Insulin efsitora alfa
A weekly basal insulin, approved in September 2026 for type 2 diabetes and kept away from type 1
Insulin efsitora alfa is Eli Lilly's once-weekly basal insulin: a single-chain insulin variant fused to the Fc fragment of a human antibody, which gives it a half-life of about 17 to 19 days. FDA approved it as Onswik in September 2026 for adults with type 2 diabetes, after four QWINT trials in more than 3,400 people found it lowered HbA1c as well as daily glargine or degludec. It is not for type 1 diabetes, where its trial showed more severe hypoglycaemia.
What is it?
Basal insulin has meant a daily injection for as long as long-acting insulins have existed. Insulin efsitora alfa, developed by Eli Lilly under the code LY3209590 and first called basal insulin Fc, changes that by fusing a single-chain insulin variant to the Fc fragment of a human antibody. The Fc portion slows its clearance so much that its half-life is about 17 days, and at steady state the level barely moves across the week: a peak-to-trough ratio of about 1.1.
The QWINT phase 3 programme tested it in four trials in type 2 diabetes, in people starting insulin (QWINT-1 and QWINT-2), people already on basal insulin (QWINT-3) and people on basal plus mealtime insulin (QWINT-4). In every one it met its primary goal: HbA1c lowering non-inferior to once-daily glargine or degludec. QWINT-1 used a fixed-dose regimen, a few set dose steps like those used for weekly GLP-1 medicines, and needed a median of 2 dose adjustments against 8 for glargine.
A fifth trial, QWINT-5, tested it in type 1 diabetes. HbA1c lowering was again non-inferior, but level 2 and severe hypoglycaemia were more frequent than with degludec. The approval reflects that: Onswik is indicated for adults with type 2 diabetes, and people with type 1 diabetes should not use it because of the higher risk of severe low blood sugar.
FDA approved Onswik in September 2026, the second once-weekly basal insulin after Novo Nordisk's insulin icodec, and Lilly lists earlier approvals from the European Medicines Agency, Japan and Mexico. Its high-concentration pens, delivering hundreds of units in one injection, make careful dose selection part of its safety profile.
Mechanism of Action
Efsitora does what basal insulin does; what is new is how slowly it does it.
Insulin receptor agonism
Efsitora activates the insulin receptor, suppressing the liver's glucose output and supporting glucose uptake between meals, the job of any basal insulin. Its single-chain insulin variant was designed for weekly exposure rather than for speed.
Fc fusion and slow clearance
Fusion to a human IgG2 Fc domain slows clearance, giving a half-life of about 17 days after single doses and 19 days at steady state, far longer than daily basal insulins.
A flat weekly profile
At steady state the concentration peak is only about 14% to 16% above the trough, and in a clamp study the glucose-lowering effect was spread evenly across the week (peak-to-trough 1.07), with its maximum between days 4 and 5.
Weeks to steady state
A long half-life means changes take time to settle: with a one-time loading dose, steady state was reached between the fourth and sixth weekly doses, which is why dose steps come at four-week intervals.
Published Research
These are the trials behind efsitora, read from their PubMed abstracts: the QWINT phase 3 programme, the phase 2 trials that preceded it and the pharmacology studies that measured its weekly profile.
QWINT-1: a fixed-dose weekly regimen against daily glargine
In adults with type 2 diabetes starting insulin, once-weekly efsitora given in a fixed-dose regimen was non-inferior to daily glargine in lowering HbA1c over 52 weeks. The mean weekly insulin dose was lower (289.1 against 332.8 units), and the median number of dose adjustments was 2 against 8.
QWINT-2: against degludec in people starting insulin
HbA1c fell from 8.21% to 6.97% with efsitora and from 8.24% to 7.05% with degludec over 52 weeks (treatment difference minus 0.09 points, 95% CI minus 0.22 to 0.04), meeting non-inferiority in participants who were and were not using GLP-1 receptor agonists.
QWINT-3: switching from daily basal insulin
Of 1,229 people with type 2 diabetes already on basal insulin, 986 were randomised (655 to efsitora, 331 to degludec) and 88% completed 78 weeks. The primary comparison, HbA1c change at week 26 against a non-inferiority margin of 0.4 points, was met, according to the trial report and the manufacturer.
QWINT-4: with mealtime insulin, against glargine
In people using basal and mealtime insulin, HbA1c at week 26 was 7.17% with efsitora and 7.18% with glargine, a fall of 1.01 against 1.00 points. Level 2 or severe hypoglycaemia occurred at similar rates (6.6 against 5.9 events per patient-year).
QWINT-5: type 1 diabetes, against degludec
HbA1c fell 0.51 points with efsitora and 0.56 with degludec over 26 weeks (difference 0.052, non-inferior), but level 2 or severe hypoglycaemia was more frequent with efsitora (14.03 against 11.59 events per patient-year). Efsitora was not approved for type 1 diabetes.
Phase 2 in type 1 diabetes
In 265 people with type 1 diabetes on multiple daily injections, weekly basal insulin Fc was non-inferior to degludec on HbA1c at 26 weeks, with a difference of 0.17 points favouring degludec; time in range was similar (56.1% against 58.9%).
Phase 2 in type 2 diabetes already on basal insulin
People with type 2 diabetes on basal insulin were randomised to one of two weekly titration algorithms, with different fasting-glucose targets and a one-time loading dose of 1.5 to 3 times the calculated weekly dose, or to daily degludec, the design that informed the phase 3 dosing.
First human pharmacokinetics
In healthy participants and people with type 2 diabetes, basal insulin Fc had a half-life of about 17 days and lowered fasting glucose for five days or longer after a single dose; after six weekly doses the peak-to-trough ratio was 1.14, glucose profiles were similar to glargine, and no severe hypoglycaemia occurred.
Steady-state pharmacokinetics in a clamp study
In 56 insulin-naive adults with type 2 diabetes, steady state was reached between the fourth and sixth weekly doses with a loading dose; the half-life was 19 days, the pharmacokinetic peak-to-trough ratio 1.16, and the glucose-lowering effect's ratio 1.07, with its maximum between days 4 and 5.
Hypoglycaemia under provocation
In an exploratory phase 1 study, most hypoglycaemia under prolonged fasting, fasting with exercise, or a deliberate double dose was level 1, and its incidence did not differ significantly from glargine (for example 44.7% against 42.6% with prolonged fasting).
QWINT-1 by final dose
Among 303 efsitora-treated participants in QWINT-1, this analysis describes baseline characteristics and outcomes by the fixed dose each reached at week 52, the regimen's four-step design in practice.
Preclinical characterisation of basal insulin Fc
The preclinical work describes the molecule, a novel single-chain insulin variant fused to an Fc domain, and characterises its receptor activity and extended exposure in animals before human testing.
Design of the QWINT programme
The five QWINT trials covered insulin-naive adults with type 2 diabetes (QWINT-1 and -2), adults already on basal insulin (QWINT-3 and -4) and adults with type 1 diabetes (QWINT-5).
The basis for weekly insulin
A review of the evidence for once-weekly basal insulins, tracing the move from daily suspensions to insulin icodec and insulin efsitora alfa and what their long half-lives mean for titration and hypoglycaemia.
Dosing Data
Onswik's US label was not yet on DailyMed when this page was written, so the doses here are the QWINT-1 regimen and the pen facts from Lilly's approval announcement.
Educational information, not medical advice. Each dose above is tagged with its source: an approved label, a published human study, animal data, or amounts reported by users. None is a recommendation for you. An unapproved compound has no established safe or effective human dose, and products sold for “research use only” are not made or tested for people. Talk to a doctor before acting on anything on this site, including before you start, stop or change any medicine or dose. Full medical disclaimer.
Side Effects & Contraindications
Reported Side Effects
The manufacturer's summary lists the common side effects; the trials give hypoglycaemia rates.
Contraindications & Cautions
The indication itself carries the most important restriction.
Legal Status
Efsitora became an approved medicine in 2026, in type 2 diabetes only.
Frequently Asked Questions
?Is insulin efsitora approved?
Yes. FDA approved it as Onswik in September 2026 for adults with type 2 diabetes, and Lilly lists earlier approvals in the EU, Japan and Mexico. It is not approved for type 1 diabetes.
?Why is efsitora not for type 1 diabetes?
In QWINT-5, in type 1 diabetes, it lowered HbA1c as well as degludec but caused more level 2 or severe hypoglycaemia (14.03 against 11.59 events per patient-year). Lilly's safety summary says people with type 1 diabetes should not use it.
?How does a weekly insulin last a week?
Efsitora is fused to the Fc fragment of a human antibody, which slows its clearance to a half-life of about 17 to 19 days. At steady state its level varies only about 14% to 16% across the week.
?How is efsitora dosed?
Once a week on the same day. In QWINT-1 people starting insulin began at 100 units a week and moved through fixed steps of 150, 250 and 400 units every four weeks as needed, which took a median of 2 dose changes against 8 with daily glargine.
?How does efsitora compare with insulin icodec?
Both are once-weekly basal insulins approved for type 2 diabetes in the US, icodec first (March 2026). Icodec binds albumin to last a week; efsitora uses an antibody Fc fragment. No head-to-head trial is in our sources.
?What are the main risks?
Low blood sugar above all, plus allergic and injection-site reactions, low potassium, weight gain, and heart failure when combined with thiazolidinediones. Its high-concentration pens make correct dose selection especially important.
References
- [pubmed] Rosenstock J, et al. "Weekly Fixed-Dose Insulin Efsitora in Type 2 Diabetes without Previous Insulin Therapy." N Engl J Med, 2025;393(4):325-335. PMID: 40548694.
- [pubmed] Wysham C, et al. "Insulin Efsitora versus Degludec in Type 2 Diabetes without Previous Insulin Treatment." N Engl J Med, 2024;391(23):2201-2211. PMID: 39254740.
- [pubmed] Philis-Tsimikas A, et al. "Once-weekly insulin efsitora alfa versus once-daily insulin degludec in adults with type 2 diabetes currently treated with basal insulin (QWINT-3): a phase 3, randomised, non-inferiority trial." Lancet, 2025;405(10497):2279-2289. PMID: 40562047.
- [pubmed] Blevins T, et al. "Once-weekly insulin efsitora alfa versus once-daily insulin glargine U100 in adults with type 2 diabetes treated with basal and prandial insulin (QWINT-4): a phase 3, randomised, non-inferiority trial." Lancet, 2025;405(10497):2290-2301. PMID: 40562048.
- [pubmed] Bergenstal RM, 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(10458):1132-1142. PMID: 39270686.
- [pubmed] Kazda CM, 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(5):1052-1059. PMID: 36920867.
- [pubmed] Frias J, et al. "Safety and efficacy of once-weekly basal insulin Fc in people with type 2 diabetes previously treated with basal insulin: a multicentre, open-label, randomised, phase 2 study." Lancet Diabetes Endocrinol, 2023;11(3):158-168. PMID: 36758572.
- [pubmed] Heise T, et al. "Pharmacokinetic and pharmacodynamic properties of the novel basal insulin Fc (insulin efsitora alfa), an insulin fusion protein in development for once-weekly dosing for the treatment of patients with diabetes." Diabetes Obes Metab, 2023;25(4):1080-1090. PMID: 36541037.
- [pubmed] Leohr J, et al. "Characterisation of steady-state pharmacokinetics and glucodynamics of once-weekly insulin efsitora alfa in individuals with type 2 diabetes." Diabetes Obes Metab, 2026;28(5):4010-4018. PMID: 41725424.
- [pubmed] Heise T, et al. "Frequency and Severity of Hypoglycemia Under Conditions of Increased Hypoglycemic Risk with Insulin Efsitora Alfa Versus Insulin Glargine Treatment in Participants with Type 2 Diabetes." Diabetes Ther, 2024;15(8):1785-1797. PMID: 38907935.
- [pubmed] Connery L, et al. "Glycaemic Control According to the Final Insulin Dose Using an Innovative Fixed-Dose Titration of Weekly Insulin Efsitora in Insulin-Naïve Type 2 Diabetes." Diabetes Obes Metab, 2026;28(7):6217-6224. PMID: 42070786.
- [pubmed] Moyers JS, et al. "Preclinical Characterization of LY3209590, a Novel Weekly Basal Insulin Fc-Fusion Protein." J Pharmacol Exp Ther, 2022;382(3):346-355. PMID: 35840338.
- [pubmed] Bergenstal RM, et al. "Once-weekly insulin efsitora alfa: Design and rationale for the QWINT phase 3 clinical development programme." Diabetes Obes Metab, 2024;26(8):3020-3030. PMID: 38679838.
- [pubmed] Rosenstock J, et al. "The Basis for Weekly Insulin Therapy: Evolving Evidence With Insulin Icodec and Insulin Efsitora Alfa." Endocr Rev, 2024;45(3):379-413. PMID: 38224978.
- [fda] FDA. Drugs@FDA (openFDA), BLA 761408: ONSWIK (insulin efsitora alfa-gobe), Eli Lilly and Co; original approval September 23, 2026; marketing status Prescription. Read September 30, 2026.
- [manufacturer] Eli Lilly and Company. U.S. Food and Drug Administration (FDA) approves Lilly's Onswik (insulin efsitora alfa-gobe), a once-weekly basal insulin injection treatment for adults living with type 2 diabetes. Press release, September 24, 2026. Read September 30, 2026.
- [fda-pi] Eli Lilly and Company. ONSWIK (insulin efsitora alfa-gobe) injection, US prescribing information, revised 09/2026 (ONS-0001-USPI-20260923), pi.lilly.com; not yet on DailyMed. Read September 30, 2026.
Sources & Citations
Every study on this page was read from its PubMed record. The approval date and application number come from FDA's Drugs@FDA database, and the indication, pens and safety summary from Lilly's announcement of September 24, 2026; the US label was not yet on DailyMed.
Medical Disclaimer: This content is for educational and informational purposes only. It is not medical advice, and nothing here is an instruction to obtain or use any compound. Talk to a licensed clinician about your own situation.