Skip to content
type1.science

Insulin efsitora alfa (basal Fc)

Eli Lilly and Company

An investigational 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, mostly during titration. Not approved as of 2026.

On the horizonStrong evidencebasallong-actingonce-weeklypipelinefc-fusion

The scorecard

Onset speed45

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 peak88

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) — among the flattest of any basal, the headline strength of the Fc design.

Short tail85

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 The flip side — exposure cannot be withdrawn quickly — is captured under exercise-flex, not here.

Consistency80

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 flexibility30

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 non-nocturnal hypoglycemia seen in type 1 diabetes.

Access & cost20

Not yet approved anywhere as of 2026 (Phase 3 complete, regulatory submissions filed). No price, no biosimilars; planned fixed-dose autoinjector could ease access if approved, but availability is currently zero.

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) is an investigational 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.1 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.2 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.3

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.45 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.5 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.5 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.6

Absorption variability & exercise. The flat depot means little day-to-day swing in background insulin — good for predictability.4 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 driven by non-nocturnal episodes, and 64% of severe hypoglycemia events occurred during the titration period — pointing to dosing, not the molecule, as the challenge.78

Delivery. Efsitora is given subcutaneously once a week. Lilly has tested fixed doses in a single-use autoinjector pen, with a multi-dose KwikPen for people needing higher doses.9

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%).7 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.7 An earlier Phase 2 trial showed similar HbA1c but higher fasting glucose and slightly lower time-in-range (56.1% vs 58.9%).10 Meta-analyses confirm comparable HbA1c but a roughly 2.5-fold higher rate of severe hypoglycemia in type 1 diabetes.11

Approvals, access & cost. As of 2026, efsitora is not approved anywhere; the Phase 3 QWINT program is complete and regulatory submissions have been filed.127 There is no price and no biosimilar. Context matters: the FDA's advisory committee voted against the rival weekly insulin icodec in type 1 diabetes over hypoglycemia, so the type 1 pathway for weekly basals faces real scrutiny.13

What's coming. The near-term opportunity is type 2 diabetes, where QWINT-1/3/4 showed clean non-inferiority with low severe-hypoglycemia rates; type 1 use will likely hinge on refined titration protocols to tame the early-weeks hypoglycemia signal.712 If approved, efsitora would cut basal injections from 365 to 52 per year — a meaningful adherence lever, especially for people who struggle with daily dosing.3

References

  1. 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/ ↩

  2. 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://www.ncbi.nlm.nih.gov/pmc/articles/PMC11091825/ ↩

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

  4. 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 ↩ ↩2

  5. 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/ ↩ ↩2 ↩3

  6. 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://www.ncbi.nlm.nih.gov/pmc/articles/PMC12803677/ ↩

  7. 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/ ↩ ↩2 ↩3 ↩4 ↩5

  8. Once-weekly basal insulin therapy in type 1 diabetes: a paradigm shift or a work in progress? Am J Health Syst Pharm (2025); DOI 10.1093/ajhp/zxaf169. https://doi.org/10.1093/ajhp/zxaf169 ↩

  9. Eli Lilly. In a first-of-its-kind fixed dose study, once weekly insulin efsitora alfa leads to A1C reduction similar to daily insulin (QWINT-1). PR Newswire (2024). https://www.prnewswire.com/news-releases/in-a-first-of-its-kind-fixed-dose-study-once-weekly-insulin-efsitora-alfa-leads-to-a1c-reduction-similar-to-daily-insulin-302238497.html ↩

  10. 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://www.ncbi.nlm.nih.gov/pmc/articles/PMC10154655/ ↩

  11. Di Gioia L, Di Molfetta S, Caruso I, et al. Efficacy and safety of once-weekly basal insulin therapy in people with type 1 diabetes: a systematic review and meta-analysis. Diabetes Obes Metab (2025). https://pubmed.ncbi.nlm.nih.gov/41048193/ ↩

  12. 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 ↩ ↩2

  13. 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 ↩

Coming soon

ETA · Phase 3 QWINT program complete and regulatory submissions filed; not approved anywhere as of 2026. Type 1 use likely hinges on refined titration protocols.

  • →Near-term opportunity is type 2 diabetes approval (QWINT-1/3/4 showed clean non-inferiority); type 1 use will hinge on refined titration protocols to tame early-weeks hypoglycemia
  • →If approved, would cut basal injections from 365 to 52 per year