GLP1 agonists and oral contraception

Christie comes in to see you for a review of her oral contraceptive. She looks different…Currently on the progesterone-only pill, as she’s never been keen on LARCs and her weight precluded the COCP, she asks if she can now go on the combined pill as she’s finding the breakthrough bleeding on the POP really annoying. The penny drops. She’s clearly lost weight, and a quick check on the scales confirms her BMI has dropped from 33 to 27. She’s got no other risk factors, her blood pressure is good, so you talk through the COCP. She’s on her way out the door when she asks, ‘will it be OK with the other medication I’m on?’. 

Christie is one of an increasing number of our patients who has been buying Mounjaro through an online private pharmacy and whilst we hope the private providers will do thorough drug reviews and risk assessments, that may not always be the case. Concomitant use of an oral contraceptive with GLP1 agonist drugs (whether used for weight loss or type 2 diabetes) is going to be an increasingly common scenario and one we need to be mindful of. 

So what do we need to know about the GLP1 agonists (GLP1a) and oral contraceptives? 

Thankfully, the FSRH have recently produced guidance on this subject. As we know, the GLP1a drugs bind to and activate the GLP1 receptor, causing a range of effects, including increased insulin secretion, glucagon suppression and slowed gastric emptying. Tirzepatide (Mounjaro) is a dual-action drug that not only acts on the GLP1a receptor but also the glucose-dependent insulinotropic polypeptide (GIP) receptor, giving (potentially) more potent effects. Given the direct GI effects of these drugs, together with the potential GI side effects of vomiting and diarrhoea, all of which could affect oral contraceptive absorption, the FSRH guidance is both welcome and reassuring.

Unsurprisingly, the FSRH advise all women to use contraception whilst on GLP1a/GIP drugs - we have very limited data on the safety (or not) of these drugs in pregnancy, as reviewed by the UK teratology service (UKTIS). All evidence for the effects of GLP1a/GIP drugs on oral contraceptives comes from pharmacokinetic studies. 

Reassuringly, there is no evidence that the GLP1a drugs (semaglutide, dulaglutide, exenatide, lixisenatide or liraglutide) affect the bioavailability of oral contraceptives, so no additional barrier contraception is needed whilst on these drugs. However, tirzepatide does cause a clinically significant interaction, so whilst on tirzepatide the FSRH recommend alternative (non-oral) methods of contraception, or to add barrier methods for 4 weeks after initiation and after every dose increase. There is no evidence regarding the effects on emergency contraception, so the copper IUD is (ideally) recommended, or if levonorgestrel is used, a double dose is recommended if BMI >26 or weight >70kg.

What about diarrhoea and vomiting? If vomiting occurs within 3 hours of taking an oral contraceptive or if severe diarrhoea persists for >24 hours, condoms are recommended, and missed pill rules should be followed. If these side effects persist, non-oral contraception is recommended. 

What about preconception advice? A ‘washout’ period is recommended prior to any planned pregnancy, which varies depending on the drug pharmacokinetics - one month for tirzepatide, 2 months for semaglutide and 12 weeks for exenatide. 

So for Christie, we advise her to use additional barrier contraception for 4 weeks after any new dose increases of her Mounjaro, flag the recommendations if she were to develop diarrhoea or vomiting, and direct her to the helpful PIL put together by the FSRH, which summarises all the key information.