Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Label indication Awiqli is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus. Awiqli is a long-acting human insulin analog indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus ( 1 ) FDA label
Also known as Insulin 287
Insulin icodec · 24 trials · 5 indications
Measured in percentage (%)-points.
Change in HbA1c from week 0 to week 26 in percentage point is presented.
Change in HbA1c from baseline to week 26 is presented. Data is reported for 'in-trial' period. In-trial observation period started at randomisation and ended at the date of: the last direct participant-site contact; withdrawal for participants who withdrew their informed consent; the last participant-investigator contact as defined by the investigator for participants who were lost to follow-up (i.e. possibly an unscheduled phone visit); death for participants who died before any of the above.
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 was required that at least 70% of the planned CGM measurements during weeks 15-16 were available for endpoint data to be included in the analysis.
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 on treatment with trial product, excluding any period after initiation of a non-randomised insulin treatment (rescue medication).
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 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 in percentage of readings.
Measured in picomoles\*hours per liter (pmol\*h/L).
Measured in picomoles per liter (pmol/L).
Measured in hours.
pmol\*h/L
From 0 hours until infinity after trial product administration (pmol\*h/L)
pmol\*h/L
From 0 hours until infinity after trial product administration (pmol\*h/L)
Yes/No Blood sugar lower than 3.0 mmol/L (54 mg/dL) after receiving a double dose of basal insulin Number of subjects experiencing an event is to be reported
Measured in pmol\*h/L
Measured in pmol\*h/L
Measured in pmol\*h/L
| Arm | Type | Description |
|---|---|---|
| Insulin icodec + insulin aspart | EXPERIMENTAL | Participants will receive subcutaneously once weekly insulin icodec in combination with 2-4 times daily insulin aspart . |
| Insulin glargine+ insulin aspart | ACTIVE_COMPARATOR | Participants will receive subcutaneously once daily insulin glargine in combination with 2-4 times daily insulin aspart. |
| Insulin icodec | EXPERIMENTAL | Participants will receive Insulin icodec subcutaneously once weekly. |
| Insulin glargine U100 | ACTIVE_COMPARATOR | Participants will receive Insulin glargine subcutaneously once daily. |
| Insulin Icodec + Semaglutide | EXPERIMENTAL | Participants will receive insulin icodec once weekly for 26 weeks in run-in period to ensure the dose optimization. Thereafter, participants meeting intensification criteria will proceed to the 26-week treatment period to receive once weekly semaglutide subcutaneously starting from 0.25 milligrams (mg) and dose increased up to 1 mg along with 700 units per milliliter (U/mL) insulin icodec therapy. There are no maximum or minimum insulin doses. |
| Insulin glargine + insulin aspart | ACTIVE_COMPARATOR | Participants will get once daily injections in combination with 2-4 times daily injections of insulin aspart |
| Insulin degludec + insulin aspart | ACTIVE_COMPARATOR | insulin degludec once a day in combination with 2-4 times daily injections of insulin aspart at meal times. |
| Once weekly insulin icodec + once daily placebo | EXPERIMENTAL | Participants will get once daily and once weekly injections |
| Once weekly placebo and once daily insulin degludec | EXPERIMENTAL | Participants will get once daily and once weekly injections |
| Insulin icodec with DoseGuide | EXPERIMENTAL | Participants randomised to insulin icodec will use insulin icodec with the DoseGuide App to guide their titration. |
| Once daily basal insulin analogues | ACTIVE_COMPARATOR | Participants randomised to basal insulin analogue injections once daily |
| Insulin glargine | ACTIVE_COMPARATOR | Insulin glargine + non-insulin anti-diabetic drugs. The pre-trial non-insulin anti-diabetic background medication should be maintained at the stable, pre-trial dose and at the same frequency during the entire treatment period |
| Insulin 287 algorithm A | EXPERIMENTAL | Controlled on metformin with or without DPP4i (dipeptidyl peptidase-4 inhibitors) and with or without SGLT2i (sodium-glucose cotransporter 2 inhibitors). |
| Insulin 287 algorithm B | EXPERIMENTAL | Controlled on metformin with or without DPP4i and with or without SGLT2i. |
| Insulin 287 algorithm C | EXPERIMENTAL | Controlled on metformin with or without DPP4i and with or without SGLT2i. |
| Insulin Glargine algorithm D | ACTIVE_COMPARATOR | Controlled on metformin with or without DPP4i and with or without SGLT2i. |
| Insulin 287 (with 100% loading dose) | EXPERIMENTAL | Participants will receive insulin 287 injections once weekly (OW). A unit to unit switch approach with an additional 100% loading dose of insulin 287 will be used. |
| Insulin 287 (without loading dose) | EXPERIMENTAL | Participants will receive insulin 287 injections OW. A unit to unit switch approach without loading dose of insulin 287 will be used. |
| 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. |
| Participants with Type 2 Diabetes | EXPERIMENTAL | Participants will receive single subcutaneous (s.c.) fixed dose of insulin icodec (700 units per milliliter \[U/mL\]) that is 5.6 units per kilogram (U/kg) bodyweight. Subjects will be followed up for 5 weeks after dosing. |
| Subjects with normal hepatic function | EXPERIMENTAL | The participants will be allocated into four groups. Receiving one insulin icodec dose, administered subcutaneously. |
| Subjects with mild hepatic impairment, child-pugh grade A | EXPERIMENTAL | The participants will be allocated into four groups. Receiving one insulin icodec dose, administered subcutaneously. |
| Subjects with moderate hepatic impairment, child-pugh grade B | EXPERIMENTAL | The participants will be allocated into four groups. Receiving one insulin icodec dose, administered subcutaneously. |
| Subjects with severe hepatic impairment, child-pugh grade C | EXPERIMENTAL | The participants will be allocated into four groups. Receiving one insulin icodec dose, administered subcutaneously. |
| Insulin icodec treatment sequence with injection region abdomen | EXPERIMENTAL | Each subject will be randomised to one of six treatment sequences, consisting of three single-dose administrations of insulin icodec (s.c. in the abdomen, the upper arm and the thigh) in a balanced manner on three separate treatment visits. |
| Insulin icodec treatment sequence with injection region upper arm | EXPERIMENTAL | Each subject will be randomised to one of six treatment sequences, consisting of three single-dose administrations of insulin icodec (s.c. in the abdomen, the upper arm and the thigh) in a balanced manner on three separate treatment visits. |
| Insulin icodec treatment sequence with injection region thigh | EXPERIMENTAL | Each subject will be randomised to one of six treatment sequences, consisting of three single-dose administrations of insulin icodec (s.c. in the abdomen, the upper arm and the thigh) in a balanced manner on three separate treatment visits. |
| Insulin 287 followed by insulin glargine | EXPERIMENTAL | Run-in period (3 to 28 days): Once daily insulin glargine treatment with or without any usual metformin treatment. After run-in, participants will receive insulin 287 once a week (OW) for 6 weeks. After insulin 287 treatment, participants will receive insulin glargine U100 OD for 12 days. |
| Insulin glargine followed by insulin 287 | ACTIVE_COMPARATOR | Run-in period (3 to 28 days): Once daily insulin glargine treatment with or without any usual metformin treatment. After run-in, participants will receive insulin glargine U100 OD for 12 days. After insulin glargine treatment, participants will receive insulin 287 OW for 6 weeks. |
| Insulin 287 followed by insulin glargine U100 | EXPERIMENTAL | Run-in period (2 days to 7 weeks): The basal insulin glargine dose for each subject will be established and optimised. After run-in, participants will receive insulin 287 once a week (OW) for 8 weeks and subsequent 4 weeks of terminal pharmacokinetic (PK) sampling where subjects are treated with once daily (OD) insulin glargine. After insulin 287 treatment, participants will receive insulin glargine U100 OD for 2 weeks. |
| Insulin glargine U100 followed by insulin 287 | EXPERIMENTAL | Run-in period (2 days to 7 weeks): The basal insulin glargine dose for each subject will be established and optimised. After run-in, participants will receive insulin glargine U100 OD for 2 weeks followed by 1-14 days (at least 1 day is mandatory) of continued insulin glargine treatment. After insulin glargine treatment, participants will receive insulin 287 OW for 8 weeks and subsequent 4 weeks of terminal PK sampling. |
| Participants with normal renal function | EXPERIMENTAL | Participants with normal renal function (glomerular filtration rate \[GFR\] of greater than or equal to 90 ml/min) will receive single dose of insulin 287 on Day 1. |
| Participants with mildly decreased renal function | EXPERIMENTAL | Participants with mildly decreased renal function (GFR of 60 to less than 90 ml/min) will receive single dose of insulin 287 on Day 1. |
| Participants with moderately decreased renal function | EXPERIMENTAL | Participants with moderately decreased renal function (GFR of 30 to less than 60 ml/min) will receive single dose of insulin 287 on Day 1. |
| Participants with severely decreased renal function | EXPERIMENTAL | Participants with severely decreased renal function (GFR of less than 30 not requiring dialysis) will receive single dose of insulin 287 on Day 1. |
| Participants with end-stage renal disease | EXPERIMENTAL | Participants with end-stage renal disease requiring haemodialysis will receive single dose of insulin 287 on Day 1. |
| Insulin 287 + placebo | EXPERIMENTAL | Each dose group will consist of 16 subjects randomised for once-weekly s.c. (subcutaneous, under the skin) administration of insulin 287 and once daily s.c. placebo (n=12) or once-weekly s.c. placebo and once daily s.c. insulin degludec (n=4) |
| Insulin degludec + placebo | ACTIVE_COMPARATOR | Each dose group will consist of 16 subjects randomised for once-weekly s.c. (subcutaneous, under the skin) administration of insulin 287 and once daily s.c. placebo (n=12) or once-weekly s.c. placebo and once daily s.c. insulin degludec (n=4) |
| Name | Type | Description |
|---|---|---|
| Insulin icodec | DRUG | Insulin icodec will be administered as subcutaneous injection |
| Insulin glargine | DRUG | Insulin glargine will be administered as subcutaneous injection. |
| Insulin aspart | DRUG | Insulin aspart will be administered as a subcutaneous injection. |
| Semaglutide | DRUG | Participants will receive once weekly semaglutide subcutaneously starting from 0.25 mg and dose increased up to 1 mg for 26 weeks. |
| insulin degludec | DRUG | insulin degludec 100 units/mL, subcutaneously (under the skin), solution for injection once daily |
| Placebo insulin icodec | DRUG | You will get a pen for weekly injection and one for daily injection. One will be insulin degludec 100 units/mL and the other will be placebo. Subcutaneously (under the skin) injections |
| Placebo insulin degludec | DRUG | You will get a pen for weekly injection and one for daily injection. One will be icodec 700 units/mL and the other will be placebo. Subcutaneously (under the skin) injections |
| Insulin Glargine 100U/mL | DRUG | Participants will receive subcutaneous (s.c.) injections of insulin analogues once daily for 52 weeks. |
| Insulin Glargine 300U/mL | DRUG | Participants will receive subcutaneous (s.c.) injections of insulin analogues once daily for 52 weeks. |
| Insulin glargine U100 | DRUG | Participants will receive s.c. injections of insulin glargine OD for 16 weeks |
| Placebo (insulin 287) | DRUG | Participants will receive once weekly s.c. injections of placebo equivalent to insulin 287. |
| Metformin | DRUG | Metformin is considered as non investigational medicinal product. Subject will continue metformin at stable pre-trial dose. |
| Dipeptidyl peptidase-4 inhibitors | DRUG | Dipeptidyl peptidase-4 inhibitors are considered as non investigational medicinal products. Subject will continue dipeptidyl peptidase-4 inhibitor at stable pre-trial dose. |
| Placebo (insulin glargine) | DRUG | Participants will receive once daily s.c. injections of placebo equivalent to insulin glargine. |
| IGlar U100 | DRUG | Participants will receive subcutaneous injections of insulin glargine once weekly for 2 weeks. |
| placebo | DRUG | Administered once daily subcutaneously for 35 days |
Inclusion Criteria: * Diagnosed with type 1 diabetes mellitus greater than or equal to (≥) 1 year before screening. * Treated with multiple daily insulin injections (daily basal insulin analogue and bolus insulin analogue regimen) ≥ 6 months before screening. * HbA1c from 7.0-10.0 percentage (%) (5...
Insulin icodec is an investigational insulin developed by Novo Nordisk A/S for the treatment of diabetes. It is designed as a long-acting insulin that can be given once weekly, in contrast to conventional daily basal insulins. It has been studied in type 1 and type 2 diabetes.
Insulin icodec is being developed to lower blood sugar in adults with type 1 diabetes and type 2 diabetes. Clinical studies have compared it with daily insulin glargine, including use in combination with insulin aspart and in people with type 2 diabetes who have not previously used insulin.
Insulin icodec targets the insulin receptor, INSR, where it acts as an agonist. By binding and activating this receptor, it promotes glucose uptake and lowers blood glucose, the same receptor pathway engaged by endogenous insulin and other insulin therapies.
Insulin icodec is developed by Novo Nordisk A/S, which trades under the ticker NVO. Novo Nordisk is the sponsor of the clinical trial program evaluating the once-weekly insulin across type 1 and type 2 diabetes populations.
Insulin icodec is an investigational drug still in clinical development, with Phase 1 and Phase 3 studies conducted. It is not described as approved. The program includes 17 completed trials and one active trial that is no longer recruiting participants.
Insulin icodec has been studied in trials including NCT07076199, an active Phase 3 study in type 1 diabetes, NCT06340854, a completed Phase 3 study in type 2 diabetes, NCT06288412, a completed Phase 1 study during exercise and fasting, and NCT05823948, a completed Phase 3 study in type 2 diabetes.