Lisinopril and Glyburide: Interaction Details
AI-assisted, pharmacist-reviewed · AI content regenerated Jul 11, 2026 · Source data updated Jul 2, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Glyburide
Lisinopril
How we grade severity & evidence
Severity levels
- Contraindicated: These should generally not be used together.
- Major: Potentially serious — often needs a change or close monitoring.
- Moderate: Can be significant — usually manageable with monitoring.
- Minor: Usually limited clinical impact.
Evidence grades
- Established: Well documented — supported by controlled studies or strong clinical data.
- Probable: Good supporting evidence, though not definitively proven.
- Suspected: Some evidence suggests this interaction, but it is not well established.
- Possible: Limited or conflicting evidence; the interaction may occur.
- Theoretical: Predicted from the drugs' pharmacology; not yet confirmed in people.
Ratings come from the documented interaction literature and are reviewed by a pharmacist. They describe the documented risk of the combination, not what will necessarily happen to you — your dose, timing, and health picture all matter.
You're taking glyburide to lower your blood sugar and lisinopril for your blood pressure. When these two are used together, there's a chance your blood sugar could dip a little lower than usual. That means you might notice signs of low blood sugar (hypoglycemia) like shakiness, sweating, dizziness, or feeling hungry or confused.
The good news is this is a well-known combination that many people take safely. This warning is based mostly on theory, not strong proof. Your care team can manage it easily by checking your blood sugar a bit more often. Keep taking both as prescribed, and let your doctor or pharmacist know if you feel any low-sugar symptoms.
Effect: Potential additive increase in hypoglycemia risk when the ACE inhibitor lisinopril is combined with the sulfonylurea glyburide (an insulin secretagogue).
Mechanism: Unknown; proposed enhancement of insulin sensitivity by ACE inhibitors. This is a pharmacodynamic, not a CYP-mediated interaction. Neither agent's clearance drives the effect.
Evidence: Theoretical. A self-controlled case series found no increase in serious hypoglycemia with ACE inhibitors plus secretagogues, with the possible exception of glimepiride.
- Onset unspecified; severity moderate.
- Increase glucose self-monitoring during ACE inhibitor initiation and after withdrawal.
- Individualize antidiabetic dosing as needed.
What happens
An increased risk of hypoglycemia
Interaction Deep Dive
The concurrent administration of ACE inhibitors alongside antidiabetic drugs can elevate the likelihood of hypoglycemia231. When these agents must be used together, glucose levels should be checked more often, both throughout therapy and following discontinuation of an ACE inhibitor4. Adjustments to insulin dosing may likewise be required23. Findings from a self-controlled case series indicate that combining ACE inhibitors with insulin secretagogues does not correlate with higher rates of serious hypoglycemia, although glimepiride may be a possible exception5.
Why it happens (mechanism)
Unknown
How to manage this interaction
This combination is used commonly and can be managed well by your care team.
- Keep taking both medications as prescribed unless your doctor tells you otherwise.
- Your team may check your blood sugar more often, especially when lisinopril is first started and also if it is ever stopped.
- Your glyburide dose may need to be adjusted and individualized by your prescriber based on your readings.
- Know the signs of low blood sugar (shaking, sweating, dizziness, confusion) and treat them promptly.
Bring your glucose logs to appointments and raise any low-sugar episodes with your pharmacist or prescriber.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
1 report — tap to read
a) A self-controlled case series examined Medicare claims data drawn from 5 states between 1999 and 2011 to assess the combined use of ACE inhibitors with insulin secretagogues (glimepiride, glipizide, glyburide, nateglinide, and repaglinide) or with metformin (serving as a negative control). The endpoint assessed was hospital presentation for serious hypoglycemia. During the observation period, the counts of serious hypoglycemic events were 8159, 14,353, 11,129, 1595, 2901, and 32,639 for glimepiride, glipizide, glyburide, nateglinide, repaglinide, and metformin, respectively. The confounder-adjusted rate ratio (RR) was not significantly increased for glipizide, glyburide, repaglinide, or metformin, but was slightly increased for glimepiride (RR, 1.23; 95% CI, 1.11 to 1.37) and slightly decreased for nateglinide (RR, 0.73; 95% CI, 0.56 to 0.96). Apart from glimepiride, these findings indicate that concurrent use of an ACE inhibitor and insulin secretagogues was not linked to a greater risk of serious hypoglycemia 5.
Common questions
Can I take Lisinopril and Glyburide together?
Taking glyburide with lisinopril may slightly raise your chance of low blood sugar, so check your glucose a bit more often (especially when starting or stopping the lisinopril) and keep taking both as prescribed. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Lisinopril and Glyburide interaction?
It is rated moderate. Can be significant — usually manageable with monitoring.
How quickly could this interaction happen?
The documented onset is "unspecified". The timing of this interaction is not well characterized.
How is the Lisinopril and Glyburide interaction managed?
This combination is used commonly and can be managed well by your care team. Keep taking both medications as prescribed unless your doctor tells you otherwise. Your team may check your blood sugar more often, especially when lisinopril is first started and also if it is ever stopped. Your glyburide dose may need to be adjusted and individualized by your prescriber based on your readings. Know the… Management is individual — always follow your own care team's guidance.
How strong is the evidence for this interaction?
The evidence is graded "theoretical". Predicted from the drugs' pharmacology; not yet confirmed in people.
From our Q&A
Real reader questions about these medications, each personally answered by our pharmacist:
Questions for your pharmacist
- Does my dose of Lisinopril or Glyburide need adjusting while I take them together?
- What symptoms should prompt me to call you or my prescriber right away?
- Does the timing of my doses matter for this combination?
- Is there anything you'd monitor while I'm on both?
References (5)
- Product Information: Zestril(R) oral tablets, lisinopril oral tablets. AstraZeneca Pharmaceuticals LP (per FDA), Wilmington, DE, 2014. DailyMed
- Product Information: TOUJEO(R) subcutaneous injection, insulin glargine subcutaneous injection. sanofi-aventis (per manufacturer), Bridgewater, NJ, 2015. DailyMed
- Product Information: AFREZZA(R) oral inhalation powder, insulin human oral inhalation powder. MannKind Corporation(TM) (per manufacturer), Danbury, CT, 2014. DailyMed
- Product Information: AMARYL(R) oral tablets, glimepiride oral tablets. Sanofi-Aventis U.S. LLC (per FDA), Bridgewater, NJ, 2013. DailyMed
- Hee Nam Y, Brensinger CM, Bilker WB, et al: Angiotensin-converting enzyme inhibitors used concomitantly with insulin secretagogues and the risk of serious hypoglycemia. Clin Pharmacol Ther 2022; 111(1):218-226. PubMed
Keep reading about Glyburide
Keep reading about Lisinopril
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