Insulin icodec

Summary

Insulin icodec is a long‑acting basal insulin analogue approved for prescription use in adults with type 2 diabetes. Engineered for a once‑weekly subcutaneous injection, it provides steady insulin exposure to lower blood glucose, offering a simpler alternative to daily basal insulins such as glargine or degludec.

Mechanism of Action

Icodec binds to the insulin receptor on muscle, adipose and hepatic cells, activating the receptor’s tyrosine kinase cascade. This promotes glucose uptake, suppresses hepatic glucose production and enhances glycogen synthesis. Molecular modifications extend its half‑life, creating a flat, week‑long pharmacokinetic profile that sustains receptor activation with a single weekly dose.

What the Research Shows

Phase 3 ONWARDS 1 (78‑week, insulin‑naïve) showed greater HbA1c reduction (‑1.55% vs ‑1.35%) and more time in target range compared with daily glargine U100, with similar adverse‑event rates. ONWARDS 3 (26 weeks, insulin‑naïve) demonstrated non‑inferior HbA1c lowering versus daily degludec and a modestly higher combined level 2/3 hypoglycaemia rate. ONWARDS 4 (26 weeks, basal‑bolus regimen) found non‑inferior HbA1c change versus glargine U100, comparable hypoglycaemia, and reduced basal injection frequency. ONWARDS 5 (52 weeks, insulin‑naïve) used a dosing‑guide app and reported superior HbA1c decline (‑0.38%) and improved patient‑reported satisfaction versus daily analogues, with low hypoglycaemia. Across trials, safety profiles were similar to existing basal insulins, and no new safety signals emerged.

Reported Benefits

Clinical trials indicate that once‑weekly icodec achieves glycaemic control that is comparable to or better than daily basal insulins, while reducing injection frequency and, in basal‑bolus patients, lowering the required bolus insulin dose. Patient‑reported outcomes suggest higher treatment satisfaction and perceived convenience. Overall hypoglycaemia rates are low and similar to those of established daily analogues.

Limitations of the Evidence

Evidence is limited to 26‑ to 78‑week studies in type 2 diabetes; long‑term cardiovascular outcomes and use in type 1 diabetes remain unstudied. Some trials reported a modest increase in level 2/3 hypoglycaemia (e.g., ONWARDS 3). Open‑label designs and the use of a dosing‑app in ONWARDS 5 make it difficult to isolate drug effects from behavioural factors. Real‑world adherence and comparative cost data are lacking.

Safety Considerations

Adverse‑event frequencies were comparable to glargine U100 and degludec, with serious adverse events occurring in 8‑9% of participants. Combined clinically significant or severe hypoglycaemia was low overall but slightly higher in the icodec group in one trial. No new safety signals were identified, but clinicians should monitor for hypoglycaemia, especially during dose titration, and consider individual patient risk factors.

How It Is Administered

Icodec is delivered by subcutaneous injection, typically using a prefilled pen designed for weekly dosing. Initial dose titration follows a treat‑to‑target algorithm, often supported by a digital dosing‑guide app. No oral or intravenous formulations are available.

Routes of Administration

Goals & Uses

• Reduced injection frequencyPatient ConvenienceHigh
• Reduction of fasting hyperglycemiaMetabolic / EndocrineHigh
• Glycemic control in type 2 diabetesMetabolicHigh
• Improved treatment adherence through reduced injection frequencyPatient Convenience / AdherenceModerate
• Glycemic control in type 1 diabetesMetabolic / EndocrineHigh
• Glycaemic controlDiabetesHigh

Contraindications

• Hypersensitivity to insulin icodec or any excipientAllergyHigh
• Hypoglycemia (during active episode)MetabolicHigh
• Hypersensitivity to insulin icodec or excipientsAllergy / ImmunologicHigh
• Severe hypoglycaemia unawarenessMetabolicModerate

Adverse Effects

• HypokalemiaElectrolyteUncommon
• HypoglycemiaMetabolicCommonAbnormally low blood glucose
• Allergic reactionsImmunologicalRare
• Injection site reactionsLocalCommon
• Injection‑site reactionsLocalUncommon
• HypoglycaemiaMetabolicCommon
• Weight gainMetabolicCommonIncrease in body weight
• LipodystrophyDermatologicUncommon

Drug Interactions

• Oral antidiabetics (e.g., sulfonylureas, meglitinides)Moderate
• Beta‑blockersModerate
• Beta-blockersModerate
• AlcoholModerate
• GLP-1 receptor agonistsLow
• CorticosteroidsModerate
• SulfonylureasHighMay increase risk of low blood sugar

Population Constraints

• PregnancyReproductive SafetyRelative
• Hepatic impairmentOrgan FunctionRelative
• Renal impairmentOrgan ImpairmentRelative
• Pediatric patients (<18 years)AgeRelative
• Pediatric (<18 y)AgeRelative
• Type 1 diabetesDisease SpecificRelative

Regulatory Status

• European UnionApprovedApproved: type 1 diabetes mellitus, type 2 diabetes mellitusMarketing authorisation granted in 2024.
• United StatesApprovedApproved: type 1 diabetes mellitus, type 2 diabetes mellitusApproved for once‑weekly subcutaneous injection in adults.
• United KingdomApprovedApproved: Type 1 diabetes mellitus in adults, Type 2 diabetes mellitus in adultsMHRA approval granted following EMA decision; indicated for adults with type 1 and type 2 diabetes.

Approved by FDA (2024) and EMA (2024) for adult patients with type 1 or type 2 diabetes; dosing requires titration based on fasting glucose. Not indicated for pediatric use or pregnancy without specialist supervision.

Evidence & Sources

• Switching to once-weekly insulin icodec versus once-daily insulin glargine U100 in individuals with basal-bolus insulin-treated type 2 diabetes (ONWARDS 4): a phase 3a, randomised, open-label, multicentre, treat-to-target, non-inferiority trial
  Journal ArticleModerateMathieu C, et al.2023-01-01T00:00:00.000000Z
• Once-Weekly Insulin Icodec With Dosing Guide App Versus Once-Daily Basal Insulin Analogues in Insulin-Naive Type 2 Diabetes (ONWARDS 5) : A Randomized Trial
  Journal ArticleModerateBajaj HS, et al.2023-01-01T00:00:00.000000Z
• Once-Weekly Insulin Icodec vs Once-Daily Insulin Degludec in Adults With Insulin-Naive Type 2 Diabetes: The ONWARDS 3 Randomized Clinical Trial
  Journal ArticleModerateLingvay I, et al.2023-01-01T00:00:00.000000Z
• Weekly Icodec versus Daily Glargine U100 in Type 2 Diabetes without Previous Insulin
  Journal ArticleModerateRosenstock J, et al.2023-01-01T00:00:00.000000Z
• The Basis for Weekly Insulin Therapy: Evolving Evidence With Insulin Icodec and Insulin Efsitora Alfa
  Journal ArticleModerateRosenstock J, et al.2024-01-01T00:00:00.000000Z
• Clinical Use of Once-Weekly Insulin Icodec: Translating Clinical Trial Data into Practical Guidance for Diabetes Management
  Journal ArticleModeratePhilis-Tsimikas A, et al.2025-01-01T00:00:00.000000Z

Frequently Asked Questions