J Am Pharm Assoc (2003). 2024 Jan-Feb;64(1):204-211.e4. doi: 10.1016/j.japh.2023.10.037. Epub 2023 Nov 7.
Tirzepatide is a dual glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptor agonist (RA) whose mechanism of action leads to a greater effect of gastric emptying (GE) than typical GLP-1 RAs. After the first dose of tirzepatide, GE is most substantially delayed. The drug then undergoes tachyphylaxis after subsequent doses. Although data on GLP1-RAs have historically demonstrated a lack of impact on bioavailability of oral hormonal contraceptives, manufacturer recommendations for tirzepatide indicate an interaction exists.
The objectives of this literature review were to review trial data on differences in the impact of tirzepatide and GLP-1 RAs on oral hormonal contraceptives and provide an analysis of safety data between oral contraceptives and incretin agents.
PubMed and Google Scholar were searched using the generic name for the GLP-1/GIP agent, the generic names for GLP-1 RAs and hormonal contraceptives, followed by the generic names plus the interacting medication. A total of 6 clinical trials were selected for inclusion in the literature review.
Of the 6 articles included in the review, one investigated the use of tirzepatide and showed a statistically significant reduction in area under the plasma drug concentration-time curve, maximum concentration, and time to maximum plasma concentration when tirzepatide was concomitantly administered with an oral hormonal contraceptive. The remaining 5 studies involving GLP-1 RAs did not show a statistically or clinically significant difference of impact of the agents on oral hormonal contraceptives.
It could be suggested that tirzepatide had a greater impact on absorption of oral hormonal contraceptives than other GLP-1 RAs. The rapid dose escalation and greater delay on GE enhanced the impact on oral medications such as contraceptives. This differed from other GLP-1 RAs and creates a unique need for enhanced provider and patient education regarding the management of this interaction and future studies to evaluate this interaction further.
替西帕肽是一种双重胰高血糖素样肽 1（GLP-1）和葡萄糖依赖性胰岛素促分泌多肽（GIP）受体激动剂（RA），其作用机制导致胃排空（GE）的效果大于典型的 GLP-1 RA。替西帕肽的首剂后，GE 被延迟。药物在随后的剂量中经历快速脱敏。虽然 GLP1-RA 的数据历史上表明对口服激素避孕药的生物利用度没有影响，但替西帕肽的制造商建议表明存在相互作用。
本文献综述的目的是回顾关于替西帕肽和 GLP-1 RA 对口服激素避孕药影响的试验数据，并分析口服避孕药和肠促胰岛素之间的安全性数据。
使用 GLP-1/GIP 制剂的通用名称、GLP-1 RA 和激素避孕药的通用名称，以及加用药物的通用名称，在 PubMed 和 Google Scholar 上进行搜索。共选择了 6 项临床试验纳入文献综述。
在纳入的综述的 6 篇文章中，有一篇研究了替西帕肽的使用，结果表明替西帕肽与口服激素避孕药同时给药时，血浆药物浓度-时间曲线下面积、最大浓度和达峰时间显著降低。其余 5 项涉及 GLP-1 RA 的研究未显示药物对口服激素避孕药的影响在统计学或临床上有显著差异。
可以认为替西帕肽对口服激素避孕药的吸收影响大于其他 GLP-1 RA。快速剂量递增和 GE 延迟增强了对避孕药等口服药物的影响。这与其他 GLP-1 RA 不同，因此需要加强提供者和患者对这种相互作用的管理和未来研究进一步评估这种相互作用的教育。
