GLP-1 Drug Interactions: What the Labels Actually Say

Where GLP-1 interactions come from

Most drug interactions happen in the liver, when one drug speeds up or slows down the enzymes that clear another. GLP-1 medicines are peptides broken down like proteins, and in laboratory studies semaglutide showed very low potential to inhibit or induce those enzymes or to block drug transporters.¹ Their interactions come from two things they are meant to do: they slow the emptying of the stomach, which can change how quickly swallowed medicines are absorbed, and they lower blood sugar, which adds to other glucose-lowering drugs.

This article covers semaglutide (Ozempic, Wegovy) and tirzepatide (Mounjaro, Zepbound), whose labels are the most detailed. It describes what the labels and the studies behind them say; it cannot tell you what to do with your own medicines, which is a conversation for a prescriber or pharmacist who has your full list.

Slower stomach emptying and oral medicines

Every one of these labels says the drug delays gastric emptying and may affect the absorption of oral medicines taken with it.^1,2,3,4 What that means in practice has been measured for semaglutide injections. At steady state on 1 mg weekly, semaglutide was tested with metformin, an oral contraceptive (ethinylestradiol and levonorgestrel), warfarin, digoxin and atorvastatin, and none of their exposures changed to a clinically relevant degree, so no dose adjustment is required; a separate study found no apparent effect on the rate of gastric emptying at 2.4 mg.¹

The labels still ask for care with medicines where small changes matter. Wegovy's advises considering more clinical or laboratory monitoring for oral medicines with a narrow therapeutic index or that need monitoring anyway, and the tirzepatide labels say to monitor people on oral medicines that depend on threshold concentrations, naming warfarin as an example.^2,3

Insulin, sulfonylureas and low blood sugar

GLP-1 medicines release insulin only when blood sugar is raised, so on their own they rarely cause low blood sugar. Insulin and sulfonylureas lower it regardless, and the combination raises the risk of hypoglycaemia, including severe episodes. Each label advises considering a lower dose of the insulin or sulfonylurea when the GLP-1 medicine is started.^1,3 In SURPASS-2, where everyone took metformin but not insulin or sulfonylureas, blood sugar below 54 mg/dL was reported in 0.2 to 1.7% of people on tirzepatide and 0.4% on semaglutide.⁵

Oral contraceptives and tirzepatide

This is the interaction with the sharpest numbers. When a combined oral contraceptive (ethinyl estradiol with norgestimate) was taken after a single 5 mg dose of tirzepatide, peak levels of ethinyl estradiol, norgestimate and norelgestromin fell by 59%, 66% and 55%, total exposure fell by 20 to 23%, and peaks arrived 2.5 to 4.5 hours later.³ The Mounjaro and Zepbound labels therefore advise people using oral hormonal contraceptives to switch to a non-oral method, or add a barrier method, for 4 weeks after starting and for 4 weeks after each dose increase.^3,4

Semaglutide injections did not change oral contraceptive exposure in the label's study, and the semaglutide labels carry no such advice.¹ Vomiting and diarrhoea, common in the first weeks of either drug, can reduce the absorption of any pill, which is worth raising with a prescriber.

Levothyroxine and semaglutide tablets

Semaglutide tablets are taken on an empty stomach with an absorption enhancer, the same conditions under which levothyroxine is taken. In a study of 45 healthy adults, taking levothyroxine with semaglutide 14 mg tablets raised total thyroxine exposure by 33%, and the authors advised monitoring thyroid levels in people taking both.⁶ Wegovy's label reports the same 33% rise for the semaglutide tablet and advises monitoring.² No label reports this with the weekly injections.

Warfarin and other narrow-margin drugs

Semaglutide injections did not change warfarin exposure in the label's study.¹ The tirzepatide labels nonetheless name warfarin as a drug to monitor, because slowed stomach emptying could shift absorption and small changes in warfarin exposure matter.³ The practical reading is the same for any medicine whose dose is set by blood tests: tell whoever manages it when a GLP-1 medicine starts or its dose changes.

Surgery, sedation and aspiration

Because food can stay in the stomach longer, stomach contents can be inhaled during general anaesthesia or deep sedation. Every GLP-1 label now warns that pulmonary aspiration has been reported in people taking these drugs during elective procedures, and tells patients to inform their healthcare providers of any planned surgery or procedure.^2,4 In 2024 anaesthesia, surgery and gastroenterology societies published joint guidance on managing GLP-1 medicines around procedures.⁷ Whether to pause a dose, and for how long, is the procedure team's decision; the part that falls to the patient is telling them.

Medicines no label lists

Plenty of medicines are commonly asked about for which the labels list no interaction: statins, blood-pressure drugs, antidepressants, pain relievers. That is not the same as proof of no effect, but it means any advice about them is inference, not label guidance. Two indirect effects are real. Losing weight improved cardiometabolic measures in the pivotal trials, so doses of blood-pressure or diabetes medicines may need revisiting as weight falls.^8,9 And the labels warn that dehydration from vomiting or diarrhoea can injure the kidneys, which matters for anyone also taking drugs that affect kidney function.^2,4

Mental health warnings have changed. The Wegovy and Zepbound labels carried a warning about suicidal behaviour and ideation; both removed it in February 2026.^2,4

Two GLP-1 medicines, and research peptides

Combining two GLP-1 receptor agonists is advised against in both directions: Wegovy's label says so for semaglutide with any other GLP-1 receptor agonist, and Zepbound's for tirzepatide.^2,4 Compounded and grey-market products carry no label and were never tested for interactions, and research peptides taken alongside a GLP-1 medicine have no interaction data at all; our interaction checker shows which of its ratings rest on a label and which on mechanism alone.

Contraindications and pregnancy

All four labels carry a boxed warning about thyroid C-cell tumours seen in rodents and are contraindicated in people with a personal or family history of medullary thyroid carcinoma or with multiple endocrine neoplasia type 2.^2,4 For pregnancy, Wegovy's label says to stop when pregnancy is recognised when it is used for weight or cardiovascular risk, and Ozempic's says to stop at least two months before a planned pregnancy because of semaglutide's long washout.^2,1

Frequently asked questions

Does semaglutide or tirzepatide affect birth control pills?

Tirzepatide does: after a single dose, peak hormone levels fell by more than half, so its labels advise a non-oral or added barrier method for 4 weeks after starting and after each dose increase. Semaglutide injections did not change contraceptive levels in the label's study.

Can I take a GLP-1 medicine with insulin?

The labels allow it but warn that the combination raises the risk of low blood sugar and advise considering a lower insulin or sulfonylurea dose when starting.

Does semaglutide interact with levothyroxine?

The tablets do: levothyroxine exposure rose 33% when taken with semaglutide tablets, and the label advises monitoring. No label reports this with the weekly injections.

Do I need to stop my GLP-1 medicine before surgery?

Every label warns about aspiration during anaesthesia or deep sedation and tells patients to inform their providers of any planned procedure. Whether and when to pause is the procedure team's decision.

Is it safe to take statins or blood-pressure drugs with a GLP-1 medicine?

No label lists an interaction with them. Weight loss can lower blood pressure and blood sugar, so doses may need revisiting as weight falls.

Related on Grey Peptides

• Semaglutide vs tirzepatide
• Interaction checker
• GLP-1 titration planner
• Semaglutide encyclopedia entry
• Tirzepatide encyclopedia entry
• GLP-1 transition hub

Sources

1. Novo Nordisk. OZEMPIC (semaglutide) injection, US prescribing information: sections 7.1-7.2 and 12.3 (in vitro CYP and transporter potential; metformin, ethinylestradiol/levonorgestrel, warfarin, digoxin and atorvastatin studied at 1 mg; no dose adjustment); section 8 (discontinue at least 2 months before a planned pregnancy). DailyMed version of June 10, 2026, read September 30, 2026.
2. Novo Nordisk. WEGOVY (semaglutide) injection and tablets, US prescribing information: section 7 (levothyroxine exposure increased 33% with the semaglutide tablet; monitoring for narrow-therapeutic-index drugs); section 5 (pulmonary aspiration; acute kidney injury; boxed warning); section 8 (pregnancy); Suicidal Behavior and Ideation removed 02/2026. DailyMed version of June 30, 2026, read September 30, 2026.
3. Eli Lilly and Company. MOUNJARO (tirzepatide) injection, US prescribing information: sections 7.1-7.2 and 12.3 (ethinyl estradiol, norgestimate and norelgestromin Cmax reduced 59%, 66% and 55%, AUC 20-23%, after a single 5 mg dose; monitor narrow-therapeutic-index drugs such as warfarin; oral contraceptive advice). DailyMed version of September 2, 2026, read September 30, 2026.
4. Eli Lilly and Company. ZEPBOUND (tirzepatide) injection, US prescribing information: sections 5 and 7 (pulmonary aspiration; acute kidney injury due to volume depletion; oral contraceptive advice; coadministration with GLP-1 receptor agonists not recommended; boxed warning); Suicidal Behavior and Ideation removed 02/2026. DailyMed version of September 2, 2026, read September 30, 2026.
5. Frías, J. P. et al. (2021). Tirzepatide versus Semaglutide Once Weekly in Patients with Type 2 Diabetes. New England Journal of Medicine, 385(6), 503-515. PMID: 34170647 · doi:10.1056/NEJMoa2107519
6. Hauge, C. et al. (2021). Effect of oral semaglutide on the pharmacokinetics of thyroxine after dosing of levothyroxine and the influence of co-administered tablets on the pharmacokinetics of oral semaglutide in healthy subjects: an open-label, one-sequence crossover, single-center, multiple-dose, two-part trial. Expert Opinion on Drug Metabolism and Toxicology, 17(9), 1139-1148. PMID: 34289755 · doi:10.1080/17425255.2021.1955856
7. Kindel, T. L. et al. (2024). Multisociety clinical practice guidance for the safe use of glucagon-like peptide-1 receptor agonists in the perioperative period. Surgery for Obesity and Related Diseases, 20(12), 1183-1186. PMID: 39482213 · doi:10.1016/j.soard.2024.08.033
8. Wilding, J. P. H. et al. (2021). Once-Weekly Semaglutide in Adults with Overweight or Obesity. New England Journal of Medicine, 384(11), 989-1002. PMID: 33567185 · doi:10.1056/NEJMoa2032183
9. Jastreboff, A. M. et al. (2022). Tirzepatide Once Weekly for the Treatment of Obesity. New England Journal of Medicine, 387(3), 205-216. PMID: 35658024 · doi:10.1056/NEJMoa2206038

This article summarises US labels and published studies. It is not medical advice. Do not start, stop or change any medicine because of it; bring your full medicine list to a prescriber or pharmacist.