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Weekly insulin found safe, effective for Type 2 diabetes

Phase 3 clinical trial led by UTSW researcher brings icodec injections one step closer to FDA approval

Senior man checking blood sugar levels
More than 37 million people in the United States, about 1 in 10, have diabetes. About 90%-95% of them have Type 2 diabetes, and a third of those require daily insulin injections to keep their glucose, or blood sugar, levels within a healthy range. (Photo credit: Getty Images)

DALLAS – July 12, 2023 – An experimental form of insulin administered just once a week was safe for patients with Type 2 diabetes and helped them maintain healthy blood sugar levels better than insulin injected daily, according to the results of a phase 3 clinical trial led by a UT Southwestern Medical Center researcher. The findings, published in JAMA, could move this potentially game-changing new drug, called insulin icodec, one step closer to approval by the Food and Drug Administration.

Ildiko Lingvay, M.D., M.P.H., M.S.C.S.
Ildiko Lingvay, M.D., M.P.H., M.S.C.S., is a Professor of Internal Medicine in the Peter O'Donnell Jr. School of Public Health at UT Southwestern.

“Insulin is the most burdensome therapy for people with diabetes,” said endocrinologist Ildiko Lingvay, M.D., M.P.H., M.S.C.S., Professor of Internal Medicine at UT Southwestern and its Peter O’Donnell Jr. School of Public Health. “A once-weekly version of the drug could minimize the stigma associated with daily insulin treatment, enabling more patients to start treatment when needed and stay on treatment to achieve the best possible glucose control and long-term outcomes.”

More than 37 million Americans – about 1 in 10 – have diabetes. About 90%-95% of them have Type 2 diabetes, in which the body does not respond normally to insulin, causing blood sugar (glucose) to become abnormally high. These levels can lead to long-term complications including heart disease, nerve damage, vision loss, and lower-extremity amputations.

About a third of people with Type 2 diabetes require insulin injections to keep their blood sugar within a healthy range, Dr. Lingvay explained. However, many resist due to the pain, inconvenience, and stigma of this treatment, leading to an average delay of three to five years for patients to start insulin when it is needed – a wait that can significantly worsen long-term outcomes.

Over the past several years, Dr. Lingvay and colleagues around the world have tested insulin icodec. Unlike the current daily insulin degludec, patients would inject insulin icodec once a week, relying on its interaction with a prevalent blood protein called albumin to slow icodec’s release into the bloodstream.

Dr. Lingvay and global colleagues have conducted five phase 3 clinical trials, called ONWARDS 1-5, to assess how icodec works in various clinical scenarios. For this ONWARDS 3 study, which Dr. Lingvay led, the research team treated 564 Type 2 diabetes patients from 92 clinics in 11 countries, including at UT Southwestern, who all required medications to lower their blood sugar but had never taken insulin.

The study used a rigorous double-blind randomized control trial. Specifically, the patients were randomized to one of two therapies: injected icodec once a week and a placebo daily, or injected degludec daily and a placebo once a week. The primary endpoint of the study was a change in a blood measure of longitudinal glucose control, namely hemoglobin A1C (HbA1C).

After 26 weeks of treatment and five weeks of follow-up, patients on weekly icodec had significantly larger improvements in their HbA1C than those using degludec daily.

Both groups had an extremely low rate of adverse events, Dr. Lingvay said, suggesting both forms of insulin are safe. Although the patients who received icodec had a slightly higher risk of low-blood sugar events, none of the events were severe enough to require emergency medical attention.

Dr. Lingvay participated in three other phase 3 trials testing icodec at UTSW and other sites. In ONWARDS 1 and ONWARDS 5, patients on icodec stayed in a healthy blood sugar range noticeably more often than patients on degludec. In ONWARDS 4, people treated with weekly insulin had similar improvement in glucose and similar occurrence of hypoglycemia compared with those on once-daily insulin.

Dr. Lingvay said the results suggest insulin icodec could be a significant innovation for patients with Type 2 diabetes if it is approved for clinical use. FDA evaluation is the next step.

“Patients in these clinical trials who learn they are taking insulin icodec tell us they are very disappointed when the trial ends and they have to switch to a daily insulin. Instead of just 52 injections a year, they must take 365,” Dr. Lingvay said. “Now we are one step closer to making insulin much easier for our patients to take.”

The ONWARDS trials were funded by the maker of insulin icodec, Novo Nordisk A/S. Dr. Lingvay is a consultant for the company.

About UT Southwestern Medical Center  
UT Southwestern, one of the nation’s premier academic medical centers, integrates pioneering biomedical research with exceptional clinical care and education. The institution’s faculty has received six Nobel Prizes, and includes 26 members of the National Academy of Sciences, 19 members of the National Academy of Medicine, and 14 Howard Hughes Medical Institute Investigators. The full-time faculty of more than 2,900 is responsible for groundbreaking medical advances and is committed to translating science-driven research quickly to new clinical treatments. UT Southwestern physicians provide care in more than 80 specialties to more than 100,000 hospitalized patients, more than 360,000 emergency room cases, and oversee nearly 4 million outpatient visits a year.