Introduction & Objective: In the SURPASS-6 trial, tirzepatide (TZP) added to basal insulin glargine U100 significantly improved HbA1c and body weight in participants with inadequately controlled type 2 diabetes (T2D). Overall, basal insulin dose decreased over time, and up to 19% of TZP-treated participants discontinued basal insulin by Week 52. We aimed to identify clinical parameters associated with insulin regression (use <10 IU/day) at Week 52.
Methods: Analyses included participants receiving TZP at Week 52 (≥75% adherence) without rescue medication. The outcome was basal insulin discontinuation or <10 IU/day use at Week 52 (“insulin regressor group”) or ≥10 IU/day use at Week 52 (“insulin non-regressor group”). Association between the outcome and baseline variables was assessed by univariate logistic regression. Variables with p<0.2 entered stepwise multivariate logistic regression.
Results: A total of 145 and 496 participants were included in the insulin regressor and insulin non-regressor groups, respectively. Overall, 34.2%, 33.9%, and 32.0% of participants were on TZP 5 mg, 10 mg, and 15 mg, respectively. At baseline, mean age was 58.2 years; 59.3% were female; median insulin daily use was 46 IU; and mean fasting serum glucose (FSG) was 158 mg/dL. In the multivariate analysis, baseline factors associated with insulin regression were (odds ratio [OR] [95% CI]): TZP 10 mg vs. 5 mg: 1.84 (1.08-3.13), p=0.024; TZP 15 mg vs. 5 mg: 3.78 (2.25-6.35) p<0.001; female vs. male: 1.74 (1.14-2.67), p=0.011; daily insulin dose (by 1 SD decrease: 1.76 [1.36-2.27], p<0.001); and FSG (by 1 SD decrease: 1.38 [1.08-1.75], p=0.01). Some of the baseline factors not associated with insulin discontinuation or reduction were duration of diabetes, HbA1c, triglycerides, and eGFR.
Conclusion: Several clinical factors were associated with basal insulin regression in SURPASS-6, including higher randomized TZP dose, lower insulin daily dose, and lower FSG at baseline.
C.H. Wysham: Research Support; Eli Lilly and Company. Speaker's Bureau; Eli Lilly and Company. Research Support; Novo Nordisk. Consultant; Novo Nordisk. Speaker's Bureau; Novo Nordisk. Advisory Panel; Abbott. Research Support; Bayer Inc. Advisory Panel; Biomea Fusion, Inc. Research Support; Corcept Therapeutics, AbbVie Inc. J. Rosenstock: Research Support; Biomea Fusion, Inc. Other Relationship; Lilly Diabetes. Research Support; Merck & Co., Inc., Novartis Pharmaceuticals Corporation, Corcept Therapeutics. Other Relationship; Novo Nordisk. Research Support; Pfizer Inc. Other Relationship; Sanofi, Boehringer-Ingelheim. Research Support; Shionogi & Co., Ltd. Other Relationship; Structure Therapeutics, Inc. Advisory Panel; Terns Pharmaceuticals, Zealand Pharma A/S. Other Relationship; Applied Therapeutics, Hanmi Pharm. Co., Ltd., Oramed Pharmaceuticals. Advisory Panel; Scholar Rock. S. Tofe: None. V. Thieu: Employee; Eli Lilly and Company. J.I. Kiljanski: Employee; Eli Lilly and Company. Stock/Shareholder; Eli Lilly and Company. C. Lee: Employee; Eli Lilly and Company. Stock/Shareholder; Eli Lilly and Company. H. Wang: None. H. Patel: None.
