GLP-1 Drug Interaction Checker

Clinical effect

Co-administration of two GLP-1 receptor agonists is not recommended per the FDA Wegovy and Zepbound labels Section 7. No studies have evaluated combined use, and the additive risks (GI side effects, hypoglycemia in T2D, pancreatitis) make combination therapy clinically unjustified.

What to do

Do not use two GLP-1 receptor agonists at the same time. Switch by stopping the first drug and starting the second at its lowest dose on the next scheduled injection day (the standard practical-clinical switching guidance). Note: this is the practical clinical-practice guidance based on next-dose-day switching. Full pharmacokinetic washout (5 half-lives, ~35 days for semaglutide, ~25 days for tirzepatide) is what our washout calculator at /tools/glp1-washout-calculator uses for surgery/pregnancy planning. The two different guidances apply to different clinical contexts.

Clinical effect

Concomitant use of insulin with a GLP-1 receptor agonist increases the risk of hypoglycemia (low blood sugar), particularly during dose escalation.

What to do

Patients on insulin should have their insulin dose reduced when starting a GLP-1 receptor agonist, typically by 20% as a starting point. Blood glucose should be monitored closely. Discuss the dose-reduction plan with your prescriber BEFORE the first GLP-1 injection.

Clinical effect

Combining a sulfonylurea with a GLP-1 receptor agonist substantially increases the risk of hypoglycemia.

What to do

If you are on a sulfonylurea (glipizide, glyburide, glimepiride), your prescriber should typically reduce the sulfonylurea dose when starting a GLP-1 receptor agonist. Some patients are tapered off the sulfonylurea entirely. Monitor blood glucose closely.

Clinical effect

This interaction applies to FOUNDAYO (orforglipron) only — the injectable GLP-1s are peptides and are not affected. Foundayo is metabolized by CYP3A4, so strong CYP3A4 inhibitors raise Foundayo levels and strong CYP3A4 inducers can drop Foundayo levels enough to reduce its effectiveness.

What to do

If you take FOUNDAYO with a strong CYP3A4 inhibitor (e.g., ketoconazole, itraconazole, clarithromycin, ritonavir, cobicistat), do not exceed a Foundayo dose of 9 mg once daily. AVOID using Foundayo with a strong CYP3A4 inducer (e.g., rifampin, carbamazepine, phenytoin, St. John's Wort). With a moderate CYP3A4 inducer, your prescriber should monitor Foundayo effectiveness and escalate the dose as needed. This does not apply to Wegovy, Ozempic, Mounjaro, or Zepbound.

Clinical effect

Slowed gastric emptying may alter the absorption rate of warfarin and could affect INR. The clinical effect is usually small but variable.

What to do

Patients on warfarin should have their INR monitored more frequently when starting or escalating a GLP-1 receptor agonist. Dose adjustment is rarely needed but should be discussed with the prescriber managing your anticoagulation.

Clinical effect

The tirzepatide labels (Mounjaro and Zepbound) carry an explicit FDA directive for oral hormonal contraceptives because tirzepatide's pharmacokinetic study showed reduced contraceptive exposure after the first dose. Foundayo (oral orforglipron) carries the same type of directive. Semaglutide is different: the Wegovy and Ozempic labels report NO clinically significant change in ethinyl estradiol or levonorgestrel pharmacokinetics, so semaglutide does not require backup contraception.

What to do

If you take oral birth control and start TIRZEPATIDE (Mounjaro or Zepbound) or FOUNDAYO, the FDA label directs you to switch to a non-oral method (IUD, implant, injection, patch, ring) OR add a barrier method. Tirzepatide: for 4 weeks after starting and 4 weeks after each dose increase. Foundayo: for 30 days after starting and 30 days after each dose increase. Semaglutide (Wegovy/Ozempic) does not carry this requirement, but always confirm your contraception plan with your prescriber.

Clinical effect

Slowed gastric emptying may delay levothyroxine absorption. Total bioavailability is usually preserved but timing of TSH normalization may be affected.

What to do

Continue your normal levothyroxine routine (taken on an empty stomach 30-60 minutes before food and other medications). Monitor TSH levels at the standard 6-8 week interval after starting or escalating a GLP-1. Dose adjustment is rarely needed.

Clinical effect

Both opioids and GLP-1 receptor agonists slow gut motility. Combined use additively raises the risk of ileus, severe constipation, and fecal impaction — events listed in Section 6.2 (Postmarketing Experience) of every FDA-approved GLP-1 label.

What to do

Use the lowest effective opioid dose. Increase fluid and fiber. Stop the GLP-1 and seek emergency care immediately for any of: abdominal distension, no stool or gas for >24 hours, persistent vomiting, severe constant abdominal pain.

Clinical effect

Benzodiazepines distribute into adipose tissue. As body weight decreases on a GLP-1, the volume of distribution can shift, potentially raising effective plasma concentration at the same dose. Lorazepam volume of distribution decreased ~1.7-fold in one published weight-loss cohort.

What to do

Monitor for increased sedation, balance impairment, and morning grogginess — especially during the rapid-weight-loss phase (months 1-6). Discuss possible dose reduction with your prescriber if symptoms emerge. Do not adjust dose on your own.

Clinical effect

Slowed gastric emptying may delay the onset of action of acetaminophen by 30-60 minutes. Total exposure (AUC) is essentially preserved.

What to do

No specific action needed. Acetaminophen will still work but may take slightly longer to relieve pain or fever. Take as you normally would.

Clinical effect

Generally well tolerated together. Both drugs share GI side effects (nausea, diarrhea), which may be additive in the first weeks of GLP-1 therapy.

What to do

Continue metformin as prescribed. Be aware that nausea and diarrhea may temporarily be worse during the GLP-1 dose ramp. No dose adjustment of either drug is typically needed.

Clinical effect

For the injectable GLP-1s (semaglutide, tirzepatide) there is no clinically significant interaction — slowed gastric emptying may slightly delay statin absorption but total exposure and clinical effect are preserved (the Wegovy/Ozempic label reports no clinically significant change in rosuvastatin PK). FOUNDAYO (orforglipron) is the exception: because Foundayo raises simvastatin exposure, the label caps the simvastatin dose.

What to do

If you take an injectable GLP-1, continue statin therapy as prescribed — no timing changes needed. If you take FOUNDAYO, do not exceed simvastatin 20 mg once daily; other statins are not restricted. Confirm your statin dose with your prescriber when starting Foundayo.

Clinical effect

No specific interaction. GLP-1-induced weight loss may modestly lower blood pressure, which can be additive with antihypertensive therapy.

What to do

Continue blood pressure medications as prescribed. Monitor for symptomatic low blood pressure (lightheadedness on standing) as you lose weight, since you may need a dose reduction over time.

Clinical effect

No specific drug interaction. The 2024 EMA and FDA reviews of GLP-1 receptor agonists found no causal association with depression or suicidal ideation in randomized trials.

What to do

Continue antidepressant therapy as prescribed. If you have a history of depression, monitor mood actively in the first 8-12 weeks of GLP-1 therapy and discuss any changes with both your prescriber and mental health provider.

Clinical effect

No specific drug interaction. May actually be beneficial — GLP-1 receptor agonists can produce or worsen acid reflux, and PPIs/H2 blockers manage it.

What to do

Continue or initiate as needed for reflux symptoms. Discuss persistent or severe reflux with your prescriber.

Clinical effect

GLP-1-induced gastric emptying delay can mildly delay NSAID absorption (later Tmax, lower Cmax) but total daily exposure is generally preserved. Clinically usually not significant for episodic pain dosing.

What to do

Take as prescribed. Watch for unusual NSAID-related GI side effects, which can compound the GLP-1 GI burden during titration. If you need an NSAID for ongoing pain, discuss the timing and dose with your prescriber.

Clinical effect

GLP-1-induced gastric emptying delay can affect oral antibiotic absorption rates. Total exposure is generally preserved but onset of action may be delayed for some agents.

What to do

Take as prescribed and complete the full course. If severe nausea or vomiting on the GLP-1 prevents you from keeping antibiotic doses down, contact your prescriber promptly — antibiotic underdosing risks treatment failure and antimicrobial resistance.

Clinical effect

GLP-1 receptor agonists effectively counteract antipsychotic-induced weight gain in patients on long-term antipsychotic therapy. Multiple systematic reviews support this combination as beneficial; no clinically significant pharmacokinetic interaction has been documented.

What to do

Continue both medications under prescriber supervision. The GLP-1 can mitigate antipsychotic-driven weight gain without reducing antipsychotic efficacy. Coordinate with the prescribing psychiatrist or PCP.