Clinical Factors Associated with Insulin Regression When Adding Tirzepatide in Basal Insulin–Treated Type 2 Diabetes

Given that basal insulin dose decreased over time, and up to 19% of tirzepatide (TZP)-treated participants discontinued basal insulin by Week 52 in SURPASS-6, what clinical parameters were associated with insulin regression (use<10 IU/day) at Week 52?

Methods: In SURPASS-6, TZP was added to basal insulin glargine in participants with inadequately controlled type 2 diabetes (T2D). 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.

 

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Interessenkonflikt

V. T. T., H. P., J. K., C. J. L. and H. W. are employees and shareholders of: Eli Lilly and Company. J. R., served on scientific advisory boards and received honorarium or consulting fees from: Applied Therapeutics, Boehringer Ingelheim, Eli Lilly and Company, Hanmi Pharmaceutical, Intarcia Therapeutics, Novo Nordisk, Oramed Pharmaceuticals, Sanofi, Structure Therapeutics, Terns Pharmaceuticals, and Zealand Pharma. Received grants and research support from: Applied Therapeutics, Boehringer Ingelheim, Eli Lilly and Company, GlaxoSmithKline, Hanmi Pharmaceutical, Intarcia Therapeutics, Lexicon Pharmaceuticals, Merck, Novo Nordisk, Oramed Pharmaceuticals, Pfizer, and Sanofi. S. T., served on scientific advisory boards, received research support, and received honorarium or consulting fees from: Eli Lilly and Company, GlaxoSmithKline, Novo Nordisk, and Sanofi. C. W., served on scientific advisory boards and/or received honorarium from: Abbott, Biomea Fusion, Eli Lilly and Company, and Novo Nordisk. Received research funding from: Bayer, Corcept Therapeutics, Eli Lilly and Company, Novo Nordisk, Regeneron, and Vanda Therapeutics.

Publication History

Article published online:
28 May 2025