GLP-1 drug interactions

GLP-1 Drug Interaction Checker

Search any medication to see how it interacts with Wegovy, Ozempic, Zepbound, Mounjaro, or Foundayo. Every entry is severity-tiered and cites the specific FDA prescribing-information section it comes from. Currently 12 verified interactions in the database.

Filter by severity

Showing 12 of 12 entries. Every entry cites its FDA prescribing information section. This tool is educational and does NOT replace your prescriber or pharmacist.

Other GLP-1 receptor agonists

GLP-1 receptor agonist

Do not combine

Common brand names

Wegovy · Ozempic · Rybelsus · Zepbound · Mounjaro · Foundayo · Saxenda · Victoza · Trulicity · Bydureon · Byetta

Clinical effect

Combining two GLP-1 receptor agonists is not recommended. There is no added benefit and the risk of severe GI side effects, hypoglycemia, and pancreatitis is increased.

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, with the standard 1-week washout (next scheduled injection day).

Mechanism

Both drugs target the same GLP-1 receptor. Co-administration produces no additional efficacy but doubles the receptor activation, magnifying side effects.

Source: Wegovy PI Section 7.1; Zepbound PI Section 7.1; Foundayo PI

Insulin

Insulin (long, intermediate, or rapid acting)

Serious — close monitoring

Common brand names

Lantus · Toujeo · Basaglar · Tresiba · Levemir · Humalog · Novolog · Apidra · Fiasp · Lyumjev · Humulin · Novolin

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.

Mechanism

GLP-1 receptor agonists enhance glucose-dependent insulin secretion and reduce glucagon. Adding exogenous insulin on top of this effect creates additive hypoglycemic risk.

Source: Wegovy PI Section 7.2; Ozempic PI Section 7.1; Zepbound PI Section 7.2; Foundayo PI

Sulfonylureas

Sulfonylurea (oral diabetes medication)

Serious — close monitoring

Common brand names

Glucotrol · glipizide · DiaBeta · Glynase · Micronase · glyburide · Amaryl · glimepiride

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.

Mechanism

Sulfonylureas force insulin secretion regardless of glucose level. GLP-1 receptor agonists add a glucose-dependent insulin boost on top, producing additive hypoglycemia risk that is more pronounced than with insulin alone.

Source: Wegovy PI Section 7.2; Ozempic PI Section 7.1; Zepbound PI Section 7.2

Warfarin

Anticoagulant

Moderate — be aware

Common brand names

Coumadin · Jantoven

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.

Mechanism

GLP-1 receptor agonists slow gastric emptying. Warfarin absorption may be delayed but total bioavailability is generally preserved.

Source: Wegovy PI Section 7.3 (oral medications general)

Oral contraceptives (combined and progestin-only)

Oral contraceptive

Moderate — be aware

Common brand names

Yasmin · Yaz · Loestrin · Lo Loestrin Fe · Microgestin · Sprintec · Tri-Sprintec · Ortho Tri-Cyclen · Necon · Junel · Mononessa · Camila · Errin · Slynd

Clinical effect

Slowed gastric emptying may affect the absorption of oral contraceptives, particularly during dose escalation. Pharmacokinetic studies of injectable semaglutide and tirzepatide have NOT demonstrated reduced contraceptive bioavailability, but the FDA labels recommend caution. Foundayo (oral orforglipron) carries a more specific warning.

What to do

If you take oral birth control, talk to your prescriber about adding a backup contraception method (barrier, IUD, implant, or non-oral hormonal) for the first 16-20 weeks of GLP-1 therapy and during any dose increase. The Foundayo label specifically recommends backup contraception for 30 days after starting and 30 days after each dose increase.

Mechanism

Slowed gastric emptying may reduce or delay absorption of oral medications. Effect on oral contraceptives is theoretical for injectable GLP-1s and labeled for Foundayo.

Source: Foundayo PI (Section 7.1); Wegovy PI Section 7.3; Zepbound PI Section 7.3

Levothyroxine (thyroid hormone replacement)

Thyroid hormone

Moderate — be aware

Common brand names

Synthroid · Levoxyl · Tirosint · Unithroid

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.

Mechanism

Slowed gastric emptying delays absorption of orally administered levothyroxine. The 30-60 minute pre-breakfast window is usually sufficient to preserve absorption.

Source: Wegovy PI Section 7.3 (oral medications general)

Acetaminophen (paracetamol)

Analgesic / antipyretic

Minor — generally safe

Common brand names

Tylenol · Panadol · FeverAll

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.

Mechanism

GLP-1 receptor agonists slow gastric emptying by approximately 30-60 minutes at therapeutic doses. Acetaminophen absorption is delayed proportionally.

Source: Wegovy PI Section 7.3 — acetaminophen is the standard probe drug used to measure GLP-1 effect on gastric emptying in PK studies

Metformin

Biguanide (oral diabetes medication)

Minor — generally safe

Common brand names

Glucophage · Glumetza · Fortamet · Riomet

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.

Mechanism

Independent mechanisms (metformin: AMPK activation, decreased hepatic glucose production; GLP-1: enhanced glucose-dependent insulin secretion). Both produce GI side effects independently.

Source: Common combination, no specific FDA label warning

Statins (HMG-CoA reductase inhibitors)

Cholesterol medication

Minor — generally safe

Common brand names

Lipitor · atorvastatin · Crestor · rosuvastatin · Zocor · simvastatin · Pravachol · pravastatin · Mevacor · lovastatin

Clinical effect

No clinically significant interaction. Slowed gastric emptying may slightly delay statin absorption but the total exposure and clinical effect are preserved.

What to do

Continue statin therapy as prescribed. No timing changes needed.

Mechanism

Statins are not significantly affected by the slowed gastric emptying produced by GLP-1 receptor agonists.

Source: No specific FDA label warning

ACE inhibitors and ARBs (blood pressure medications)

Blood pressure medication

Minor — generally safe

Common brand names

Lisinopril · Zestril · Prinivil · losartan · Cozaar · valsartan · Diovan · irbesartan · Avapro · olmesartan · Benicar

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.

Mechanism

Weight loss reduces blood pressure independently. Combined with antihypertensive therapy this can occasionally produce hypotension.

Source: Common combination, no specific FDA label warning

SSRIs and SNRIs (antidepressants)

Antidepressant

Minor — generally safe

Common brand names

Lexapro · escitalopram · Zoloft · sertraline · Prozac · fluoxetine · Paxil · paroxetine · Cymbalta · duloxetine · Effexor · venlafaxine · Wellbutrin · bupropion

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.

Mechanism

Independent mechanisms with no documented pharmacokinetic interaction.

Source: EMA PRAC review April 2024; FDA evaluation 2024 — no signal of psychiatric harm in RCTs

PPIs and H2 blockers (acid reflux medications)

Acid suppression

Minor — generally safe

Common brand names

Prilosec · omeprazole · Nexium · esomeprazole · Protonix · pantoprazole · Pepcid · famotidine · Zantac

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.

Mechanism

GLP-1-induced slowed gastric emptying can worsen GERD; acid suppression manages the symptom.

Source: No specific FDA label warning

How to read the severity tiers

  • Contraindicated — Do not combine. The combination is either explicitly contraindicated by the FDA label or universally recognized as unsafe (e.g., two GLP-1 receptor agonists at the same time).
  • Serious — Combination is allowed but requires close monitoring or proactive dose adjustment of one of the drugs. The classic example is insulin or a sulfonylurea — both can cause hypoglycemia, and adding a GLP-1 on top requires reducing the dose of the existing diabetes medication before the first GLP-1 dose.
  • Moderate — Be aware. The interaction is real but usually does not require dose adjustment. Often involves slowed gastric emptying affecting the absorption rate (not total bioavailability) of an oral medication. Examples: warfarin, levothyroxine, oral contraceptives.
  • Minor — Generally no action needed. Either no documented interaction or the effect is clinically irrelevant (e.g., a 30-60 minute delay in acetaminophen onset).

Why GLP-1s have so many gastric-emptying interactions

GLP-1 receptor agonists slow gastric emptying as part of their mechanism of action — that's a major contributor to the satiety effect that produces weight loss. The same mechanism delays the absorption of orally administered medications by 30-60 minutes on average. For most drugs, total bioavailability (the area under the curve, AUC) is preserved, so the drug still works, but it may take slightly longer to reach peak concentration. The clinical significance is small for most medications and meaningful only for drugs with a narrow therapeutic window or a time-sensitive onset.

Hypoglycemia risk with insulin and sulfonylureas

The most clinically important GLP-1 interaction is the additive hypoglycemia risk when combined with insulin or a sulfonylurea (glipizide, glyburide, glimepiride). GLP-1s enhance glucose-dependent insulin secretion — meaning they only push insulin when blood sugar is elevated — but adding insulin or a sulfonylurea on top can produce dangerous lows. The standard protocol is to reduce the insulin dose by approximately 20% (or taper off the sulfonylurea) BEFORE the first GLP-1 dose. This should be discussed with your prescriber in advance, not after the fact.

Oral contraceptives and Foundayo

Foundayo (orforglipron, the new oral GLP-1 approved April 2026) carries a more specific drug interaction warning for oral contraceptives than the injectable GLP-1s. The Foundayo label recommends backup contraception (barrier, IUD, implant, or non-oral hormonal) for 30 days after starting the drug and 30 days after each dose increase. Women on oral birth control who plan to start any GLP-1 should discuss a backup contraception strategy with their prescriber.

What this tool is NOT

This is an educational lookup tool, not a clinical decision support system. It is not a substitute for your prescriber, your pharmacist, or a real-time interaction checker built into electronic health records. The database covers the highest-frequency clinically meaningful interactions but is not exhaustive. Always tell every prescriber and pharmacist about every medication you take, including over-the-counter products and supplements, and confirm any specific interaction with them before starting or stopping anything.

Related tools and research

Important disclaimer

This tool is for educational purposes only and does not constitute medical advice. Drug interactions are highly individual and depend on dose, timing, and your overall medication list. Weight Loss Rankings does not provide medical advice, diagnosis, or treatment recommendations. Always consult your prescribing clinician and pharmacist before combining any medication with a GLP-1 receptor agonist.

References

  1. 1.Novo Nordisk Inc. WEGOVY (semaglutide) injection — US Prescribing Information, Section 7: Drug Interactions. FDA Approved Labeling. 2025. https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/215256s024lbl.pdf
  2. 2.Novo Nordisk Inc. OZEMPIC (semaglutide) injection — US Prescribing Information, Section 7: Drug Interactions. FDA Approved Labeling. 2025. https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/209637s024lbl.pdf
  3. 3.Eli Lilly and Company. ZEPBOUND (tirzepatide) injection — US Prescribing Information, Section 7: Drug Interactions. FDA Approved Labeling. 2025. https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/217806s016lbl.pdf
  4. 4.Eli Lilly and Company. MOUNJARO (tirzepatide) injection — US Prescribing Information, Section 7: Drug Interactions. FDA Approved Labeling. 2025. https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/215866s015lbl.pdf
  5. 5.Eli Lilly and Company. FOUNDAYO (orforglipron) tablets — US Prescribing Information. FDA Approved Labeling. 2026. https://investor.lilly.com/news-releases/news-release-details/fda-approves-lillys-foundayotm-orforglipron-only-glp-1-pill
  6. 6.European Medicines Agency, Pharmacovigilance Risk Assessment Committee (PRAC). GLP-1 receptor agonists — review of psychiatric adverse events. PRAC Assessment Report. EMA. 2024. https://www.ema.europa.eu/en/news/meeting-highlights-pharmacovigilance-risk-assessment-committee-prac-8-11-april-2024