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Insulin efsitora alfa (basal Fc)

Eli Lilly and Company

What it is

A once-weekly basal insulin from Eli Lilly that fuses a single-chain insulin to an IgG Fc domain for a ~17-19 day half-life and a near-flat weekly profile. Phase 3 QWINT-5 matched daily degludec on HbA1c in type 1 diabetes, but severe hypoglycemia was higher (10% vs 3%), mostly during titration. Marketed as Onswik, it is now approved in the US (FDA, September 2026), EU (European Commission, August/September 2026), and UK (MHRA, October 2026) — for adults with type 2 diabetes only. The US FDA label explicitly states Onswik is not recommended in type 1 diabetes due to increased severe hypoglycemia, and NICE discontinued its UK type 1 appraisal in July 2026.

Editorial review: .

Most recent recorded citation date: 2026-10-13. Only explicit date metadata is included; an undated citation may be newer. This does not mean every claim was reviewed on that date.

Trial status, labels and access can change between reviews. How we review the evidence · How to read the evidence

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On the horizonStrong evidencebasallong-actingonce-weeklypipelinefc-fusion

Evidence behind this assessment

Key evidence notes. Study results, product eligibility and access answer different questions.

Who was studied?
Study populations and analysis groups vary. Product age limits alone do not describe who was studied.
Benefit or performance
Consistency: Low within-week variability and stable seven-point glucose profiles in PK/clamp studies; very low immunogenicity (~0.6% in T1D). Scored slightly below its peakless flatness because higher T1D hypoglycemia hints at dose-response sensitivity.Read the supporting discussion; this assessment has no individually linked citation.
Important harms and treatment burden
Read the safety discussion and original sources. A missing summary does not establish safety.
Approval and country access
Country-specific approval and access are not summarized in this record.Approval, trial recruitment, local supply and funding are separate. Check the cited label or access source.
Follow-up and remaining uncertainty
Read the full discussion and original sources for follow-up duration and study limitations.

Research status alone does not establish approval, clinical benefit or local availability.

Editorial score: calculation and evidence

A weighted editorial judgment on a 0–100 scale, not a probability of success or a measured treatment effect. Higher criterion scores mean more favorable assessments.

Default calculation: 35 × 20 + 75 × 25 + 55 × 15 + 45 × 20 + 15 × 10 = 4450; divide by total weight 90. Unrounded weighted result: 49.44444444444444. (Access & cost is excluded from the weighted score until commercial launch.)

Onset speed35

Role convention = basal: onset is deliberately slow. Its long half-life means glucose-lowering builds over days, so a one-time loading dose is needed to avoid early hyperglycemia. Scored neutral-low against basal peers where slow build is acceptable.

Time to peak75

Role convention = basal (flat is GOOD): a near-peakless weekly profile with a steady-state peak-to-trough ratio of just 1.16 (PK) and 1.07 (glucose-lowering), the headline strength of the Fc design.

Short tail55

Role convention = basal (long smooth coverage is GOOD): a ~17-19 day half-life gives uninterrupted week-long coverage with no daily trough. The flip side — exposure cannot be withdrawn quickly — is captured under exercise-flex, not here.

Consistency45

Low within-week variability and stable seven-point glucose profiles in PK/clamp studies; very low immunogenicity (~0.6% in T1D). Scored slightly below its peakless flatness because higher T1D hypoglycemia hints at dose-response sensitivity.

Exercise flexibility15

A fixed weekly depot cannot be dialed down for a planned active day or sick day — the main practical drawback of weekly basals, and a likely contributor to the excess hypoglycemia seen in type 1 diabetes.

Access & cost0

Approved as Onswik in the US (FDA, 23 September 2026), EU (EC Decision C(2026) 5964, published 30 September 2026), and UK (MHRA, 13 October 2026) — for adults with TYPE 2 diabetes only. The US FDA label includes a Limitation of Use and Warning (Section 5.2) stating Onswik is not recommended in type 1 diabetes due to increased risk of severe hypoglycemia (10% vs 3% on degludec), and NICE discontinued its UK type 1 appraisal on 30 July 2026. On-label access for a person with type 1 diabetes remains zero.[2]

Insulins are scored relative to their role peers (see tags: rapid, ultra-rapid, basal, inhaled). A basal insulin's onset score compares it to other basals, not to mealtime insulins.

The full picture

Insulin efsitora alfa (formerly "basal insulin Fc" / BIF / LY3209590; marketed for type 2 diabetes as Onswik) is a once-weekly basal insulin from Eli Lilly. It is built by fusing a single-chain insulin variant — engineered with reduced insulin-receptor affinity — to a human IgG2 Fc domain.11 The Fc portion lets the molecule ride the body's neonatal Fc receptor (FcRn) recycling pathway, which rescues it from degradation and stretches its action out to a week.12 Like all basals, its job is steady background coverage; it does not replace mealtime (bolus) insulin, which people with type 1 diabetes still inject at meals.13

PK/PD — the numbers. Efsitora's defining feature is an extraordinarily long, flat profile. Its half-life is roughly 17 days after a single dose and about 19 days at steady state.1415 Glucose-lowering effect peaks gently around days 4-5 after a dose, and the profile is remarkably even: at steady state the drug-level peak-to-trough ratio is just 1.16, and the glucose-lowering peak-to-trough ratio only 1.07 — essentially a flat line across the week.15 Because of that long half-life, reaching steady state would otherwise take 8-10 weeks, so Lilly uses a one-time loading dose to bring levels up quickly; steady state is then reached between the 4th and 6th weekly dose.15 Within-week exposure varies little, and immunogenicity is very low (treatment-emergent anti-drug antibodies in ~0.6% of type 1 participants), with no measurable effect on clearance, efficacy or safety.16

Absorption variability & exercise. The flat depot means little day-to-day swing in background insulin — good for predictability.14 The trade-off is rigidity: a fixed weekly dose cannot be reduced for a planned active day, illness, or hormonal change. In the type 1 trial, excess lows were concentrated in the first 12 weeks of titration — pointing to dosing, not the molecule, as the challenge.1718

Delivery. Efsitora is given subcutaneously once a week. In the US FDA approval for type 2 diabetes, Onswik is formulated at 500 units/mL (U-500) and 1,000 units/mL (U-1,000) in 3 mL single-patient-use prefilled KwikPens; Lilly has also tested fixed doses in a single-use autoinjector pen.192

Evidence in type 1 diabetes. In the Phase 3 QWINT-5 trial (NCT05463744; 692 adults, 52 weeks), weekly efsitora plus mealtime lispro was non-inferior to daily degludec: HbA1c fell 0.51% vs 0.56% (treatment difference 0.052%).17 But combined level 2/3 hypoglycemia was higher with efsitora (14.03 vs 11.59 events per patient-year; rate ratio 1.21), and severe hypoglycemia hit 10% of efsitora users vs 3% on degludec, concentrated in the first 12 weeks.17 An earlier Phase 2 trial showed similar HbA1c but higher fasting glucose and slightly lower time-in-range (56.1% vs 58.9%).20

The meta-analyses now disagree — and we won't paper over it. A 2025 type-1-specific systematic review found comparable HbA1c but a roughly 2.5-fold higher rate of severe hypoglycemia with weekly basals in type 1 diabetes.21 A June 2026 meta-analysis of five efsitora RCTs (2,562 participants, all comparing against degludec) found no statistically significant difference in hypoglycemia — overall, level 2/3, or nocturnal — in either diabetes type, with an overall HbA1c treatment difference of just 0.08% (95% CI -0.01 to 0.17).10 The catch is that the newer analysis pools type 1 and type 2 together, and its type 1 subgroup is small and wide-intervalled (HbA1c treatment difference 0.10%, 95% CI -0.64 to 0.85) — underpowered for exactly the question a person with type 1 is asking. The hard number that has not moved is from QWINT-5 itself: severe hypoglycemia in 10% of efsitora users versus 3% on degludec, concentrated in the first 12 weeks.17 Until a properly powered type 1 trial with a refined titration protocol reports, we treat weekly basal insulin in type 1 as an unresolved safety question, not a solved one.

Approvals, access & cost. Between August and October 2026, Onswik received marketing authorisation in the EU, US, and UK — exclusively for adults with type 2 diabetes:

  • EU: Following the EMA CHMP's positive opinion in June 2026,67 the European Commission granted marketing authorisation (EU/1/26/2049, Decision C(2026) 5964 of 20 August 2026, published in the Official Journal on 30 September 2026) for the treatment of type 2 diabetes mellitus in adults.4
  • US: On 23 September 2026 (announced 24 September 2026), the US FDA approved ONSWIK (insulin efsitora alfa-gobe, BLA 761408) for adults with type 2 diabetes mellitus.222 Crucially, the US FDA label includes an explicit Limitation of Use (Section 1) and Warning and Precaution (Section 5.2) stating: "ONSWIK is not recommended for use in patients with type 1 diabetes mellitus due to increased risk of severe hypoglycemia. In a 52-week clinical trial of adults with type 1 diabetes mellitus, the incidence of Level 3 (severe) hypoglycemia was higher for patients treated with ONSWIK compared with insulin degludec (10% versus 3%)."2
  • UK: On 13 October 2026, the UK MHRA authorised Onswik for adults with type 2 diabetes via the ACCESS Procedure,5 following NICE's 20 August 2026 final draft guidance for type 2 diabetes.8 On 30 July 2026 NICE discontinued its separate type 1 appraisal after Lilly advised it was not pursuing a UK type 1 marketing authorisation.9

Nothing about these type 2 approvals grants on-label type 1 access, and the FDA's explicit warning against type 1 use mirrors the regulatory headwinds seen with the rival weekly insulin icodec.232

What's coming. While Onswik now moves into commercial launch for adults with type 2 diabetes across the US, EU, and UK,2245 any future path in type 1 diabetes would require refined titration or dosing strategies capable of eliminating the excess severe hypoglycemia seen in QWINT-5.17242

Coming soon

ETA · Approved for TYPE 2 diabetes only as Onswik in the EU (EC Decision C(2026) 5964, 20 August 2026; Official Journal 30 September 2026), US (FDA BLA 761408, 23 September 2026), and UK (MHRA, 13 October 2026). Not approved for type 1 diabetes anywhere: the US FDA label explicitly recommends against use in type 1 diabetes due to increased severe hypoglycemia (10% vs 3% on degludec), and NICE discontinued its UK T1D appraisal on 30 July 2026.

  • →Commercial launch of Onswik for adults with type 2 diabetes in the US, EU, and UK
  • →Type 1 diabetes is excluded from US, EU, and UK licences; the US FDA label carries an explicit Limitation of Use and Warning (Section 5.2) against use in type 1 diabetes, and NICE discontinued its type 1 appraisal on 30 July 2026.

Sources

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    FDA Approval Letter — BLA 761408: ONSWIK (insulin efsitora alfa-gobe) · Regulatory decision · 2026-09-23 — FDA approval letter signed 23 September 2026 (announced 24 September 2026) approving ONSWIK (insulin efsitora alfa-gobe) U-500 and U-1000 KwikPens for adults with type 2 diabetes mellitus.
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    ONSWIK (insulin efsitora alfa-gobe) prescribing information — BLA 761408 (revised 09/2026) · Regulatory decision · 2026-09-23 — US FDA label (posted 5 October 2026): indicated for adults with type 2 diabetes. Section 1 (Limitations of Use) and Section 5.2 state ONSWIK is not recommended for use in patients with type 1 diabetes mellitus due to increased risk of severe hypoglycemia (10% vs 3% with insulin degludec in the 52-week T1D trial).

    U.S. Food and Drug Administration. ONSWIK (insulin efsitora alfa-gobe) prescribing information — BLA 761408 (revised 09/2026; Section 1 Limitations of Use and Section 5.2 Warning: not recommended in type 1 diabetes due to 10% vs 3% severe hypoglycemia).

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    Union Register of medicinal products — Onswik (EU/1/26/2049) · Regulatory decision · 2026-09-30 — European Commission Decision C(2026) 5964 of 20 August 2026 (published in Official Journal OJ C 4919 on 30 September 2026) granting EU marketing authorisation for Onswik in adults with type 2 diabetes mellitus.

    European Commission. Union Register of medicinal products — Onswik (EU/1/26/2049) (Commission Decision C(2026) 5964 of 20 August 2026; published in Official Journal OJ C 4919 on 30 September 2026).

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    MHRA authorises Onswik (insulin efsitora alfa) for adults with type 2 diabetes · Regulatory decision · 2026-10-13 — UK MHRA marketing authorisation granted 13 October 2026 for adults with type 2 diabetes via the ACCESS Procedure.

    Medicines and Healthcare products Regulatory Agency. MHRA authorises Onswik (insulin efsitora alfa) for adults with type 2 diabetes (13 October 2026).

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    Meeting highlights from the Committee for Medicinal Products for Human Use (CHMP) 22-25 June 2026 — Onswik (insulin efsitora alfa) positive opinion for type 2 diabetes · Regulatory decision · 2026-06-26 — CHMP recommended marketing authorisation for Onswik (Eli Lilly Nederland B.V.) in adults with type 2 diabetes.

    European Medicines Agency. Meeting highlights from the Committee for Medicinal Products for Human Use (CHMP) 22-25 June 2026 — positive opinion for Onswik (insulin efsitora alfa) in type 2 diabetes (2026).

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    Onswik (insulin efsitora alfa) — EMA EPAR page · Regulatory decision · 2026-06-26

    European Medicines Agency. Onswik (insulin efsitora alfa) EPAR.

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    Insulin efsitora alfa for treating type 2 diabetes [ID6499] · Regulatory decision · 2026-08-20 — NICE type 2 technology appraisal. Final draft guidance published 20 August 2026. Type 2 only.

    NICE. Insulin efsitora alfa for treating type 2 diabetes [ID6499] — final draft guidance 20 August 2026.

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    Insulin efsitora alfa for treating type 1 diabetes in people on multiple daily insulin injections [ID6498] — discontinued · Regulatory decision · 2026-07-30 — Discontinued 30 July 2026. Suspended 22 July 2025 after Lilly advised it was no longer pursuing an MHRA marketing authorisation for the type 1 indication.

    NICE. Insulin efsitora alfa for treating type 1 diabetes in people on multiple daily insulin injections [ID6498] — discontinued 30 July 2026.

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    Copur S, Mizrak B, Ozbek L, et al. Once-Weekly Subcutaneous Insulin Efsitora for the Management of Diabetes Mellitus: A Systematic Review and Meta-Analysis Study. Medeniyet Medical Journal 2026;41(2):203-211 · Peer-reviewed study · 2026-06-30 — 5 RCTs, 2,562 patients (1,358 efsitora / 1,204 degludec). No statistically significant difference in overall, level 2/3 or nocturnal hypoglycemia vs degludec. Overall HbA1c treatment difference 0.08% (95% CI -0.01 to 0.17). The type 1 subgroup is small with a very wide interval (ETD 0.10%, 95% CI -0.64 to 0.85) — underpowered for type 1 specifically.

    Copur S, Mizrak B, Ozbek L, et al. Once-Weekly Subcutaneous Insulin Efsitora for the Management of Diabetes Mellitus: A Systematic Review and Meta-Analysis Study. Medeniyet Medical Journal (2026);41(2):203-211; DOI 10.4274/MMJ.galenos.2026.35858.

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    Heise T, Chien J, Beals JM, et al. Pharmacokinetic and pharmacodynamic properties of the novel basal insulin Fc (insulin efsitora alfa). Diabetes Obes Metab (2023). https://pubmed.ncbi.nlm.nih.gov/36541037/

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    Rosenstock J, Juneja R, Beals JM, et al. The Basis for Weekly Insulin Therapy: Evolving Evidence With Insulin Icodec and Insulin Efsitora Alfa. Endocr Rev (2024). https://pmc.ncbi.nlm.nih.gov/articles/PMC11091825/

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    Denimal D. Emerging perspectives on once-weekly insulins in type 1 and type 2 diabetes: a mini-review. Front Endocrinol (2025). https://pmc.ncbi.nlm.nih.gov/articles/PMC12420296/

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    Heise T, Chien J, Beals JM, et al. PK/PD properties of basal insulin Fc (insulin efsitora alfa). Diabetes Obes Metab (2023); DOI 10.1111/dom.14956. https://doi.org/10.1111/dom.14956

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    Leohr J, Klein O, Heise T, et al. Characterisation of steady-state pharmacokinetics and glucodynamics of once-weekly insulin efsitora alfa in type 2 diabetes. Diabetes Obes Metab (2026). https://pubmed.ncbi.nlm.nih.gov/41725424/

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    Wang Y, Wang S, Wang W, et al. Low immunogenicity of insulin efsitora alfa in type 1 and type 2 diabetes. Diabetes Obes Metab (2025). https://pmc.ncbi.nlm.nih.gov/articles/PMC12803677/

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    Bergenstal RM, Weinstock RS, Mathieu C, et al. Once-weekly insulin efsitora alfa versus once-daily insulin degludec in adults with type 1 diabetes (QWINT-5): a phase 3 randomised non-inferiority trial. Lancet (2024);404:1132-1142. https://pubmed.ncbi.nlm.nih.gov/39270686/

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    Kazda CM, Bue-Valleskey JM, Chien J, et al. Novel Once-Weekly Basal Insulin Fc Achieved Similar Glycemic Control With a Safety Profile Comparable to Insulin Degludec in Patients With Type 1 Diabetes. Diabetes Care (2023);46:1052-1059. https://pmc.ncbi.nlm.nih.gov/articles/PMC10154655/

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    DeLuca A, Schultz A, Ofori H, et al. The Safety, Efficacy, and Clinical Use of Novel Once-Weekly Insulins in the Management of Diabetes. Expert Opin Drug Saf (2025); DOI 10.1080/14740338.2025.2593372. https://doi.org/10.1080/14740338.2025.2593372

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    Ramachandran A, Batra J, Desouza C. Evaluating once-weekly insulin efsitora alfa for adults with type 2 diabetes. Expert Opin Pharmacother (2026); DOI 10.1080/14656566.2026.2667324. https://doi.org/10.1080/14656566.2026.2667324