Introduction & Objective: In the SURPASS-3 (S-3) and -4 (S-4) trials, tirzepatide (TZP) reduced HbA1c and body weight (BW) in participants with type 2 diabetes (T2D) vs. basal insulin (BI). We assessed the efficacy and safety of TZP and BI in those who did or did not achieve fasting serum glucose (FSG) targets.
Methods: Post hoc analysis of participants who achieved FSG <90 mg/dL (S-3) or <100 mg/dL (S-4) vs. those who did not at Week 52. Efficacy analyses included those on assigned treatment without rescue medication.
Results: In S-3 and S-4, respectively, 234 (18%) and 596 (33%) participants achieved FSG targets. Baseline (BL) demographics were similar between studies, but BL FSG was lower in those achieving FSG targets. Participants achieving FSG targets had a greater reduction in HbA1c and BW at Week 52 than those who did not; HbA1c reduction was greater with TZP compared with BI in those who did or did not achieve FSG target (Figure). The percentage reporting ≥1 adverse event (AE) was similar between studies. In S-3 and S-4, across TZP doses, clinically significant hypoglycemia aggregated rate/year was 0.018-0.197 in those who achieved FSG targets, and 0.009-0.099 in those who did not.
Conclusion: TZP reduced HbA1c and BW regardless of FSG target attainment, without substantial differences in AEs nor hypoglycemia. BI was associated with weight gain and less HbA1c reduction than TZP.
A.Y.Y. Cheng: Advisory Panel; Abbott. Speaker's Bureau; Amgen Inc., AstraZeneca, Bausch Health. Advisory Panel; Bayer Inc. Speaker's Bureau; Abbott, Bayer Inc. Research Support; Applied Therapeutics Inc. Advisory Panel; Boehringer-Ingelheim. Speaker's Bureau; Boehringer-Ingelheim, Dexcom, Inc. Advisory Panel; Dexcom, Inc., Eli Lilly and Company. Speaker's Bureau; Eli Lilly and Company. Advisory Panel; Eisai Inc. Speaker's Bureau; GlaxoSmithKline plc. Advisory Panel; HLS Therapeutics Inc. Speaker's Bureau; HLS Therapeutics Inc., Insulet Corporation. Advisory Panel; Insulet Corporation, Janssen Pharmaceuticals, Inc. Speaker's Bureau; Janssen Pharmaceuticals, Inc., Medtronic. Advisory Panel; Novo Nordisk. Speaker's Bureau; Novo Nordisk. Research Support; Novo Nordisk. Speaker's Bureau; Pfizer Inc. Advisory Panel; Sanofi. Speaker's Bureau; Sanofi. Research Support; Sanofi. Advisory Panel; Takeda Canada, AstraZeneca, Sanofi. Consultant; Abbott, AstraZeneca, Bayer Inc., Boehringer-Ingelheim, Dexcom, Inc., Eisai Inc., Eli Lilly and Company, Insulet Corporation, HLS Therapeutics Inc., Janssen Pharmaceuticals, Inc., Novo Nordisk, Sanofi, Takeda Pharmaceutical Company Limited. J.B. Green: Consultant; AstraZeneca, Novo Nordisk, Pfizer Inc., Bayer Inc., Anji Pharmaceuticals, Boehringer-Ingelheim, Valo Health, Eli Lilly and Company, Vertex Pharmaceuticals Incorporated. Research Support; Merck, Roche, Lilly, Boehringer Ingelheim, Bluedrop. J.M. Maldonado: None. M. Liu: Consultant; Eli Lilly and Company. R.B. Silva: None. A. Kwan: Employee; Eli Lilly and Company. Stock/Shareholder; Eli Lilly and Company.
