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 17 verified interactions in the database.

Filter by severity

Showing 17 of 17 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

Serious — close monitoring

Common brand names

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

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.

Mechanism

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

Source: FDA Wegovy USPI Section 7; FDA Zepbound USPI Section 7

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: Extrapolated from the Wegovy / Zepbound PI Section 7 generic oral-medication caution (slowed gastric emptying may affect absorption of co-administered oral drugs). Warfarin INR monitoring is prudent during dose escalation.

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)

Opioid analgesics

Opioid analgesic

Moderate — be aware

Common brand names

OxyContin · Percocet · Vicodin · tramadol · Norco · Dilaudid · morphine · fentanyl patch · codeine

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.

Mechanism

Two separate motility-slowing mechanisms (opioid μ-receptor effects on enteric neurons + GLP-1 receptor agonism on enteric neurons) compound additively. Especially relevant during early titration when GLP-1 GI effects are highest.

Source: GLP-1 ileus / intestinal obstruction listed in Section 6.2 (Postmarketing Experience) of every FDA-approved GLP-1 label. No formal PK study of opioid + GLP-1 combination has been published; this is mechanism-based clinical guidance per ASA perioperative recommendations and the same FDA postmarketing signal.

Benzodiazepines (alprazolam, lorazepam)

Benzodiazepine

Moderate — be aware

Common brand names

Xanax · alprazolam · Ativan · lorazepam · Klonopin · clonazepam · Valium · diazepam · Restoril · temazepam

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.

Mechanism

Benzodiazepines are highly lipophilic. Reduced fat compartment with rapid weight loss → smaller distribution volume → higher relative plasma concentration at the same milligram dose.

Source: PMC12052016 review on benzodiazepine pharmacokinetics in weight-loss contexts. No GLP-1-cohort-specific PK study has been published; mechanism applies to any rapid-weight-loss context.

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

NSAIDs (ibuprofen, naproxen, celecoxib)

Non-steroidal anti-inflammatory drug (NSAID)

Minor — generally safe

Common brand names

Advil · Motrin · ibuprofen · Aleve · naproxen · Celebrex · celecoxib · Mobic · meloxicam

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.

Mechanism

Delayed gastric emptying alters absorption kinetics of orally administered NSAIDs without reducing total bioavailability.

Source: FDA Section 7.2 of every GLP-1 label (general delayed-gastric-emptying caution). Hooper et al, Pharmacotherapy 2025 (PMID 39989027) PBPK modeling supports preserved AUC. No GLP-1-cohort-specific PK study of NSAIDs has been published; mechanism-plausible only.

Oral antibiotics

Oral antibiotic

Minor — generally safe

Common brand names

amoxicillin · Augmentin · azithromycin · Z-Pak · doxycycline · ciprofloxacin · Cipro · clindamycin · cephalexin · Keflex

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.

Mechanism

Class-level FDA Section 7.2 caution for any oral medication co-administered with a drug that delays gastric emptying. No antibiotic-specific PK study has been published.

Source: FDA Section 7.2 of every GLP-1 label (general oral-medication caution). No formal PK study of any specific antibiotic + GLP-1 combination has been published; class-level mechanism-based guidance only.

Atypical antipsychotics (olanzapine, quetiapine)

Atypical antipsychotic

Minor — generally safe

Common brand names

Zyprexa · olanzapine · Seroquel · quetiapine · Risperdal · risperidone · Abilify · aripiprazole · Clozaril · clozapine

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.

Mechanism

GLP-1 effects on appetite and gastric emptying counteract the appetite-stimulating and weight-gain effects of atypical antipsychotics. The two work on different physiological pathways without pharmacokinetic interference.

Source: Systematic reviews PMC10265718 + PMC12528064 on GLP-1 receptor agonists in antipsychotic-induced weight gain. No clinically significant DDI documented; mechanism-supported beneficial combination.

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/2025/215256s026lbl.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/2025/209637s035,209637s037lbl.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/2026/217806s002lbl.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/2025/215866s039lbl.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