FDA Approves Insulin Icodec (Awiqli) as First Once-Weekly Basal Insulin for Type 2 Diabetes

The US Food and Drug Administration (FDA) has approved Awiqli (insulin icodec-abae) injection 700 units/mL, the first and only once-weekly basal insulin available in the US, as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes (T2D).

The decision makes insulin icodec the first new class of basal insulin to reach US patients in more than 2 decades.

In July 2024, the FDA issued a Complete Response Letter (CRL) to Novo Nordisk for once-weekly basal insulin icodec, with requests concerning the manufacturing process and the type 1 diabetes (T1D) indication, which were required to be addressed before the BLA review could be completed. Importantly, the May 2024 FDA advisory committee vote of 7–4 against concluding that the benefits of insulin icodec outweigh its risks was specific to T1D; the committee did not evaluate its use for type 2 diabetes.

Novo Nordisk resubmitted the BLA in late September 2025, based on results from the ONWARDS type 2 diabetes phase 3A program, which comprised 5 randomized, active-controlled, treat-to-target clinical trials in approximately 4000 adults with T2D. Today's approval is the outcome of that resubmission, and it is limited to adults with T2D — a population where the clinical evidence was consistently robust throughout the regulatory review.

The ONWARDS Clinical Program

The approval rests on results from four of the ONWARDS trials: large, active-controlled, treat-to-target studies evaluating insulin icodec head-to-head against standard once-daily basal insulins, including insulin glargine U100 and insulin degludec.

ONWARDS 1, a 78-week trial in 984 insulin-naive adults with T2D and inadequate glycemic control, demonstrated a mean HbA1c reduction of –1.55% with once-weekly insulin icodec compared to –1.35% with once-daily insulin glargine U100.

ONWARDS 3 assessed insulin icodec against insulin degludec in combination with non-insulin antidiabetes treatments in insulin-naive adults with T2D, achieving a mean HbA1c reduction of –1.57% in the icodec group versus –1.36% in the degludec group at week 26.

ONWARDS 4, which evaluated icodec in combination with mealtime insulin in adults with T2D, demonstrated noninferiority to insulin glargine U100, with mean HbA1c reductions of –1.16% and –1.18%, respectively, at week 26.

ONWARDS 5, a 52-week real-world-design trial that utilized a dosing guide app for uptitration, demonstrated the largest separation from the comparator arm: a mean HbA1c reduction of –1.68% with insulin icodec versus –1.31% for once-daily basal insulin analogues.

Taken together, a published meta-analysis of the ONWARDS phase 3 program supports these findings. Across 5 randomized controlled trials enrolling 3764 participants, once-weekly insulin icodec demonstrated a statistically significant incremental HbA1c reduction compared to once-daily basal insulin analogues (mean difference, –0.17%; 95% CI, –0.28 to –0.06; P = .003), and a higher proportion of patients achieved HbA1c below 7% with icodec than with comparators (OR, 1.51; 95% CI, 1.14 – 1.99; P = .004).

In ONWARDS 1, insulin icodec allowed people to spend significantly more time in range compared with once-daily insulin glargine U100, with comparable time below range — a finding that ONWARDS principal investigator Julio Rosenstock, MD, Clinical Professor of Medicine at the University of Texas Southwestern Medical Center, described as demonstrating the potential to change how T2D requiring basal insulin is treated.

Managing Hypoglycemia

Prescribers should note that icodec's pharmacokinetic profile introduces a nuanced hypoglycemia consideration. Patients treated with Awiqli tended to have a greater incidence of hypoglycemic events, particularly on days 2 - 4 of the weekly dosing cycle, which corresponds to the pharmacokinetic profile for insulin icodec where exposure is highest early in the week.

In ONWARDS 3, combined level 2 or 3 hypoglycemia rates were statistically higher in the icodec group from week 0 to 26 (0.35 vs. 0.12 events per patient-year exposure; P = .01), though absolute rates were less than one event per patient-year in both arms.

This pattern was consistent across trials and should be incorporated into patient education, particularly for those at elevated hypoglycemia risk, such as older adults or those with renal impairment.

Patient and Physician Satisfaction Signal

Beyond glycemic efficacy, real-world uptake of a new insulin formulation often hinges on patient experience. In ONWARDS 2 and 5, patient treatment satisfaction was significantly higher with once-weekly icodec than with once-daily comparators, driven primarily by willingness to continue and recommend the therapy; in ONWARDS 2, 93.7% of icodec users preferred the once-weekly regimen, citing less frequent injections and ease of use.

Physician satisfaction data from ONWARDS 1 pointed in the same direction, with investigators more likely to recommend the weekly option.

"Research supports weekly injectable diabetes medications can be associated with improved patient adherence," said Rosenstock at the time. "Having a weekly basal insulin option like insulin icodec-abae may reshape insulin management in adults with type 2 diabetes, giving them a routine that feels more manageable as they work toward their blood sugar goals."

Awiqli is administered subcutaneously once weekly on the same calendar day each week using the Awiqli FlexTouch pen. The product is formulated at a concentration of 700 units/mL (U-700) — substantially more concentrated than standard U-100 formulations such as insulin glargine — and this distinction carries meaningful dosing error implications.

The prescribing information includes explicit warnings against using a syringe to withdraw insulin from the pen, dialing the maximum single dose of 700 units unless specifically prescribed, and mixing or diluting the product with any other insulin.

Common adverse effects include hypoglycemia, injection-site reactions, lipodystrophy, pruritus, rash, peripheral edema, and weight gain. Clinicians prescribing concomitant thiazolidinediones (TZDs) should counsel patients on the risk of fluid retention and potential worsening of heart failure.

Regulatory Context and Global Landscape

2026 has already proven to be an eventful year for diabetes pharmacotherapy. The 2026 ADA Standards of Care introduced new guidelines for GLP-1 usage, insulin pump access, and continuous glucose monitoring, promoting comprehensive diabetes management — a broader shift in which once-weekly basal insulin now fits as an additional tool for personalizing the treatment regimen.

Awiqli is expected to be available nationwide in US pharmacies in the coming months.

References

1. Novo Nordisk. Awiqli (insulin icodec-abae) [package insert]. Plainsboro, NJ: Novo Nordisk Inc.; 2026.
2. Novo Nordisk Resubmits Insulin Icodec (Awiqli) Injection BLA for Type 2 Diabetes. HCPLive. February 2026. https://www.hcplive.com/view/novo-nordisk-resubmits-insulin-icodec-awiqli-injection-bla-for-type-2-diabetes
3. FDA Issues Complete Response Letter for Once-Weekly Insulin Icodec. HCPLive. July 2024. https://www.hcplive.com/view/fda-issues-complete-response-letter-for-once-weekly-insulin-icodec
4. Once-Weekly Insulin Icodec Improves Time in Range, Glycemic Control Better than Daily Insulin Degludec. HCPLive. https://www.hcplive.com/view/once-weekly-insulin-icodec-improves-time-in-range-glycemic-control-better-than-daily-insulin-degludec
5. Rosenstock J, et al. Weekly icodec versus daily glargine U100 in type 2 diabetes without previous insulin. N Engl J Med. 2023;389(16):1533.
6. Philis-Tsimikas A, et al. Switching to once-weekly insulin icodec versus once-daily insulin degludec in basal insulin-treated type 2 diabetes (ONWARDS 2). Lancet Diabetes Endocrinol. 2023.
7. Lingvay I, et al. Once-weekly insulin icodec vs once-daily insulin degludec in adults with insulin-naive type 2 diabetes: the ONWARDS 3 randomized clinical trial. JAMA. 2023;330(3):228–237.
8. Mathieu C, et al. Switching to once-weekly insulin icodec versus once-daily insulin glargine U100 in basal-bolus insulin-treated type 2 diabetes (ONWARDS 4). Lancet. 2023.
9. American Diabetes Association Professional Practice Committee. Facilitating positive health behaviors and well-being to improve health outcomes: Standards of Care in Diabetes—2026. Diabetes Care. 2026;49(suppl 1):S89–S131.