The novel once-weekly insulin analog efsitora alfa (efsitora) improved glucose control, compared to daily insulin, without a concomitant increase in severe hypoglycemia, across three phase 3 trials focused on people living with type 2 diabetes within the QWINT clinical program.

Findings from three QWINT studies were shared on Sunday, June 22, during the symposium, Advancing and Facilitating Basal Insulin Therapy in Type 2 Diabetes—Breaking News on the QWINT 1, 3, and 4 Trials with Once-Weekly Insulin Efsitora Alfa!  

“We are living in the most exciting time for type 2 diabetes therapy,” said Chantal Mathieu, MD, PhD, Professor of Endocrinology at Katholieke Universiteit Leuven, Belgium, and President of the European Association for the Study of Diabetes. “We have all these new therapies for type 2 diabetes, but insulin is still on this list. Until now, none of the drugs have been shown to protect against beta cell failure. So, most patients with type 2 diabetes will eventually need insulin treatment.”

With the new data from QWINT, efsitora is now the second long-acting, once-weekly insulin analog that has been evaluated in robust phase 3 studies and proven to be non-inferior to daily insulins. The other once-weekly insulin, icodec, was approved for use in both type 1 and 2 diabetes by the European Medicines Agency.

Richard M. Bergenstal, MD, Executive Director of the HealthPartners Institute International Diabetes Center, who provided an overview of efsitora and the QWINT program, highlighted the unmet need for effective insulin therapy that is not associated with an onerous injection burden.

Currently, basal insulin therapy requires once- or twice-daily injections. 

The frequency of insulin dosing is not the only challenge.

“Even with insulin therapy, only 23% of people with type 2 diabetes achieve a target HbA1c level <7%,” Dr. Bergenstal said.

He summarized the pharmacodynamic and pharmacokinetic properties of icodec and efsitora, highlighting their prolonged half-lives. He also differentiated their peak-to-trough ratios, which translate to a lower variability in glucose levels with efsitora over time.

The QWINT program included five treat-to-target randomized studies.

• QWINT-1 compared fixed-dose efsitora to insulin glargine over 52 weeks in insulin-naïve patients with type 2 diabetes.
• QWINT-2, also focused on insulin-naïve patients, compared flexible efsitora dosing to degludec over 52 weeks.
• QWINT-3 was a basal insulin switch study of flexible efsitora dosing, compared with degludec, over 78 weeks.
• QWINT-4, focused on individuals with type 2 diabetes on basal and mealtime insulin therapy, compared flexible efsitora dosing to insulin glargine over 26 weeks.
• The only study focused on individuals with type 1 diabetes, QWINT-5, compared flexible efsitora dosing to degludec over 52 weeks.

Findings from QWINT-2 and QWINT-5 were published in 2024.

Across the three QWINT studies discussed at the symposium, efsitora met the primary endpoint—non-inferiority to the comparator in inducing glycemic control, as measured by change in A1C from baseline to week 26 (QWINT-3 and QWINT-4) or week 52 (QWINT-1).

Importantly, efsitora-induced glycemic management improvements occurred without an accompanying increase in incidence of combined level 2 and 3 (moderate to severe) hypoglycemia. The low incidence of hypoglycemia with the once-weekly efsitora was comparable to that with daily insulin comparators in QWINT-1, QWINT-3, and QWINT-4.

These “impressive and incredibly low number of hypoglycemia events” translated to <1 event per participant per year in both groups, according to Athena Philis-Tsimikas, MD, Vice President of the Scripps Whittier Diabetes Institute and Director of Community Engagement, Clinical Translational Science, Scripps Research Translational Institute, who discussed QWINT-3 findings.

Dr. Mathieu said clinicians have long considered severe hypoglycemia to be a major, and potentially life-threatening, concern associated with longer-acting insulins. However, the QWINT program, along with the ONWARDS program of icodec, have shown that once-weekly insulin dosing is possible without increasing risk of severe hypoglycemia in people with type 2 diabetes.

She pointed out that in both QWINT and ONWARDS, hypoglycemia incidence was higher with the once-weekly insulins, compared to the comparators, in individuals with type 1 diabetes. People with type 1 diabetes may need more nuanced insulin dosing throughout the day to manage their glycemic status, a concept also reflected in the wide range of insulin throughout the day in this population, based on automated insulin delivery metrics.

The QWINT studies did not demonstrate superiority of efsitora over the comparators in terms of efficacy in improving glycemic control, a key secondary outcome.

Julio Rosenstock, MD, Senior Scientific Advisor for Velocity Clinical Research, Director of Velocity’s site at Medical City Dallas, and Clinical Professor of Medicine at the University of Texas Southwestern Medical Center, pointed out the unique and innovative fixed-dose titration scheme used in QWINT-1, in which doses of efsitora were sequentially escalated in patients who did achieve the glycemic target (fasting blood glucose between 80 to 130 mg/dL) over four-week periods, culminating in flexible efsitora dosing.

Each of the QWINT studies also assessed patient-reported outcomes with once-weekly insulin dosing.

Thomas Blevins, MD, founder of Texas Diabetes and Endocrinology, who discussed QWINT-4 results, shared data from the patient-reported basal insulin experience questionnaire. Among efsitora-treated patients, 93% preferred or strongly preferred efsitora to their pre-study daily basal insulin, and 82% were likely or very likely to incorporate efsitora into their routine.

Similarly, in QWINT-3, efsitora-treated participants reported significantly higher treatment satisfaction than the degludec group. Dr. Philis-Tsimikas shared the following feedback from a patient in the study: “I’m all for results. Lasting a full week without needing another shot made a difference for me. I was able to better manage my numbers without having to think about it.”

Findings from the QWINT-1, QWINT-3, and QWINT-4 studies were published concurrent with the symposium.

On-demand access to presentations from the 85^th Scientific Session will be available to registered participants following the conclusion of the meeting in Chicago, from June 25–August 25.