Oral Contraceptive Failure With GLP-1 and Dual GLP-1/GIP Therapies: A Case Report and Systematic Review of Incretin–COC Interactions [ID 3414]

INTRODUCTION: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and glucose-dependent insulinotropic polypeptide (GIP)/GLP-1 agonists delay gastric emptying and may alter combined oral contraceptive (COC) pharmacokinetics (PK). We report the first documented COC failure on semaglutide and systematically review agent-specific evidence to guide counseling. METHODS: Following PRISMA guidelines, PubMed, EMBASE, Web of Science, and ClinicalTrials.gov were searched for trials, PK studies, and observational reports evaluating incretin–COC interactions (area under the curve [AUC], maximum concentration [Cmax], time to maximum concentration [Tmax]) and contraceptive outcomes. U.S. Food and Drug Administration (FDA) reviews and package inserts were included. We also report the unintended pregnancy of a 39-year-old G4P2012 with obesity, conceived after 4 months of weekly semaglutide despite monophasic ethinyl estradiol/levonorgestrel COC use. RESULTS: Of 372 records, 10 studies (305 participants; 7 randomized crossover trials, 3 FDA reviews) met criteria. Most enrolled healthy, premenopausal participants, 4 evaluated postmenopausal women. Ethinyl estradiol exposure was unchanged across studies. Progestin effects varied: semaglutide/dulaglutide showed minimal levonorgestrel (LNG) AUC change (−8% to +5%), while tirzepatide, lixisenatide, and immediate pre-COC exenatide reduced LNG Cmax by 45–66% and AUC by 18–23%. Pooled analysis demonstrated consistent Tmax delays (mean difference 1.16 hours, 95% CI, 0.10–2.22). Short-acting agents consistently produced the largest PK changes when administered before COC use. Theoretic model of delayed gastric emptying also predicts greater persistence of Tmax delays in tirzepatide despite tachyphylaxis. CONCLUSIONS/IMPLICATIONS: GLP-1 and dual GLP-1/GIP agonists generally preserve estrogen exposure but can delay and reduce progestin bioavailability. While these changes are unlikely to compromise COC efficacy in typical use, counseling should address timing strategies, backup contraception during high-risk periods, and caution with progestin-only and emergency methods.