The FDA has approved the first once-weekly basal analog insulin, Novo Nordisk’s icodec-abae (Awiqli injection 700 units/mL), for adults with type 2 diabetes (T2D).

The product is already approved in the EU and 13 other countries, including Canada, Australia, and Japan. In the US, the FDA issued the company a “complete response letter” in July 2024 to its first biologic license application for icodec for use in people with both major diabetes types, in part because of concerns regarding hypoglycemia risk in type 1 diabetes (T1D). In May 2024, an FDA advisory panel voted against its use in T1D while expressing no safety concerns about its use in T2D.

“Novo Nordisk finally agreed with the FDA to focus on T2D where it had the best data,” independent industry consultant Charles Alexander, MD, told Medscape Medical News, adding, “It definitely adds a convenient regimen for those with T2D who need insulin, especially for those who are also taking a once-weekly GLP-1 or dual [receptor agonist].”

Efficacy and Safety Data

The approval is based on data from Novo Nordisk’s four phase 3 ONWARDS trials, involving a total of 2680 adults with T2D not well controlled with other agents, comparing once-weekly icodec with daily basal insulin in combination with either mealtime insulin, a GLP-1 receptor agonist, or oral glucose-lowering drugs. These trials all showed either noninferiority or superiority of the once-weekly with the daily basal in glucose lowering.

In some of the trials, levels of hypoglycemia were numerically higher with icodec but not statistically significantly so. For example, in ONWARDS 1, rates of combined clinically significant or severe hypoglycemia events per person-year of exposure were 0.30 vs 0.16 for icodec vs glargine U100 at week 52 (estimated rate ratio, 1.64; 95% CI, 0.98-2.75).

Clinical Considerations

But the potential for hypoglycemia with once-weekly insulin in some patients with T2D still worries endocrinologist Anne L. Peters, MD, professor of clinical medicine at the University of Southern California, Los Angeles. “For those who are pretty sedentary and have type 2, this will be great because it will enhance adherence. But I have patients who are active and go out walking 4 days a week, so their insulin sensitivity and insulin requirements on a day-to-day basis can vary,” she told Medscape Medical News.

Another scenario of concern would be “if somebody goes from walking about and then they fall and break a hip or an ankle, and then become sedentary, and then go back….This drug is so long-acting it would be hard for me to adjust for that,” she said.

Baseline glycemic control would also make a difference in that people with higher A1c levels might be less prone to hypoglycemia than those with only mildly elevated values. Moreover, she pointed out that people recruited for clinical trials are counseled about lifestyle and thus may behave differently from those in the real world, and “you’re not going to get a nonadherent person into a study.”

Nonetheless, Peters said, “I’m actually eager to have it as part of my armamentarium, but it’s got to be individualized.” Patients initiated on once-weekly insulin must be educated about hypoglycemia and should ideally be using continuous glucose monitors, she said.

Peters also worries about cost and lack of insurance coverage, as is happening under Medicaid with GLP-1s. “There are states where you can’t get Ozempic or Mounjaro, even for those with diabetes. My patients who have trouble adhering would be the ones who benefit the most, but they’re the ones who are least likely to get an expensive new drug.”

Awiqli will be available nationwide in the US in the coming months, Novo Nordisk said in a statement.

Meanwhile, Eli Lilly is also developing a once-weekly basal insulin analog, efsitora alfa.

Alexander reported owning stock in Beta Bionics and consulting for Clario. Peters reported consulting for Vertex and Zucara Therapeutics and receiving research grants from Insulet Corporation.

Miriam E. Tucker is a freelance journalist based in the Washington, DC, area. She is a regular contributor to Medscape, with other work appearing in the Washington Post, NPR’s Shots blog, and Diatribe. She is on X @MiriamETucker and BlueSky @miriametucker.bsky.social.