insulin efsitora alfa (LY3209590) / Eli Lilly - LARVOL DELTA

Novel Once-Weekly Basal Insulin Efsitora Alfa Versus Once-Daily Insulin Degludec in Adults With Diabetes Mellitus: A Systematic Review and Meta-Analysis (ENDO 2025) - "This meta-analysis demonstrates that once-weekly insulin efsitora is noninferior to once-daily insulin degludec in achieving glycemic control in adults with diabetes. Both treatments resulted in comparable reductions in HbA1c and showed no significant differences in the rates of moderate or severe hypoglycemia. These findings indicate that insulin efsitora may serve as a viable alternative to daily basal insulin regimens, potentially enhancing patient adherence through a once-weekly dosing schedule."

Retrospective data • Review • Diabetes • Metabolic Disorders • Severe Hypoglycemia • Type 2 Diabetes Mellitus

Weekly insulin efsitora alfa vs daily insulin glargine in adults with type 2 diabetes treated with basal and bolus insulin: QWINT-4 (EASD 2025) - P3 | "In adults with T2D treated with basal and bolus insulin, efsitora demonstrated noninferior HbA1c reductions and similar rates of hypoglycaemia vs glargine."

Clinical • Diabetes • Metabolic Disorders • Severe Hypoglycemia • Type 2 Diabetes Mellitus

Weekly insulin efsitora alfa in adults with type 2 diabetes treated with basal insulin (QWINT-3) (EASD 2025) - P3 | "Clinical Trial Registration Number: NCT05275400 Background and aims: Basal insulin plays a key role in T2D treatment, but there is a substantial burden with daily injections. In adults with T2D treated with basal insulin, efsitora demonstrated noninferiority to degludec in HbA1c reduction at 26 weeks, which was maintained to 78 weeks of treatment. Both efistora and degludec-treated participants achieved increased TIR by 2 hours with similarly low rates of hypoglycaemia."

Clinical • Diabetes • Hypoglycemia • Metabolic Disorders • Type 2 Diabetes Mellitus

Fixed-dose titration of insulin efsitora alfa demonstrates greater patient preference vs daily glargine in insulin naive adults with type 2 diabetes in QWINT-1 (EASD 2025) - P3 | "In insulin naïve adults with T2D, efsitora improved health outcomes across a variety of domains and reduced treatment burden. More participants receiving efsitora vs glargine indicated that they were "very likely" to use their study treatment."

Clinical • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

Characteristics and glycaemic outcomes of insulin naive adults with type 2 diabetes treated with an innovative fixed-dose regimen of weekly insulin efsitora in QWINT-1 (EASD 2025) - P3 | "Supported by Eli Lilly and Company Clinical Trial Registration Number: NCT05662332 Background and aims: QWINT-1 evaluated innovative fixed-dose titration of weekly insulin efsitora alfa (efsitora) vs daily glargine U100 over 52 wks in 795 insulin naïve adults with type 2 diabetes (T2D)... In QWINT-1, trends in certain characteristics were as expected: those requiring higher doses had greater baseline BMI and glycemic measures. HbA1c reductions were similar across efsitora doses compared to glargine at wk 52. Fixed-dose titration, including escalation to higher doses, did not increase the clinically significant hypoglycemia rate."

Clinical • Diabetes • Hypoglycemia • Metabolic Disorders • Type 2 Diabetes Mellitus

Innovative fixed-dose titration of weekly insulin efsitora alfa using a single-dose pen vs daily glargine to facilitate insulin therapy in type 2 diabetes: the QWINT-1 phase 3 trial (EASD 2025) - P3 | "In insulin-naïve adults with T2D, fixed-dose titration of QW efsitora had similar mean HbA1c reductions to 7%, with lower rates of clinically meaningful hypoglycemia, compared to QD glargine. This simple fixed-dose regimen for QW efsitora could facilitate insulin treatment and reduce injection burden compared to traditional titration of QD insulins."

P3 data • Diabetes • Hypoglycemia • Metabolic Disorders • Type 2 Diabetes Mellitus

Insulin efsitora alfa (efsitora) demonstrates better overall health state vs daily degludec in insulin naive adults with type 2 diabetes in QWINT-2 (EASD 2025) - P3 | "Weekly efsitora treatment resulted in a better overall health state, easier management, and reduced treatment burden vs daily degludec in insulin-naïve adults with T2D, with a greater simplicity perception by the participants. These findings may reduce insulin initiation inertia and delays in T2D management."

Clinical • Diabetes • Hypoglycemia • Metabolic Disorders • Type 2 Diabetes Mellitus

Insulin efsitora alfa (efsitora) demonstrates better overall health state vs daily degludec in basal switch adults with type 2 diabetes in QWINT-3 (EASD 2025) - P3 | "Treatment with weekly efsitora resulted in greater tx satisfaction, better overall health state, and reduced tx burden vs degludec in adults with T2D currently treated with basal insulin. Greater satisfaction and perceived improved overall health state may improve adherence and clinical outcomes."

Clinical • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

Once-weekly basal insulin therapy in type 1 diabetes: A paradigm shift or a work in progress? (PubMed, Am J Health Syst Pharm) - "Once-weekly basal insulin represents a potential paradigm shift in T1DM management, offering convenience but presenting challenges related to hypoglycemia risk, patient acceptance, and regulatory hurdles. Further research is needed to refine titration protocols, identify optimal patient populations, and address safety concerns before these therapies can become standard of care."

Journal • Diabetes • Hypoglycemia • Metabolic Disorders • Type 1 Diabetes Mellitus • IR

Once-weekly insulin efsitora alfa versus once-daily insulin degludec in adults with type 2 diabetes currently treated with basal insulin (QWINT-3): a phase 3, randomised, non-inferiority trial. (PubMed, Lancet) - P3 | "Efsitora is a well tolerated and efficacious once-weekly alternative to daily basal insulin, with a reduced injection frequency, for the treatment of adults with type 2 diabetes."

Head-to-Head • Journal • P3 data • Cardiovascular • Diabetes • Hypoglycemia • Metabolic Disorders • Type 2 Diabetes Mellitus

Once-weekly insulin efsitora alfa versus once-daily insulin glargine U100 in adults with type 2 diabetes treated with basal and prandial insulin (QWINT-4): a phase 3, randomised, non-inferiority trial. (PubMed, Lancet) - P3 | "Efsitora showed non-inferior HbA1c reductions and similar rates of combined clinically significant or severe hypoglycaemia versus glargine U100 in participants with type 2 diabetes treated with basal and prandial insulin. These findings show that efsitora is a well tolerated and efficacious once-weekly alternative to daily basal insulin, with a reduced injection frequency, for the treatment of adults with type 2 diabetes."

Head-to-Head • Journal • P3 data • Diabetes • Metabolic Disorders • Severe Hypoglycemia • Type 2 Diabetes Mellitus

Treatment Experience of People with Type 2 Diabetes Using Once-Weekly Efsitora in QWINT Phase 3 Trials—A Qualitative Study (ADA 2025) - "PwT2D were interviewed about their experience and willingness to take an innovative weekly basal insulin to better understand the potential of once-weekly insulin efsitora alfa in addressing the burdens associated with insulin treatment. Primary objective was to explore PwT2D experiences with once-weekly efsitora... Once-weekly basal insulin may reduce the complexity of insulin therapy by being easy to use, convenient, and flexible. The majority of PwT2D, especially those who are IE with a daily insulin, were "definitely willing" to continue with weekly basal insulin which may result in improved experiences with insulin therapy and outcomes for PwT2D."

Late-breaking abstract • P3 data • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

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! (ADA 2025) - No abstract available

Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

Fixed-Dose Titration of Insulin Efsitora Alfa Demonstrates Greater Patient Preference vs. Daily Glargine in Insulin-Naïve Adults with T2D in QWINT-1 (ADA 2025) - "In insulin naïve adults with T2D, efsitora improved health outcomes across a variety of domains and reduced treatment burden. More participants receiving efsitora vs glargine indicated that they were "very likely" to use their study treatment."

Clinical • Metabolic Disorders • Type 2 Diabetes Mellitus

Insulin Efsitora Alfa (Efsitora) Demonstrates Better Overall Health State vs. Daily Degludec in Insulin-Naive Adults with T2D in QWINT-2 (ADA 2025) - "Weekly efsitora treatment resulted in a better overall health state, easier management, and reduced treatment burden vs daily degludec in insulin-naïve adults with T2D, with a greater simplicity perception by the participants. These findings may reduce insulin initiation inertia and delays in T2D management."

Clinical • Hypoglycemia • Metabolic Disorders • Type 2 Diabetes Mellitus

Insulin Efsitora Alfa (Efsitora) Demonstrates Better Overall Health State vs. Daily Degludec in Basal-Switch Adults with T2D in QWINT-3 (ADA 2025) - "Treatment with weekly efsitora resulted in greater tx satisfaction, better overall health state, and reduced tx burden vs degludec in adults with T2D currently treated with basal insulin. Greater satisfaction and perceived improved overall health state may improve adherence and clinical outcomes."

Clinical • Metabolic Disorders • Type 2 Diabetes Mellitus

Insulin Efsitora Alfa vs. Insulin Degludec in Adults with Insulin-Naïve T2D (QWINT-2)—A Japan Subgroup Analysis (ADA 2025) - P3 | "Once-weekly efsitora was comparable to once-daily degludec in reducing HbA1c in insulin-naïve Japan participants with T2D. Efficacy and safety were consistent with the overall study population."

Clinical • Hypoglycemia • Metabolic Disorders • Type 2 Diabetes Mellitus

Steady-State Pharmacokinetics and Glucodynamics of Once-Weekly Insulin Efsitora Alfa (Efsitora) in Individuals with Type 2 Diabetes (T2D) (ADA 2025) - "After a lead-in period with once-daily degludec for dose-finding, eligible participants received a one-time starting dose of 12 U/kg efsitora and weekly doses of 4 U/kg for 9 weeks. Efsitora demonstrated a flat and prolonged PK profile providing a constant level of insulin and as a result a stable glucose lowering response across the weekly dosing interval."

Clinical • PK/PD data • Diabetes • Metabolic Disorders • Type 2 Diabetes Mellitus

Bioequivalence of Insulin Efsitora Alfa (Efsitora) U-500 and U-1000 Formulations (ADA 2025) - P1 | "This study demonstrated that U-500 and U-1000 efsitora formulations were BE, supporting the ability of patients to transfer between U-500 and U-1000 in a 1:1 unit conversion."

Diabetes • Metabolic Disorders

Weekly Fixed-Dose Insulin Efsitora in Type 2 Diabetes without Previous Insulin Therapy. (PubMed, N Engl J Med) - P3 | "In adults with type 2 diabetes who had not previously received insulin, once-weekly efsitora, administered in a fixed-dose regimen, was noninferior to once-daily glargine in reducing glycated hemoglobin levels. (Funded by Eli Lilly; ClinicalTrials.gov number, NCT05662332.)."

Journal • Diabetes • Metabolic Disorders • Severe Hypoglycemia • Type 2 Diabetes Mellitus

Lilly's once-weekly insulin efsitora alfa demonstrated A1C reduction and a safety profile consistent with daily insulin in multiple Phase 3 trials (Eli Lilly Press Release) - P3 | N=795 | QWINT-1(NCT05662332) | P3 | N=986 | QWINT-3 (NCT05275400) | P3 | N=730 | QWINT-4 (NCT05462756) | Sponsor: Eli Lilly and Company | "In QWINT-1, efsitora reduced A1C by 1.31% compared to 1.27% for insulin glargine at week 52 for the efficacy estimand. In the trial, efsitora was titrated to four fixed doses at four-week intervals, as needed for blood glucose control. In QWINT-3, efsitora reduced A1C by 0.86% compared to 0.75% for insulin degludec at week 26 for the efficacy estimand. In QWINT-4, efsitora reduced A1C by 1.07% compared to 1.07% for insulin glargine at week 26 for the efficacy estimand. In these two trials, efsitora was administered using traditional insulin dosing with adjustments based on each patient's glucose level...Across the three trials, efsitora demonstrated an overall safety profile similar to two of the most commonly used daily basal insulin therapies for the treatment of type 2 diabetes."

P3 data • Type 2 Diabetes Mellitus

Continuous Glucose Monitoring and Hypoglycaemia Metrics With Once-Weekly Basal Insulin Fc Versus Insulin Degludec: A Systematic Review and Meta-Analysis. (PubMed, Endocrinol Diabetes Metab) - "Once-weekly BIF provides similar overall glycaemic control to insulin degludec but with increased time in mild hypoglycaemia and higher event rates of clinically significant and severe hypoglycaemia. These findings highlight the need for individualised dosing and monitoring when transitioning to weekly insulin regimens."

Clinical • Journal • Retrospective data • Review • Diabetes • Hypoglycemia • Metabolic Disorders • Severe Hypoglycemia • Type 2 Diabetes Mellitus

Effects of Insulin Efsitora Alfa (EfSitora) on Frequency and Severity of Hypoglycemia (Hypo) Under Conditions of Increased Hypo Risk Compared to Glargine in Type 2 Diabetes (T2D) (DDG 2025) - "Once Weekly Efsitora Did not Increas the Incidence, Duration, Or Severity of Hypo Compared to Once Daily Glargine During Periods of Provocation in Patients with T2d. ^ Denotes Square Root of in This Abstract"

Diabetes • Hypoglycemia • Metabolic Disorders • Type 2 Diabetes Mellitus

Safety and Functionality of a Novel Clinical Decision-Support Algorithm with Insulin Efsitora Alfa in Adults with Type 2 Diabetes: Early Feasibility Study. (PubMed, Diabetes Technol Ther) - "No level 3 hypoglycemia was observed. The novel CDS algorithm showed promising clinical performance and favorable investigator confidence as determined by a low rate of dose overrides."

Journal • Diabetes • Hypoglycemia • Metabolic Disorders • Type 2 Diabetes Mellitus • IR

Once-weekly Basal Insulin Fc versus daily insulin degludec for glycemic control in diabetes: a systematic review, meta-analysis, and meta-regression. (PubMed, J Diabetes Metab Disord) - "However, increased hypoglycemia risks in certain subgroups and higher adverse event rates warrant further evaluation. The online version contains supplementary material available at 10.1007/s40200-025-01602-y."

Journal • Retrospective data • Review • Diabetes • Hypoglycemia • Metabolic Disorders • Pain • Type 1 Diabetes Mellitus • Type 2 Diabetes Mellitus