mellitus, Type 2 — all drugs for Diabetes Mellitus, Type 2 →

Sponsor

Novo Nordisk A/S — full company profile →

Who can join

Adults 18 to 75, any sex, with Diabetes Mellitus, Type 2. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Percentage of Time in Target Range (TIR) 3.9-10.0 Millimoles Per Liter (mmol/L) (70-180 Milligrams Per Deciliter (mg/dL) Measured Using CGM (Continuous Glucose Monitoring) Primary · During the last 2 weeks of treatment (week 15 and 16)

The percentage of time spent in glycaemic target range was calculated as 100 times the number of recorded measurements in glycaemic target range 3.9-10.0 mmol/L (70-180 mg/dL), both inclusive divided by the total number of recorded measurements. The endpoint was evaluated based on the data from the on-treatment without rescue medication observation period, which was the time period when a participant was considered exposed to trial product, excluding any period after initiation of a non-randomised insulin treatment (rescue medication). The endpoint is based on data recorded by CGM system. It w

Group	Value	95% CI
Insulin 287 (Titration Algorithm A)	76.65	± 1.81
Insulin 287 (Titration Algorithm B)	82.97	± 1.80
Insulin 287 (Titration Algorithm C)	80.89	± 1.81
Insulin Glargine (Titration Algorithm D)	75.89	± 1.82

Change in HbA1c (Glycated Haemoglobin) Secondary · From baseline week 0 (visit 2) to week 16 (visit 18)

Estimated mean change in HbA1c from baseline (week 0, visit 2) to end of treatment (week 16, visit 18) is presented. The endpoint was evaluated based on the data from the on-treatment without rescue medication observation period, which was the time period when a participant was considered exposed to trial product, excluding any period after initiation of a non-randomised insulin treatment (rescue medication).

Group	Value	95% CI
Insulin 287 (Titration Algorithm A)	-1.00	± 0.08
Insulin 287 (Titration Algorithm B)	-1.22	± 0.08
Insulin 287 (Titration Algorithm C)	-1.38	± 0.08
Insulin Glargine (Titration Algorithm D)	-1.02	± 0.08

Change in Fasting Plasma Glucose (FPG) Secondary · From baseline week 0 (visit 2) to week 16 (visit 18)

Estimated mean change in FPG from baseline (week 0, visit 2) to end of treatment (week 16, visit 18) is presented. The endpoint was evaluated based on the data from the on-treatment without rescue medication observation period, which was the time period when a participant was considered exposed to trial product, excluding any period after initiation of a non-randomised insulin treatment (rescue medication).

Group	Value	95% CI
Insulin 287 (Titration Algorithm A)	-2.23	± 0.17
Insulin 287 (Titration Algorithm B)	-2.42	± 0.17
Insulin 287 (Titration Algorithm C)	-3.01	± 0.17
Insulin Glargine (Titration Algorithm D)	-2.34	± 0.17

Change in Body Weight Secondary · From baseline week 0 (visit 2) to week 16 (visit 18)

Estimated mean change in body weight from baseline (week 0, visit 2) to end of treatment (week 16, visit 18) is presented. The endpoint was evaluated based on the data from the on-treatment without rescue medication observation period, which was the time period when a participant was considered exposed to trial product, excluding any period after initiation of a non-randomised insulin treatment (rescue medication).

Group	Value	95% CI
Insulin 287 (Titration Algorithm A)	0.87	± 0.35
Insulin 287 (Titration Algorithm B)	1.11	± 0.35
Insulin 287 (Titration Algorithm C)	1.25	± 0.35
Insulin Glargine (Titration Algorithm D)	0.63	± 0.35

Weekly Insulin Dose Secondary · During the last 2 weeks of treatment (week 15 and 16)

Estimated mean average weekly insulin dose during the last 2 weeks of treatment is presented. The endpoint was evaluated based on the data from the on-treatment without rescue medication observation period, which was the time period when a participant was considered exposed to trial product, excluding any period after initiation of a non-randomised insulin treatment (rescue medication).

Group	Value	95% CI
Insulin 287 (Titration Algorithm A)	142.47	119.78 – 169.45
Insulin 287 (Titration Algorithm B)	176.38	148.30 – 209.78
Insulin 287 (Titration Algorithm C)	208.90	175.94 – 248.04
Insulin Glargine (Titration Algorithm D)	145.56	122.38 – 173.12

Number of Treatment Emergent Adverse Events (TEAEs) Secondary · From baseline week 0 (visit 2) to week 21 (visit 20)

A TEAE was defined as an event that had onset date (or increase in severity) during the on-treatment observation period. The on-treatment observation period was the time period from first dose of trial product (week 0, visit 2) until the follow-up visit (week 21, visit 20) or the last date on trial product + 5 weeks for once daily insulin and +6 weeks for once weekly insulin.

Group	Value	95% CI
Insulin 287 (Titration Algorithm A)	44
Insulin 287 (Titration Algorithm B)	67
Insulin 287 (Titration Algorithm C)	58
Insulin Glargine (Titration Algorithm D)	45

Number of Severe Hypoglycaemic Episodes (Level 3) Secondary · From baseline week 0 (visit 2) to week 16 (visit 18)

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 baseline (week 0, visit 2) to end of treatment (week 16, visit 18) are presented.

Group	Value	95% CI
Insulin 287 (Titration Algorithm A)	0
Insulin 287 (Titration Algorithm B)	0
Insulin 287 (Titration Algorithm C)	0
Insulin Glargine (Titration Algorithm D)	0

Number of Clinically Significant Hypoglycaemic Episodes (Level 2) (Below 3.0 mmol/L (54 Milligrams Per Deciliter [mg/dL]), Confirmed by Blood Glucose (BG) Meter) or Severe Hypoglycaemic Episodes (Level 3) Secondary · From baseline week 0 (visit 2) to week 16 (visit 18)

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 occured from baseline (week 0, visit 2) to end of tre

Group	Value	95% CI
Insulin 287 (Titration Algorithm A)	1
Insulin 287 (Titration Algorithm B)	2
Insulin 287 (Titration Algorithm C)	8
Insulin Glargine (Titration Algorithm D)	0

Number of Hypoglycaemic Alert Episodes (Level 1) (Greater Than or Equal to 3.0 and Below 3.9 mmol/L (Greater Than or Equal to 54 and Below 70 mg/dL), Confirmed by Blood Glucose (BG) Meter) Secondary · From baseline week 0 (visit 2) to week 16 (visit 18)

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 \< 3.9 mmol/L (\>= 54 and \< 70 mg/dL) confirmed by BG meter. Number of hypoglycaemic alert episodes (level 1) that occured from baseline (week 0, visit 2) to end of treatment (week 16, visit 18) are presented.

Group	Value	95% CI
Insulin 287 (Titration Algorithm A)	14
Insulin 287 (Titration Algorithm B)	20
Insulin 287 (Titration Algorithm C)	110
Insulin Glargine (Titration Algorithm D)	10

Adverse events — posted to ClinicalTrials.gov

Time frame: From baseline (week 0) to week 21 Results are based on the safety analysis set which included all participants exposed to at least one dose of trial product.. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Insulin 287 (Titration Algorithm A)

Serious: 3/51 (6%)

Deaths: 0/51

Insulin 287 (Titration Algorithm B)

Serious: 1/51 (2%)

Deaths: 0/51

Insulin 287 (Titration Algorithm C)

Serious: 0/52 (0%)

Deaths: 0/52

Insulin Glargine (Titration Algorithm D)

Serious: 2/51 (4%)

Deaths: 0/51

Serious adverse events (7 terms)

Reaction	System	Insulin 287 (Titration Alg…	Insulin 287 (Titration Alg…	Insulin 287 (Titration Alg…	Insulin Glargine (Titratio…
Angina pectoris	Cardiac disorders	—	—	—	—
Choroid neoplasm	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—	—	—
Erysipelas	Infections and infestations	—	—	—	—
Knee arthroplasty	Surgical and medical procedures	—	—	—	—
Metastasis	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—	—	—
Pneumonia	Infections and infestations	—	—	—	—
Transitional cell carcinoma	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	—	—	—	—

Other adverse events (3 terms — click to expand)

Reaction	System	Insulin 287 (Titration Alg…	Insulin 287 (Titration Alg…	Insulin 287 (Titration Alg…	Insulin Glargine (Titratio…
Nasopharyngitis	Infections and infestations	—	—	—	—
Back pain	Musculoskeletal and connective tissue disorders	—	—	—	—
Headache	Nervous system disorders	—	—	—	—

Most-reported serious reactions: Angina pectoris, Choroid neoplasm, Erysipelas, Knee arthroplasty, Metastasis, Pneumonia, Transitional cell carcinoma.

Data from ClinicalTrials.gov NCT03951805 adverse events section.

Sponsor's own description

This study compares insulin 287 (a possible new medicine) to insulin glargine (a medicine doctors can already prescribe) in people with type 2 diabetes. Different ways of changing the dose of insulin 287 are also compared. This is done to find the best way to change the dose of insulin 287. Participants will either get insulin 287 that they will have to inject once a week or insulin glargine that participants will have to inject once a day. Which treatment participants get is decided by chance. The study will last for about 5 months (23 weeks). Participants will have 14 clinic visits and 6 phone calls with the study doctor. At 3 of the clinic visits participants will be asked not to eat or drink anything (except for water) in the last 8 hours before the visit. During the study, the study doctor will ask participants to:

* measure blood sugar every day with a blood sugar meter using a finger prick.
* write down different information in a diary daily and return this to the study doctor.
* wear a medical device (sensor) that measure blood sugar all the time for 18 weeks (about 4 months) during the study.

Women cannot take part if pregnant, breastfeeding or plan to become pregnant during the study period.

Publications & conference data

8 peer-reviewed publications reference this trial (live from Europe PMC):

1. Switching to Once-Weekly Insulin Icodec Versus Once-Daily Insulin Glargine U100 in Type 2 Diabetes Inadequately Controlled on Daily Basal Insulin: A Phase 2 Randomized Controlled Trial.
   Bajaj HS, Bergenstal RM, Christoffersen A, Davies MJ, et al · · 2021 · cited 85× · PMID 33875485 · DOI 10.2337/dc20-2877
2. A Randomized, Open-Label Comparison of Once-Weekly Insulin Icodec Titration Strategies Versus Once-Daily Insulin Glargine U100.
   Lingvay I, Buse JB, Franek E, Hansen MV, et al · · 2021 · cited 61× · PMID 33875484 · DOI 10.2337/dc20-2878
3. 57^th EASD Annual Meeting of the European Association for the Study of Diabetes.
   · 2021 · cited 11× · PMID 34468792 · DOI 10.1007/s00125-021-05519-y
4. 56^th EASD Annual Meeting of the European Association for the Study of Diabetes : 21-25 September 2020.
   · 2020 · cited 9× · PMID 32840677 · DOI 10.1007/s00125-020-05221-5
5. Once-Weekly Insulin Icodec in Diabetes Mellitus: A Systematic Review and Meta-Analysis of Randomized Clinical Trials (ONWARDS Clinical Program).
   Lisco G, De Tullio A, De Geronimo V, Giagulli VA, et al · · 2024 · cited 5× · PMID 39200316 · DOI 10.3390/biomedicines12081852
6. Emerging perspectives on once-weekly insulins in type 1 and type 2 diabetes: a mini-review.
   Denimal D. · · 2025 · cited 1× · PMID 40937414 · DOI 10.3389/fendo.2025.1656884
7. Once-weekly insulin icodec vs. daily insulin glargine in type 2 diabetes: a meta-analysis with longitudinal insights.
   Ashraf T, Kumar A, Tara A, Memon N, et al · · 2025 · PMID 40852006 · DOI 10.1097/ms9.0000000000003392
8. Abstract 3: CGM-derived parameters for once-weekly insulin icodec versus once-daily insulin glargine U100 in insulin-Naïve patients with T2D
   · 2022