750-P: “SURPASS(ing)” an Era of Basal-Bolus Insulin Therapy—Tirzepatide vs. Insulin Lispro TID Added-on to Poorly Controlled Basal Insulin-Treated in Type 2 Diabetes

Abstract

Tirzepatide (TZP) is a once weekly GIP and GLP-1 receptor agonist for the treatment of type 2 diabetes (T2D). In this 52-wk open-label, multicenter, Phase 3b study, 1428 patients with T2D (mean baseline [BL] age 59 y; T2D duration 14 y; HbA1c 8.8%; BMI 33 kg/m2; insulin glargine (iGlar) dose 46 IU/day) were randomized (1:1:1:3) to TZP (5, 10, 15 mg) or insulin lispro (iLispro) TID, as an add-on to iGlar ± metformin. Insulin doses were titrated to a target fasting and pre-prandial glucose of 100-125 mg/dL. Primary efficacy measure was change in HbA1c from BL for TZP (pooled) vs iLispro at 52 wk. Secondary measures were change from BL in fasting serum glucose and body weight (BW), and proportion of patients at HbA1c and BW loss goals (TZP pooled and each dose vs iLispro). At 52 wk, TZP (pooled) was superior vs iLispro in change from BL in HbA1c, achieving a mean HbA1c of 6.5% vs 7.6%, with substantially less insulin use (iGlar: 13 IU/day vs 42 IU/day [iLispro 62 IU/day]) and BW loss of 10 kg vs gain of 4 kg, respectively. Rate of Level 2 and 3 hypoglycemia was 10-fold higher with iLispro (Table). The most common adverse events with TZP were nausea, diarrhea, and vomiting of mild to moderate severity. In conclusion, TZP demonstrated clinically meaningful and superior glycemic and BW control vs iLispro associated with substantially less hypoglycemia and insulin use. Disclosure J.Rosenstock: Advisory Panel; Applied Therapeutics Inc., Boehringer Ingelheim Inc., Eli Lilly and Company, Novo Nordisk, Oramed Pharmaceuticals, Sanofi, Zealand Pharma A/S, Intarcia Therapeutics, Inc., Hanmi Pharm. Co., Ltd., Research Support; Applied Therapeutics Inc., Boehringer Ingelheim Inc., Eli Lilly and Company, Merck & Co., Inc., Novartis, Novo Nordisk, Pfizer Inc., Sanofi, Intarcia Therapeutics, 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. H.W.Rodbard: Advisory Panel; Merck Sharp & Dohme Corp., Pacira BioSciences, Inc., Research Support; Eli Lilly and Company, Medtronic, Sanofi, Novo Nordisk. S.Tofe: Advisory Panel; Lilly, Novo Nordisk, Research Support; Lilly, Novo Nordisk, Speaker's Bureau; Lilly, Novo Nordisk. E.J.Sears: Employee; Eli Lilly and Company, Stock/Shareholder; Eli Lilly and Company. R.Huh: Employee; Eli Lilly and Company, Stock/Shareholder; Eli Lilly and Company. L.Fernandez lando: Employee; Eli Lilly and Company, Stock/Shareholder; Eli Lilly and Company. H.Patel: Employee; Eli Lilly and Company, Stock/Shareholder; Eli Lilly and Company. Funding Eli Lilly and Company