Disclosure: Clare J. Spencer, DM, has disclosed the following relevant financial relationships:
Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for: My Menopause Centre
Serve(d) as a speaker or a member of a speakers bureau for: National Health Service; My Menopause Centre (and has given talks to multiple other companies through My Menopause Centre)
Obesity is a complex public health issue associated with significant morbidity and mortality. According to the World Obesity Federation, more women than men were living with obesity in 2022. They are also more likely to use injectable medications for weight loss.
Importantly, women taking injectable weight loss drugs should use an effective form of contraception as a protective measure against their potential risks on foetal development. This makes it imperative for doctors to be aware of how injectable weight loss drugs affect the absorption of oral contraceptives. And, although no data currently exists, consideration should also be given to a potential impact on the absorption of oral hormone replacement therapy.
Glucagon-like peptide-1 (GLP-1) agonists were found to be effective for the management of type 2 diabetes and subsequently for weight loss. They bind to the GLP-1 receptor, resulting in an increase of insulin secretion, a decrease in glucagon secretion, and slower gastric emptying. Their impact on gastric emptying is greatest immediately following injection and when the dose is adjusted. This is also when they can influence the rate of absorption of oral medications that are taken concomitantly.
Commonly used weight loss injections include tirzepatide, semaglutide, liraglutide, exenatide, dulaglutide, and lixisenatide. In the UK, semaglutide is available through National Health Service (NHS) specialist weight loss services and tirzepatide was approved by the National Institute for Health and Care Excellence for managing overweight and obesity in December 2024.
Tirzepatide differs from other GLP-1 agonists in that it acts as a dual agonist, activating both the GLP-1 receptor and the glucose-dependent insulinotropic polypeptide receptor. This potentially leads to a greater impact on appetite suppression. Tirzepatide has been shown to be more effective for weight loss than semaglutide when both were given with diet and weight loss support.
Mounjaro ( tirzepatide) manufacturer Eli Lilly used paracetamol as a model drug to investigate the impact of delayed gastric emptying on oral medication absorption. Based on the results of that study, tirzepatide's summary of product characteristics says dose adjustments for most concomitantly administered oral medicines are not expected to be required. However, the manufacturer does recommend monitoring patients taking oral medications with a narrow therapeutic window, like warfarin and digoxin. The impact of a delayed effect should also be considered for other medications, such as where a rapid onset of effect is important.
When it comes to oral contraceptives, tirzepatide is the only weight loss injection that has been shown to have a clinically significant effect on the bioavailability of oral contraceptives in women. According to Eli Lilly, a clinical trial found that exposure to oral contraceptives was reduced after a single dose of tirzepatide, with the impact diminishing after subsequent doses.
It is important that clinicians and women are aware of this and that it is discussed at the time of prescribing and administration, especially since animal studies have demonstrated that GLP-1 agonists pose a risk of abnormalities to the developing foetus. No data for human pregnancy is currently available.
The British National Formulary advises that GLP-1 agonists should be avoided during pregnancy. It and the UK's Faculty of Sexual and Reproductive Healthcare also state that women of childbearing age should take effective contraception whilst using GLP-1 agonists.
Eli Lilly advises that women using oral contraception who plan to take tirzepatide should switch to a non-oral contraceptive method -- such as intrauterine, transdermal, vaginal, or injection -- or add in barrier methods of contraception for 4 weeks after initiation of tirzepatide and for 4 weeks after each dose increase, since the impact of tirzepatide on gastric emptying diminishes with time.
Furthermore, diarrhoea and vomiting are common side effects of all GLP-1 agonists and can also decrease contraception efficacy. Missed pill rules should be followed in these cases according to manufacturer instructions.
If GLP-1 injections can impact the availability of oral contraception, how about hormone replacement therapy (HRT)? There are currently no studies to inform us of this, but the delay in gastric emptying and the resulting decreasing hormone bioavailability could be a potential issue for women taking oral HRT and for those taking oral micronized progesterone for endometrial protection.
There is no doubt that GLP-1 agonists play an important role in obesity management. Women taking oral contraception need to be aware of the potential for loss of efficacy, and it would seem sensible to talk through the potential short-term impact on oral HRT while we wait for more data and clinical experience.