Once-Weekly Insulin: Eli Lilly and Novo Nordisk Trials Update

The Dream of Once-Weekly Insulin

For decades, people with diabetes have structured their lives around daily — sometimes multiple daily — insulin injections. The idea of replacing that routine with a single weekly injection has seemed almost too good to be true. In 2025, that goal is closer to reality than ever before, thanks to major clinical programs from two of the world's largest insulin manufacturers: Eli Lilly and Novo Nordisk.

Novo Nordisk's Insulin Icodec: The First to the Finish Line

Novo Nordisk's once-weekly basal insulin, insulin icodec, has been the subject of the extensive ONWARDS clinical trial program — a series of six Phase 3 trials comparing icodec to existing daily basal insulins (primarily insulin degludec and insulin glargine U100).

The ONWARDS trials enrolled thousands of patients across both Type 1 and Type 2 diabetes. Key findings published in The New England Journal of Medicine and The Lancet showed that icodec achieved non-inferior or superior HbA1c reductions compared to daily basal insulins in most Type 2 diabetes trials, with a comparable or slightly higher rate of hypoglycemia in some arms.

In the ONWARDS 6 trial — the Type 1 diabetes arm — icodec showed non-inferior HbA1c control versus daily degludec when used with mealtime insulin, though hypoglycemia rates were modestly higher, a finding that has led to ongoing caution about its use in Type 1.

Critically, the FDA approved insulin icodec (brand name: Awiqli) in November 2023 for adults with Type 2 diabetes. It became available in the United States in 2024, making it the world's first approved once-weekly insulin. It is also approved in Canada, the EU, and several other markets.

Eli Lilly's Efsitora Alfa: Close Behind

Eli Lilly is running its own once-weekly basal insulin program with efsitora alfa (also called LY3209590), being studied under the QWINT clinical trial program (which stands for QWeekly INsulin Therapy).

The QWINT program includes multiple Phase 3 trials in both Type 1 and Type 2 diabetes. Early results published in 2024 from the QWINT-2 and QWINT-5 trials showed that efsitora achieved statistically significant HbA1c reductions versus daily basal insulin comparators in people with Type 2 diabetes, with a hypoglycemia profile that was broadly comparable.

Efsitora uses a different molecular design than icodec — it is a fusion protein that binds to albumin in the bloodstream, creating a very long-acting depot effect. Both drugs work on the same principle of slow, sustained insulin release, but their pharmacokinetic profiles differ in ways that may affect how quickly dose adjustments take effect — an important clinical consideration.

Eli Lilly submitted efsitora to the FDA for review, and as of mid-2025, a regulatory decision is anticipated. Patients and clinicians can monitor active trial sites at ClinicalTrials.gov by searching "efsitora" or "LY3209590."

How Do Once-Weekly Insulins Work?

Traditional basal insulins like glargine or degludec last roughly 24–42 hours. Once-weekly insulins are engineered to last approximately 160–170 hours (about 7 days). They achieve this through chemical modifications that cause them to bind tightly to albumin, a protein naturally found in your blood, which acts as a slow-release reservoir. The insulin is gradually released from this reservoir over the week, providing steady background insulin coverage.

One important trade-off: because these insulins have such a long half-life, dose adjustments take several weeks to fully stabilize. This means titrating the dose up or down requires patience and careful glucose monitoring — particularly important when starting therapy or during illness.

Current Status (2025)

• Insulin icodec (Awiqli): FDA-approved for Type 2 diabetes in adults. Available by prescription in the US. Not yet approved for Type 1 diabetes due to hypoglycemia concerns — studies are ongoing.
• Efsitora alfa: Under FDA review as of 2025. Phase 3 trial data is positive. Approval decision expected in 2025.
• Type 1 diabetes: Neither drug is currently approved for Type 1. Both companies are conducting dedicated Type 1 trials, but timelines for approval in this population remain unclear.
• Cost and access: Like all newer insulins, coverage and out-of-pocket costs will vary significantly by insurance plan. This is an evolving area to watch.

What This Means for Patients

If you have Type 2 diabetes and use a once-daily basal insulin, once-weekly insulin may already be an option worth discussing with your doctor. The reduced injection burden could meaningfully improve adherence — research consistently shows that fewer injections leads to better real-world compliance.

If you have Type 1 diabetes, once-weekly basal insulin is not yet an approved option, and the increased hypoglycemia risk seen in some trials means it requires careful evaluation. Do not switch insulins without your care team's guidance.

For those managing supplies, devices, and current insulin delivery systems, resources like mdsdiabetes.com offer up-to-date information on diabetes management tools while this technology matures.

One practical note: once-weekly insulins do not eliminate the need for mealtime (bolus) insulin in those who require it. They replace only the basal (background) insulin component.

Realistic Timeline

• 2024–2025: Icodec available in US for Type 2; efsitora FDA decision expected
• 2026–2027: Potential Type 1 approvals if ongoing trials succeed
• Beyond 2027: Broader insurance coverage, real-world outcomes data, and potential biosimilar competition

Once-weekly insulin represents a genuine step forward in diabetes care — not a cure, but a meaningful reduction in daily burden. Watch this space closely.