BIF is a fusion protein combining a novel single chain insulin variant with a human IgG Fc domain. The safety population from 3 randomized, open-label, phase 2 treat-to-target studies included 942 people with T2D previously treated with basal insulin (T2D-Switch) or new to insulin therapy (T2D-Naïve), or with T1D on multiple daily injections (T1D). QW BIF was compared to once daily (OD) DEG for 26 or 32 wks. Given BIF's slow accumulation and extended PK profile, initiation of or transition from prior OD basal insulin to BIF was managed by “boosting” initial exposure with a one-time ~ 3-fold LD strategy to achieve therapeutic concentration more quickly. In the absence of a definitive mg to unit conversion factor, determination of the starting QW dose differed by study and was based on PK/PD modelling and individual patient characteristics. Fasting glucose and patient reported hypoglycemia <70 mg/dL were compared during the first 6 wks of treatment and showed no clinically significant differences between treatments (Table). T2D-Switch and T1D studies included CGM and data during first 6 wks of the study were reviewed; no severe hypoglycemia was reported during this time. These data suggest that the BIF LD strategy is safe and effective in reducing transient hyperglycemia, especially in T2D. Disclosure J.M.Bue-valleskey: Employee; Eli Lilly and Company. C.M.Kazda: Employee; Eli Lilly and Company. Q.Zhang: Employee; Eli Lilly and Company, Stock/Shareholder; Eli Lilly and Company. A.Haupt: Employee; Lilly, Stock/Shareholder; Lilly. D.Dahl: Research Support; Lilly, Novo Nordisk, Eli Lilly and Company, Boehringer Ingelheim Inc., Amgen Inc. J.P.Frias: Advisory Panel; Becton, Dickinson and Company, Pfizer Inc., Sanofi, Consultant; Akero Therapeutics, Inc., 89bio, Inc., Aimmune, Boehringer Ingelheim Inc., Eli Lilly and Company, Carmot Therapeutics, Inc., Echosens, Merck & Co., Inc., Metacrine, Inc., Novo Nordisk, Pfizer Inc., Sanofi, Employee; Ionis Pharmaceuticals, Research Support; Akero Therapeutics, Inc., 89bio, Inc., Altimmune, Axcella Health Inc., Boehringer Ingelheim Inc., Eli Lilly and Company, Intercept Pharmaceuticals, Inc., Carmot Therapeutics, Inc., Janssen Pharmaceuticals, Inc., Madrigal Pharmaceuticals, Inc., Merck & Co., Inc., Metacrine, Inc., Novo Nordisk, Oramed Pharmaceuticals, Novartis, Pfizer Inc., Sanofi, Speaker's Bureau; Eli Lilly and Company, Sanofi. Funding Eli Lilly and Company