Lisinopril and Chlorpropamide: 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
Chlorpropamide
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.
What this means for you: Chlorpropamide (Diabinese) is a diabetes pill that lowers your blood sugar by helping your body release insulin. Lisinopril (Prinivil, Zestril) is a blood pressure medicine that, in some people, may make blood sugar drop a little more than usual. Put together, there's a chance your blood sugar could go too low (hypoglycemia). That can feel like shakiness, sweating, dizziness, or confusion.
The good news is this is easy to keep an eye on. Please don't stop either medicine on your own. Your care team can check your blood sugar more often and adjust things if needed. Just let them know if you feel low.
Effect: Possible additive increase in hypoglycemia risk when the ACE inhibitor lisinopril is combined with the sulfonylurea chlorpropamide (an insulin secretagogue). Neither is a prodrug in a way that reverses direction here.
- Mechanism: Unknown; ACE inhibitors may enhance insulin sensitivity/glucose uptake, augmenting the secretagogue's effect.
- Direction: Enhanced pharmacodynamic glucose-lowering effect.
- Evidence: Theoretical; a self-controlled case series found no increase in serious hypoglycemia with ACE inhibitors plus secretagogues (possible exception: glimepiride).
- Onset: Unspecified.
- Management: More frequent glucose monitoring during therapy and after ACE inhibitor withdrawal; individualize antidiabetic dosing.
What happens
An increased risk of hypoglycemia
Interaction Deep Dive
Taking ACE inhibitors together with antidiabetic medications can heighten the likelihood of hypoglycemia231. When these drugs must be used together, glucose should be checked more often, throughout treatment as well as following discontinuation of an ACE inhibitor 4. Modifications to the insulin dose might also be required 23. According to findings from a self-controlled case series, combining ACE inhibitors with insulin secretagogues does not appear to raise the incidence of serious hypoglycemia, although glimepiride may be an exception 5.
Why it happens (mechanism)
Unknown
How to manage this interaction
How to manage this safely: This combination is used often and is generally manageable. Keep taking both medicines exactly as prescribed unless your prescriber tells you otherwise.
- Your care team may check your blood sugar more often, both while you're on both drugs and after the lisinopril is stopped.
- Your chlorpropamide dose may need to be adjusted and individualized by your team.
- Learn the signs of low blood sugar (shakiness, sweating, dizziness, confusion) and keep a fast sugar source handy.
Tell your pharmacist or doctor about any low-blood-sugar episodes so they can fine-tune your plan.
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 collected from 5 states between 1999 and 2011 to evaluate 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 raised for glipizide, glyburide, repaglinide, or metformin, but was slightly raised for glimepiride (RR, 1.23; 95% CI, 1.11 to 1.37) and slightly lowered for nateglinide (RR, 0.73; 95% CI, 0.56 to 0.96). Apart from glimepiride, these findings indicate that combined use of an ACE inhibitor and insulin secretagogues was not linked to an increased risk of serious hypoglycemia 5.
Common questions
Can I take Lisinopril and Chlorpropamide together?
Combining chlorpropamide with lisinopril may slightly raise the chance of low blood sugar, so monitor your glucose more closely and report any lows to your care team. Do not change either medicine on your own. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Lisinopril and Chlorpropamide 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 Chlorpropamide interaction managed?
How to manage this safely: This combination is used often and is generally manageable. Keep taking both medicines exactly as prescribed unless your prescriber tells you otherwise. Your care team may check your blood sugar more often, both while you're on both drugs and after the lisinopril is stopped. Your chlorpropamide dose may need to be adjusted and individualized by your team. Learn the signs… 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 Chlorpropamide 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 Chlorpropamide
Keep reading about Lisinopril
These medications also interact with supplements
Prescription drugs aren't the whole picture — herbal and dietary supplements can interact with them too. From the evidence-graded Natural Medicines database:
major · moderate · minor — check everything you take with our drug–supplement interaction checker.
Check another combination
Our instant two-drug interaction checker is almost here.
Still have questions about this combination?
Every question gets a real answer from a licensed pharmacist — free, and usually within a day.
Ask the pharmacist