Introduction & Objective: Efsitora is an insulin receptor agonist designed to have a flat pharmacokinetic profile and long half-life enabling weekly dosing. While these features may provide stable glucose levels, their impact on hypo risk is less clear. A phase 1 study was conducted to assess hypo risk using controlled, experimental conditions that mimic hypo risk situations that may be encountered in daily life.

Methods: This single-site, open-label, 2-period, fixed-sequence (glargine-efsitora) study was conducted in 54 participants with T2D previously on basal insulin (BMI 21.8-39.7 kg/m2, HbA1c 6.5-9.4%). After titration to stable fasting glucose (FG) with glargine or efsitora, the incidence of hypo was assessed during 3 test conditions: prolonged fasting 24-hrs (PF), PF with exercise (EX), and after receiving a double dose (DD) of study insulin.

Results: Mean FG at start of tests was 6 mg/dL lower with PF and EX and 10 mg/dL lower with DD in the efsitora group compared to glargine. Incidence of Level 1 hypo (≥54 to <70 mg/dL) was not significantly different under any test condition: incidence efsitora vs glargine, difference in proportion (95%CI) for PF: 44.7 vs 42.6%, 2.1 (-17.2, 21.4); EX: 65.9 vs 50.0%, 15.9 (-3.0, 34.8); DD: 68.1 vs 61.7%, 6.4 (-12.8, 25.6). Level 1 hypo resolved spontaneously or after 15g oral glucose. Level 2 (<54 mg/dL) was infrequent in both treatments and all test conditions. No severe hypo occurred in this study. Mean nadir glucose for hypo was similar between treatments and test conditions ranging from 62.8-66.3 mg/dL. Duration of hypo events was also similar between treatments ranging from 76.6 to 115.2 mins depending on the test condition.

Conclusion: Once weekly efsitora did not increase the incidence, duration, or severity of hypo compared to once daily glargine during periods of provocation in patients with T2D.

Disclosure

T. Heise: Research Support; ADOCIA, AstraZeneca, Biocon, Crinetics Pharmaceuticals, Inc., Eli Lilly and Company, Genova, Novo Nordisk A/S. Consultant; Gan&Lee Pharmaceuticals. Speaker's Bureau; Eli Lilly and Company. Research Support; Altimmune Inc., Sanofi, Zealand Pharma A/S, BIOTON, Civica Foundation, Enyo Pharma, Gan&Lee Pharmaceuticals, Nanexa AB, SamChunDang Pharm. Co. G. Andersen: Employee; Profil Institut für Stoffwechselforschung GmbH. E.J. Pratt: Employee; Eli Lilly and Company. Stock/Shareholder; Eli Lilly and Company. J. Leohr: None. T. Fukuda: Employee; Eli Lilly and Company. Q. Wang: Employee; Eli Lilly and Company. C.M. Kazda: Employee; Eli Lilly and Company. J.M. Bue-Valleskey: Employee; Eli Lilly and Company. R.M. Bergenstal: Other Relationship; Abbott. Research Support; Arkray Marketing. Consultant; Ascensia Diabetes Care, Bigfoot Biomedical, Inc., CeQur. Other Relationship; Dexcom, Inc., Eli Lilly and Company. Consultant; embecta, Hygieia. Research Support; Insulet Corporation. Consultant; MannKind Corporation. Other Relationship; Medtronic, Novo Nordisk. Consultant; Onduo LLC, Roche Diabetes Care. Other Relationship; Sanofi. Research Support; Tandem Diabetes Care, Inc. Other Relationship; UnitedHealth Group. Consultant; Vertex Pharmaceuticals Incorporated, Zealand Pharma A/S.

Funding

This research was funded by Eli Lilly and Company.

© 2024 by the American Diabetes Association
2024
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