Can a woman on oral contraceptive pills (OCP) take a Glucagon-like peptide-1 (GLP-1) receptor agonist (GLP-1 RA)?

Can a Woman on Oral Contraceptive Pills Take GLP-1 Receptor Agonists?

Yes, women on oral contraceptive pills can take GLP-1 receptor agonists, as GLP-1 RAs do not reduce the bioavailability of oral contraceptives and there are no contraindications to concurrent use. 1

Key Evidence on Drug Interaction

Pharmacokinetic studies demonstrate that GLP-1 RAs do not interfere with oral contraceptive effectiveness. A dedicated drug interaction study with semaglutide (a once-weekly GLP-1 RA) showed that it did not reduce the bioavailability of ethinylestradiol, and the area under the curve for ethinylestradiol met bioequivalence criteria (ratio 1.11, within the 0.80-1.25 range). 1 Levonorgestrel exposure was actually 20% higher during semaglutide treatment, which does not compromise contraceptive efficacy. 1

Critical Contraception Counseling Required

Despite the lack of drug interaction, all women of reproductive potential taking GLP-1 RAs must use reliable contraception to prevent unintended pregnancy. 2, 3 This is because:

• GLP-1 RAs are contraindicated in pregnancy due to insufficient safety data. 2
• Weight loss from GLP-1 RAs can restore fertility in women with obesity-related oligomenorrhea, leading to unplanned pregnancies. 3
• Current evidence on periconceptional GLP-1 RA exposure is limited to case reports and observational studies, with insufficient data to predict fetal outcomes. 3

Special Considerations After Bariatric Surgery

If the patient has undergone bariatric surgery (RYGB or sleeve gastrectomy), combined oral contraceptives containing estrogen should be avoided due to potential malabsorption and increased VTE risk. 2 In this specific scenario:

• Long-acting reversible contraception (LARC) methods such as implants, IUDs, or IUS should be first-line. 2
• Progestin-only pills may have reduced reliability after malabsorptive procedures. 2
• The GLP-1 RA can still be used, but contraceptive method selection requires adjustment. 2

Monitoring Considerations

Women with polycystic ovary syndrome (PCOS) on combined therapy with metformin, OCPs, and GLP-1 RAs may have increased risk of reactive hypoglycemia. One study showed the prevalence of reactive hypoglycemia increased from 13% to 22% during combined metformin and OCP treatment. 4 Monitor for hypoglycemic symptoms if using this triple combination, though this is primarily relevant in the PCOS population.

Hypertension Context

OCPs themselves are associated with modest blood pressure elevations, and this should be factored into the overall cardiovascular risk assessment when prescribing both medications. 2 However, this does not contraindicate concurrent use—it simply requires blood pressure monitoring as part of routine OCP management. 2

Bottom Line Algorithm

1. Confirm reliable contraception is in place before starting GLP-1 RA (OCPs are acceptable). 2, 3
2. If no bariatric surgery history: Continue OCPs as prescribed; no dose adjustment needed. 1
3. If post-bariatric surgery: Switch to LARC method before or concurrent with GLP-1 RA initiation. 2
4. Monitor blood pressure per standard OCP guidelines. 2
5. Counsel on pregnancy prevention and the need to discontinue GLP-1 RA at least 2 months before planned conception. 3