GLP-1 Drug Interaction Checker

Clinical effect

Section 7 of the FDA labels for Wegovy and for Zepbound advises against running two GLP-1 receptor agonists together. Nobody has studied the combination, and what stacks up if you try it — pancreatitis, GI side effects, hypoglycemia where T2D is present — leaves no clinical case for it.

What to do

Never run the two together. To change drugs, stop the first and begin the second at its lowest dose on what would have been the next injection day — that is the ordinary switching guidance used in practice. It is not the same thing as a full pharmacokinetic washout, which runs 5 half-lives: roughly 25 days for tirzepatide, roughly 35 days for semaglutide. Our washout calculator at /tools/glp1-washout-calculator uses those figures, because planning around surgery or pregnancy is a different question from switching drugs.

Clinical effect

Insulin taken alongside a GLP-1 receptor agonist makes hypoglycemia — blood sugar falling too low — more likely, and the escalation weeks are when it is likeliest.

What to do

Anyone already on insulin needs that dose brought down as the GLP-1 starts — 20% is the usual opening reduction. Watch blood glucose closely from there. Agree that reduction with your prescriber BEFORE any GLP-1 is injected, not after.

Clinical effect

Put a sulfonylurea together with a GLP-1 receptor agonist and hypoglycemia becomes substantially more likely.

What to do

On a sulfonylurea — glimepiride, glyburide, glipizide — expect your prescriber to cut that dose as the GLP-1 begins. Some people come off the sulfonylurea altogether. Either way, keep a close watch on blood glucose.

Clinical effect

FOUNDAYO (orforglipron) alone is affected here; the injectable GLP-1s are peptides and sit outside it. Because CYP3A4 metabolizes Foundayo, a strong inhibitor of that enzyme pushes Foundayo levels up, and a strong inducer can pull them down far enough to cost you the effect.

What to do

Where FOUNDAYO meets a strong CYP3A4 inhibitor — cobicistat, ritonavir, clarithromycin, itraconazole, ketoconazole — hold the Foundayo dose at 9 mg once daily and go no higher. A strong CYP3A4 inducer is worse: AVOID the pairing outright, and that means rifampin, carbamazepine, phenytoin and St. John's Wort. Moderate inducers call for your prescriber to watch whether Foundayo is still working and raise the dose if it is not. None of this reaches Wegovy, Ozempic, Mounjaro or Zepbound.

Clinical effect

With the stomach emptying more slowly, warfarin may be absorbed at a different rate and INR may shift with it. In practice the effect is usually small, though it varies between people.

What to do

Step up INR monitoring whenever a GLP-1 receptor agonist is started or its dose raised. Changing the warfarin dose is rarely called for, but that call belongs to whoever manages your anticoagulation.

Clinical effect

Where oral hormonal contraceptives are concerned the drugs part company. Tirzepatide's pharmacokinetic study found contraceptive exposure dropping after the first dose, so the Mounjaro and Zepbound labels carry an explicit FDA directive, and Foundayo (oral orforglipron) carries one of the same kind. Semaglutide does not: the Ozempic and Wegovy labels report NO clinically significant change in levonorgestrel or ethinyl estradiol pharmacokinetics, and no backup contraception is required with it.

What to do

Starting TIRZEPATIDE (Mounjaro or Zepbound) or FOUNDAYO while on oral birth control means following the FDA label: either move to a non-oral method — ring, patch, injection, implant, IUD — or add a barrier method on top. How long depends on the drug. On Foundayo the cover runs 30 days from the start, then a further 30 days from each dose increase. On tirzepatide it is 4 weeks from the start, and 4 weeks again from each dose increase. No such requirement attaches to semaglutide (Wegovy/Ozempic), though your contraception plan is still worth confirming with your prescriber.

Clinical effect

Levothyroxine may be absorbed later than usual once gastric emptying slows. Total bioavailability generally holds up; what can shift is when TSH settles.

What to do

Keep the routine you already have — empty stomach, 30-60 minutes ahead of food and any other medication. After a GLP-1 starts or steps up, check TSH on the usual 6-8 week interval. It is rare for the dose to need changing.

Clinical effect

Gut motility slows under opioids and under GLP-1 receptor agonists alike, and using both compounds the risk of fecal impaction, severe constipation and ileus. Every FDA-approved GLP-1 label lists those events in Section 6.2, Postmarketing Experience.

What to do

Keep the opioid at the lowest dose that works, and push fluid and fiber up. Four things mean stopping the GLP-1 and getting emergency care straight away: severe constant abdominal pain, persistent vomiting, abdominal distension, or >24 hours with no stool or gas.

Clinical effect

Adipose tissue is where benzodiazepines distribute. Lose body weight on a GLP-1 and their volume of distribution can shift, which lets the same dose reach a higher effective plasma concentration. One published weight-loss cohort recorded lorazepam's volume of distribution falling ~1.7-fold.

What to do

Watch for morning grogginess, impaired balance and deeper sedation, most of all through the rapid-weight-loss phase in months 1-6. If any of that appears, raise a dose reduction with your prescriber — never make the change yourself.

Clinical effect

Acetaminophen may take 30-60 minutes longer to start working once gastric emptying slows. Total exposure, the AUC, is essentially unchanged.

What to do

Nothing to do differently. Take it as you always have; relief from pain or fever may simply arrive a little later.

Clinical effect

The pair is generally well tolerated. Both bring the same GI side effects — diarrhea, nausea — and in the opening weeks of GLP-1 therapy those can stack.

What to do

Stay on metformin as prescribed. Expect diarrhea and nausea to be temporarily worse while the GLP-1 dose is ramping. Neither drug usually needs its dose changed.

Clinical effect

Nothing clinically significant arises with the injectable GLP-1s, tirzepatide and semaglutide. Gastric emptying slows, which can put statin absorption slightly behind schedule, yet total exposure and clinical effect both survive that — rosuvastatin PK shows no clinically significant change in what the Wegovy/Ozempic label reports. FOUNDAYO (orforglipron) breaks the pattern: it raises simvastatin exposure, and the label caps the simvastatin dose accordingly.

What to do

On an injectable GLP-1, nothing changes: carry on with the statin as prescribed, at the same times. On FOUNDAYO, simvastatin stops at 20 mg once daily and must go no higher; no other statin is restricted. Confirm the dose with your prescriber as Foundayo starts.

Clinical effect

No interaction as such. The GLP-1-induced weight loss tends to bring blood pressure down a little on its own, and that adds to whatever the antihypertensive is already doing.

What to do

Keep taking your blood pressure medication as prescribed, but watch for the signs of it running too low — lightheadedness when you stand. As the weight comes off, the dose may need reducing.

Clinical effect

No drug interaction as such. Reviewing the randomized trials in 2024, neither the FDA nor the EMA could establish that GLP-1 receptor agonists cause suicidal ideation or depression.

What to do

Stay on the antidepressant as prescribed. Where there is a history of depression, keep active track of mood through the first 8-12 weeks on a GLP-1, and take anything that shifts to your mental health provider as well as your prescriber.

Clinical effect

No drug interaction as such, and the pairing may work in your favor: acid reflux is something a GLP-1 receptor agonist can bring on or aggravate, and managing it is exactly what PPIs/H2 blockers do.

What to do

Carry on with it, or start it, as reflux symptoms require. Take reflux that is severe or will not settle to your prescriber.

Clinical effect

NSAID absorption can run slightly late behind GLP-1-induced gastric emptying delay — Tmax later, Cmax lower — while total daily exposure generally survives intact. For pain dosed episodically this rarely matters clinically.

What to do

Take it as prescribed, and keep an eye out for NSAID-related GI effects that seem out of the ordinary — during titration they add to what the GLP-1 is already doing. Ongoing pain that needs an NSAID is worth a conversation with your prescriber about dose and timing.

Clinical effect

The rate at which an oral antibiotic is absorbed can change under GLP-1-induced gastric emptying delay. Total exposure generally holds; with some agents, onset simply arrives later.

What to do

Take it as prescribed and finish the course. Should vomiting or severe nausea on the GLP-1 stop you keeping doses down, tell your prescriber promptly: an underdosed antibiotic invites antimicrobial resistance and treatment failure.

Clinical effect

For anyone on long-term antipsychotic therapy, a GLP-1 receptor agonist works against the weight gain those drugs cause. Several systematic reviews back the combination, and no clinically significant pharmacokinetic interaction has been documented.

What to do

Stay on both, supervised by your prescriber. Antipsychotic efficacy is not reduced by the GLP-1, which meanwhile blunts the weight gain. Keep the prescribing psychiatrist or PCP in the loop.