FDA Approves First Once-Weekly Insulin for Type 2 Diabetes, Ending Two Decades of Daily Injections
Novo Nordisk's Awiqli reduces basal insulin injections from 365 to 52 per year, winning FDA approval after a 2024 rejection over manufacturing and safety concerns.
Overview
The U.S. Food and Drug Administration approved Awiqli (insulin icodec-abae) on March 26, 2026, making it the first and only once-weekly basal insulin available for adults with type 2 diabetes, according to Novo Nordisk’s announcement. The approval marks the first change to basal insulin dosing frequency in more than two decades, since the introduction of once-daily long-acting analogs such as insulin glargine around the year 2000.
Administered via the FlexTouch prefilled pen on the same day each week, Awiqli reduces the number of basal insulin injections from 365 to 52 per year. Novo Nordisk expects to launch the drug in the United States in the second half of 2026.
What We Know
The approval is based on the ONWARDS phase 3a clinical trial program, which comprised four randomized, active-controlled, treat-to-target trials enrolling approximately 2,680 adults with uncontrolled type 2 diabetes, as detailed in Novo Nordisk’s announcement. The trials evaluated once-weekly Awiqli against daily basal insulins, including insulin glargine U-100 and insulin degludec, in combination with mealtime insulin or common oral anti-diabetic agents and GLP-1 receptor agonists.
According to the FDA clinical review of insulin icodec, the ONWARDS trials demonstrated the following results in insulin-naive populations:
- ONWARDS 1 (52 weeks): Insulin icodec showed an HbA1c reduction advantage of 0.19 percentage points over insulin glargine, with 4.27 percentage points greater time in the target glycemic range (71.27% versus 67.00%)
- ONWARDS 3 (26 weeks): A 0.21 percentage-point HbA1c advantage over insulin degludec
- ONWARDS 5 (52 weeks): A 0.38 percentage-point HbA1c advantage over daily analogs
In insulin-experienced patients, ONWARDS 2 showed a 0.22 percentage-point advantage over degludec, while ONWARDS 4 showed essentially equivalent results to glargine. Across the program, patients receiving icodec achieved an HbA1c below 7% without hypoglycemia at higher rates than those on daily insulin, according to the clinical review.
The drug’s safety profile was described as overall consistent with the daily basal insulin class. However, the clinical review noted that more level 2 hypoglycemic events occurred with insulin icodec in four of five trials, with ONWARDS 1 showing 1.67 times more events in the icodec group, though concentrated among a small number of patients.
The Road to Approval
Awiqli’s path to market was not straightforward. In July 2024, the FDA issued a Complete Response Letter rejecting the original application, citing concerns about the manufacturing process and the type 1 diabetes indication, as reported by Fierce Pharma. The rejection followed an FDA advisory committee vote in May 2024 that determined, by a 7-4 margin, that the available data were insufficient to conclude benefits outweighed risks. Panelists pointed to heightened hypoglycemia risk compared to once-daily insulin degludec in patients with type 1 diabetes.
Novo Nordisk resubmitted the application in September 2025, this time focusing exclusively on type 2 diabetes to avoid further delays, according to the company’s resubmission announcement. The resubmission was supported by results from five randomized trials enrolling approximately 4,000 adults with type 2 diabetes. A separate trial for patients with type 1 diabetes is planned.
What We Don’t Know
Several significant questions remain unanswered. Novo Nordisk has not disclosed a U.S. list price for Awiqli, and it remains unclear how insurers and pharmacy benefit managers will cover the new formulation relative to existing daily insulins that are available as biosimilars at lower cost.
The long-term safety profile beyond the trial period also warrants monitoring. Because insulin icodec has a prolonged duration of action, dose adjustments take longer to take effect, which could present challenges for patients whose insulin needs fluctuate due to illness, changes in diet, or varying activity levels. The clinical review noted that treatment compliance scores favored weekly dosing, but real-world adherence data outside of controlled trial settings are not yet available.
Awiqli also faces emerging competition. Eli Lilly is developing efsitora alfa, a competing once-weekly basal insulin that could reach the market in the coming years. How the two drugs compare in efficacy, safety, and pricing will shape the evolution of this new insulin class.
Why It Matters
Insulin adherence remains a persistent challenge in diabetes care. Novo Nordisk noted in its announcement that Awiqli “may address challenges associated with the frequency of daily basal injections, by reducing them from seven to one per week.” The clinical review found that treatment compliance scores on the TRIM-D domain favored weekly dosing, suggesting that a less frequent injection schedule could improve adherence for patients who are unable or unwilling to maintain a daily regimen.
Awiqli is now approved in the United States, the European Union, and 13 additional countries, though market-specific indications vary. Its approval represents the culmination of more than a decade of development and positions once-weekly insulin as a viable alternative for patients who struggle with or prefer fewer injections.