Novo's Rejected Insulin Makes a Comeback

The FDA approved Awiqli, Novo Nordisk's once-weekly basal insulin, on March 26, 2026. The approval itself is a first — no other basal insulin has required fewer than one injection per day — but the more interesting story is in the fine print. Novo Nordisk got a rejection on this exact drug fourteen months ago. This approval is the comeback.

Awiqli (insulin icodec-abae) is cleared for adults with type 2 diabetes, not type 1, and the label carries no asterisks about manufacturing. Novo Nordisk resubmitted its biologics license application in September 2025 after the FDA issued a Complete Response Letter in July 2024 citing manufacturing process issues and — more consequentially — safety concerns for type 1 diabetes patients. The Endocrinologic and Metabolic Drugs advisory committee had already voted 7-4 against recommending approval in May 2024, according to PharmExec coverage. Novo quietly dropped type 1 from the resubmission and won on type 2. The company expects to launch Awiqli in the U.S. in the second half of 2026, according to Reuters.

The clinical case for type 2 patients is real. The ONWARDS phase 3a program enrolled approximately 2,680 adults with uncontrolled type 2 diabetes across four randomized, active-controlled trials and showed icodec reduced HbA1c by a mean of 0.2 percentage points more than daily insulin degludec, a difference that was statistically significant. A meta-analysis of the ONWARDS 1–5 trials found an estimated treatment difference of −0.17 percentage points in HbA1c favoring icodec (95% CI −0.28 to −0.06, p=0.003), published in Diabetes, Obesity and Metabolism.

The once-weekly dosing works because insulin icodec binds albumin reversibly via a C20 icosane fatty diacid chain, extending its half-life to approximately 196 hours — meaning it reaches steady state after three to four weekly injections, according to a study published in PMC. For type 2 patients — particularly the elderly, the cognitively impaired, and anyone for whom daily injections are a genuine adherence barrier — fewer pokes matter. Julio Rosenstock, a principal investigator on the ONWARDS program and researcher at UT Southwestern Medical Center, said in a Novo Nordisk press release that research supports weekly injectable diabetes medications can be associated with improved patient adherence. That is a careful, evidence-backed way of saying people are more likely to take a medicine they don't have to think about every single day.

Nearly one in five U.S. adults already rations insulin because of cost, according to a FiercePharma analysis of insulin spending data. Novo Nordisk has been cutting list prices — Fiasp by 75 percent and Tresiba by 72 percent effective January 2026 — but a weekly injectable doesn't solve a cost problem. Novo Nordisk CEO Mike Doustdar put it diplomatically in the company's approval statement: at a time when parts of the industry are stepping back from insulin, we are reaffirming our commitment to the millions of patients who rely on it every day. That is both a genuine patient-centric message and a competitive positioning play against Eli Lilly, which is developing its own once-weekly basal insulin called efsitora alfa.

Eli Lilly's efsitora posted stronger HbA1c numbers in its QWINT-3 trial — a reduction of 0.86 percent versus 0.75 percent for degludec at 26 weeks — and the company submitted it for regulatory approval in the U.S., EU, and Japan in 2025, according to its investor relations statement. Novo Nordisk got to market first in the U.S., but this race is far from over.

What the type 1 diabetes community is left with is a drug that actually met its A1c non-inferiority target in the ONWARDS 6 trial — the estimated treatment difference was +0.05 percentage points, well within the pre-specified 0.3 margin — but was rejected anyway because of hypoglycemia. The weekly insulin carried a statistically significantly higher rate of clinically significant or severe hypoglycemia in type 1 patients: 19.9 versus 10.4 events per patient-year of exposure (rate ratio 1.9, p<0.0001), according to the Lancet paper. The advisory committee's 7-4 rejection in May 2024 was explicitly about whether the hypoglycemia risk outweighed the A1c benefit, not about whether the drug worked. Novo Nordisk is doing it anyway. That is what a Complete Response Letter followed by a strategic pivot looks like when it works.

Novo Nordisk's VP Anna Windle said in the company's approval press release that Awiqli may address challenges associated with the frequency of daily basal injections by reducing them from seven to one per week. For type 2 patients who can access it, that reduction in friction may matter more than the marginal HbA1c difference. The drug is already approved in the EU and 13 additional countries as of March 2026, according to the company's press release on PRNewswire. U.S. launch is second half of 2026.