In the phase 3 SURPASS studies of tirzepatide (TZP) , a novel dual GIP/GLP-1 receptor agonist developed for the treatment of type 2 diabetes, 23%-62% of TZP-treated participants achieved a HbA1c <5.7% and 54%-88% achieving ≥5% weight loss. This post hoc analysis evaluated the proportion of participants who achieved the triple endpoint of HbA1c <5.7%, ≥5% weight loss, and no clinically significant or severe hypoglycemia. We compared the proportion of participants achieving the triple endpoint between the TZP (5, 10, or 15 mg) and respective comparator groups using the efficacy analysis dataset without rescue medication. HbA1c and weight were evaluated at the end of the treatment period at week 40 (SURPASS 1, 2, 5) or week 52 (SURPASS 3, 4) . Hypoglycemia included blood glucose level <54 mg/dL with symptoms or severe hypoglycemia at any time. Significantly more participants treated with any dose of TZP achieved the triple endpoint compared to placebo or active comparators in SURPASS 1-5 (Figure) . Of the participants treated with TZP 15 mg, 45%, 48%, 48%, 41%, 55% reached the triple endpoint compared to 1% with placebo, 15% with semaglutide 1 mg, 2% with degludec, 1% with glargine U100, and 1% with placebo, in SURPASS 1-5, respectively. Significantly more participants treated with TZP achieved a HbA1c <5.7% with ≥5% weight loss and without hypoglycemia compared to placebo, semaglutide 1 mg, or basal insulin.


A.Y. Cheng: Advisory Panel; Abbott, AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Dexcom, Inc., Eli Lilly and Company, HLS Theraoeutics, Insulet Corporation, Janssen Pharmaceuticals, Inc., Medtronic, Novo Nordisk, Sanofi. Board Member; Type 1 Diabetes Think Tank Network. Speaker's Bureau; Bausch Health, Canada, Merck & Co., Inc. Other Relationship; Diabetes Canada. I. Lingvay: Advisory Panel; AstraZeneca, Boehringer Ingelheim International GmbH, Lilly, Mannkind, TARGET PharmaSolutions; Valeritas;; Altimmune; DataRevive; Click; Medscape Duke CRI; Janssen Pharma; Bayer; Intercept, Novo Nordisk, Sanofi, Zealand Pharma A/S. Consultant; Novo Nordisk. Research Support; NovoNordisk; Mylan; Merck, Sanofi. P. Choudhary: Advisory Panel; Abbott Diabetes, Lilly Diabetes, Medtronic. Research Support; Novo Nordisk. Speaker's Bureau; Dexcom, Inc., Glooko, Inc., Insulet Corporation, Sanofi. E. Gomez-Valderas: Employee; Lilly. Stock/Shareholder; Lilly. S. Allen: None. K.T. Ranta: Employee; Eli Lilly and Company. J.A. Levine: Employee; Eli Lilly and Company. Stock/Shareholder; Eli Lilly and Company. V. Thieu: None.


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