In Development Pipeline & In-Development

Insulin efsitora alfa

also known as: efsitora, efsitora alfa, LY3209590, basal insulin Fc

Lilly's once-weekly basal insulin candidate — Phase 3 QWINT program completed 2024 in T1DM and T2DM; NDA submission 2025. Competes head-to-head with Novo's insulin icodec, using Fc fusion rather than albumin binding to achieve the weekly profile.

A once-weekly basal insulin analog (Eli Lilly) constructed as a single-chain insulin variant fused to an IgG2 Fc region via a peptide linker — FcRn-mediated recycling and slow receptor-mediated clearance produce a plasma half-life of approximately 17 days. The Phase 3 QWINT program (five trials in T1DM and T2DM) read out in 2024 with non-inferior glycemic control versus daily basal analogs; NDA submission 2025 and FDA review ongoing.

Mechanism of action

Insulin receptor agonism via a single-chain insulin analog engineered with reduced insulin receptor affinity and IgG2 Fc fusion. The Fc fusion provides FcRn-mediated recycling (the same half-life-extending mechanism used by monoclonal antibodies), while the attenuated receptor affinity slows receptor-mediated clearance. Together these produce ultra-long half-life and a flat PK profile.

Primary uses

  • Type 2 diabetes mellitus (Phase 3 complete)
  • Type 1 diabetes mellitus (Phase 3 complete)

Typical dosing

once weekly (subcutaneous)

QWINT program used flexible initiation/titration protocols. Typical T2DM weekly dose approximately 7× equivalent daily basal dose.

Regulatory status

Not yet approved. Phase 3 QWINT program (QWINT-1 through QWINT-5) completed 2024. Lilly announced NDA submission 2025. FDA review ongoing.

References

  1. [pubmed] Bue-Valleskey JM, et al. "Insulin efsitora alfa weekly versus insulin degludec daily in insulin-naive type 2 diabetes (QWINT-2)." N Engl J Med, 2024;391:1940-1950.
  2. [pubmed] Kazda CM, et al. "Once-weekly basal insulin Fc in T1D and T2D." JAMA, 2022;328:2030-2041.
  3. [manufacturer] Eli Lilly. Press release: QWINT Phase 3 topline results, 2024.

Related peptides

Insulin icodec

Novo Nordisk's once-weekly basal insulin (Awiqli, EMA 2024) — the first weekly insulin to reach market; FDA refused to approve in July 2024 (CRL citing type 1 diabetes hypoglycemia data), leaving it approved in the EU, UK, Canada, Switzerland, and Japan while pending US resubmission.

Insulin degludec

Novo Nordisk's ultra-long-acting insulin (Tresiba, 2015) — forms soluble multi-hexamers in SC tissue that slowly dissociate for a >42-hour half-life and a flat, forgiving dosing window; the basal insulin with the lowest hypoglycemia risk profile.

Insulin glargine

The dominant once-daily basal insulin for two decades (Lantus, Sanofi, 2000) — the pI-shift design causes microprecipitation in subcutaneous tissue for a nearly peakless 24-hour absorption profile; Toujeo (U-300) is the same molecule at 3× concentration.
Disclaimer

This entry is for educational purposes only and does not constitute medical advice. Dosing information reflects published regulatory or research data and is not a recommendation. Many compounds described here are not approved for human use in the United States. Consult a licensed medical professional before considering any peptide therapy.