Michael Monostra , 2025-06-22 21:44:00
Key takeaways:
- Insulin efsitora was noninferior to once-daily insulins in three randomized controlled trials.
- Rates of level 2 and level 3 hypoglycemia were not higher with efsitora vs. once-daily insulins.
CHICAGO — A once-weekly basal insulin conferred similar HbA1c to once-daily insulins among adults with type 2 diabetes, both in previous basal insulin users and first-time insulin users, according to data from the QWINT trials.
At the American Diabetes Association Scientific Sessions, researchers presented findings from the QWINT-1, QWINT-3 and QWINT-4 trials, which assessed once-weekly insulin efsitora (Eli Lilly) in three different patient populations. Researchers compared insulin efsitora with once-daily insulin glargine in QWINT-1 and QWINT-4 and once-daily insulin degludec (Novo Nordisk) in QWINT-3. In all three trials, insulin efsitora met the primary endpoint, inducing noninferior HbA1c reductions compared with once-daily insulins, with the noninferiority margin being an HbA1c difference of 0.4 percentage points or less.
Findings from three QWINT trials showed once-weekly insulin efsitora was noninferior to once-daily insulins in adults with type 2 diabetes.
Julio Rosenstock, MD, FACE, 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, highlighted the difficulty of titrating once-daily insulin for patients, which can lead to nonadherence to therapy or delays in initiating treatment. Rosenstock said insulin efsitora could help simplify insulin initiation and treatment.
Julio Rosenstock
“We’re very familiar with the single fixed dosing that has been widely used, accepted and increasingly utilized very successfully with [incretin-based] therapies,” Rosenstock said during a press conference. “You can imagine that if we can do the same with weekly insulin, that may become a real game changer.”
QWINT-1
The QWINT-1 trial enrolled 795 adults with type 2 diabetes who did not previously use insulin (49.9% women; mean age, 56.3 years). Participants were randomly assigned, 1:1, to once-weekly insulin efsitora or daily 100 U insulin glargine for 1 year. Those assigned insulin efsitora started at 100 U per week with dose adjustments made to achieve a fasting blood glucose between 80 mg/dL and 130 mg/dL. If adults had a glucose of more than 130 mg/dL after reaching a fixed dose of 400 U insulin efsitora, they transitioned to variable dosing.
Adults assigned insulin efsitora had an HbA1c decrease from 8.2% at baseline to 7.05% at 1 year, and the insulin glargine group had an HbA1c decline from 8.28% at baseline to 7.08% at 1 year. The HbA1c decline with insulin efsitora was noninferior compared with glargine (estimated treatment difference, –0.03 percentage points; 95% CI, –0.18 to 0.12; P for noninferiority = .68).
An HbA1c of less than 7% was achieved by 57% of the insulin efsitora group and 52% of the insulin glargine group at 1 year. Mean fasting glucose was 127.7 mg/dL and 126.7, respectively, at 1 year. Adults assigned insulin efsitora had a lower mean total weekly insulin dose at 1 year (289.1 U/week vs. 332.8 U/week).
The insulin efsitora group had lower rates of level 2 hypoglycemia, with glucose of less than 54 mg/dL, or level 3 hypoglycemia, in which assistance was required for treatment, than the insulin glargine group (estimated RR = 0.57; 95% CI, 0.39-0.84). Forty-one percent of the insulin efsitora group and 33% of the insulin glargine group achieved an HbA1c of less than 7% without experiencing a level 2 or level 3 hypoglycemia event.
Adverse events occurred in 59.9% of the insulin efsitora group and 65.1% of the insulin glargine group. Severe adverse events were reported by 6.5% and 5.3%, respectively.
Rosenstock said it was reassuring to see that once-weekly insulin did not lead to higher rates of hypoglycemia compared with a once-daily therapy.
“In terms of the adverse event profile, we didn’t see any signal, nothing to be concerned about,” Rosenstock said.
Rosenstock added that 76% of adults in the insulin efsitora group were able to remain on a fixed dose to maintain glycemic control by the end of the trial.
“I think this can substantially facilitate and simplify initiating and escalating insulin therapy, potentially changing the management paradigm in type 2 diabetes,” Rosenstock said.
QWINT-3
In QWINT-3, 986 adults with type 2 diabetes who were using basal insulin and up to three glucose-lowering drugs at baseline without prandial insulin were enrolled (median age, 62 years; 44% women). The study group was randomly assigned, 2:1, to once-weekly insulin efsitora or once-daily insulin degludec for 78 weeks. The primary endpoint was noninferiority in HbA1c between the two groups at 26 weeks.
In the treatment-regimen estimand, HbA1c declined from 7.8% at baseline to 6.99% at 26 weeks for adults receiving insulin efsitora. The insulin degludec group had an HbA1c decline from 7.79% at baseline to 7.08% at 26 weeks. The insulin efsitora group had a 0.09 percentage point greater decline in HbA1c than the insulin degludec group, meeting the study’s 0.4 percentage point noninferiority margin.
At 52 weeks, the insulin efsitora group had a greater HbA1c decrease than the insulin degludec group (estimated treatment difference; –0.19 percentage points, 95% CI, –0.3 to –0.07; P = .0014). The two groups had a similar change in HbA1c at 78 weeks.
Athena Philis-Tsimikas
Change in FBG was similar at 26 weeks between the two groups. In the 4 weeks before week 26, both groups had a similar time in range as measured by continuous glucose monitoring, with a 62.8% time in range for those assigned insulin efsitora and 61.3% for those assigned insulin degludec. Time above range did not differ between the groups. Adults assigned insulin efsitora had a 0.14 percentage point higher time below range than those assigned insulin glargine (P = .04).
Rates of level 2 and level 3 hypoglycemia were not significantly different between the two groups, occurring in 41% of adults assigned insulin efsitora and 37% assigned insulin degludec. Nocturnal level 2 and level 3 hypoglycemia rates were deemed to be low, with 0.11 events per patient-year of exposure in the insulin efsitora group and 0.1 events per patient-year with insulin degludec. At 78 weeks, level 1 hypoglycemia occurred more frequently with insulin efsitora than insulin glargine (8.34 events per patient-year vs. 6.05 events per patient-year).
Treatment-emergent adverse events occurred in a higher percentage of adults assigned insulin efsitora vs. degludec (75% vs. 66%). The proportion of adults with serious adverse events was not significantly different between the two groups.
Athena Philis-Tsimikas, MD, corporate vice president of Scripps Whittier Diabetes Institute in San Diego, said the insulin efsitora group had significantly higher treatment satisfactions scores at 26, 52 and 78 weeks than the insulin degludec group.
“We have an amazing number of new medications, but insulin will always remain relevant,” Tsimikas said during a presentation. “We will need it for our patients. So, I’m very happy that we continue to have innovations in the types of insulin that can be offered.”
QWINT-4
The QWINT-4 study population included 730 adults with type 2 diabetes previously treated with basal insulin who received at least two prandial insulin injections per day at baseline (51% women; mean age, 58.9 years). Participants were randomly assigned, 1:1, to insulin efsitora or 100 U once-daily insulin glargine for 26 weeks.
Thomas Blevins
In the treatment-regimen estimand, both groups had a baseline HbA1c of 8.18%. At 26 weeks, adults assigned insulin efsitora had a mean 7.17% HbA1c compared with a 7.18% HbA1c for the glargine group (estimated treatment difference; –0.01 percentage points; 95% CI, –0.14 to 0.12), meeting the trial’s noninferiority endpoint. There was no difference in the percentage of adults achieving an HbA1c of less than 7% without level 2 or level 3 hypoglycemia.
Time in range was similar between the two groups. From 6 a.m. to midnight, adults assigned insulin efsitora had a higher time in range than those assigned insulin glargine.
Total weekly insulin dose was lower with insulin efsitora (592.9 U/week vs. 666.4 U/week; P < .0001). Basal weekly insulin dose was also lower with insulin efsitora (391.6 U/week vs. 426.6 U/week; P = .0008).
Level 2 and level 3 hypoglycemia occurred in 56% of participants in each group. Five severe hypoglycemia episodes were reported in each group. Adults assigned insulin efsitora had a higher rate of level 1 hypoglycemia than the insulin glargine group (estimated RR= 1.33; 95% CI, 1.13-1.55). Nocturnal level 1 hypoglycemia rates were lower with insulin efsitora than glargine (estimated RR = 0.75; 95% CI, 0.57-0.98).
“The incidence of hypoglycemia in all of these different categories [combined] was similar between the two ,” Thomas Blevins, MD, FACE, a clinical endocrinologist at Texas Diabetes and Endocrinology in Austin, said during the presentation.
Adverse events occurred in 54% of the insulin efsitora group and 52% of the insulin glargine group. Nasopharyngitis and urinary tract infection were the two most common treatment-emergent adverse events in both groups. No cases of diabetic ketoacidosis were reported.
Considerations for clinical care
Insulin efsitora is not the only once-weekly insulin currently in development. As Healio previously reported, once-weekly insulin icodec (Novo Nordisk) conferred a long-term HbA1c reduction for adults with type 2 diabetes in the ONWARDS 1 trial.
Chantal Mathieu, MD, PhD, professor of medicine and chair of endocrinology at the University Hospital Gasthuisberg Leuven in Belgium, said it will be important for health care professionals to understand the profiles of both once-weekly insulins if the FDA approves them.
Chantal Mathieu
“Icodec has a half-life of 8 days and … there is some variation at the end of the injection,” Mathieu said during the presentation. “Efsitora has a half-life of 19 days with a more flat profile. These very long half-lives also mean when you initiate these insulins, they take some time to reach the plateau.”
Mathieu said she feels that once-weekly insulins will lead to a paradigm shift in the management of type 2 diabetes.
“It is obvious that we are now living in exciting times with all of these therapies that we have for people with type 2 diabetes,” Mathieu said. “But insulin is still there.”
References:
Perspective
This is quite exciting and particularly relevant for patients with type 2 diabetes.
For type 1 diabetes, the technologies that we have managed to develop, with automated insulin delivery that is precise, a very small patient population with type 1 diabetes will be candidates for weekly insulin. But for people with type 2 diabetes who cannot achieve glucose control with other agents, the ease of combining, for instance, a GLP-1, with weekly insulin, is probably extremely rare, Quality of life for our patients, glucose control, less weight gain are all important components, especially if the risk for hypoglycemia is also mitigated. I think that for type 2 diabetes, it has a very high relevance and impact for care at large.
Rodica Pop-Busui, MD, PhD
Disclosures: Pop-Busui reports receiving funding from Breakthrough T1D and the NIH; and serving as a consultant for Lexicon and Roche.
Sources/Disclosures
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Bergenstal RM, et al. 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. Presented at: American Diabetes Association Scientific Sessions; June 20-23, 2025; Chicago.
Disclosures:
Blevins reports receiving research support from Abbott, Dexcom, Eli Lilly, MannKind, Medtronic, Novo Nordisk, Tandem Diabetes Care and ViaCyte; and speaking for AstraZeneca, Boehringer Ingelheim, Dexcom, Eli Lilly and Novo Nordisk. Mathieu reports advising for Abbott, Bayer, Biomea Fusion, Eli Lilly, Novo Nordisk, Roche, SAB Biotherapeutics, Sanofi and Vertex Pharmaceuticals. Philis-Tsimikas reports performing research and advising on behalf of her employer for AbbVie, Dexcom, Eli Lilly, Medtronic, Novo Nordisk and Sanofi. Rosenstock reports receiving grants from Amgen, Applied Therapeutics, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Hanmi Pharmaceutical, Intarcia Novartis, Novo Nordisk, Oramed, Pfizer, Regeneron Roche, Sanofi and Terns; consulting for Amgen, Applied Therapeutics, Biomea Fusion, Boehringer Ingelheim, Corcept, Eli Lilly, Hanmi Pharmaceutical, Intarcia, Novo Nordisk, Oramed, Regeneron, Regor Pharmaceuticals, Roche, Sanofi, Structure Therapeutics, Terns and Zealand; and receiving travel support from Applied Therapeutics, Boehringer Ingelheim, Intarcia, Novo Nordisk, Oramed and Sanofi.
