Insulin Glulisine and Lisinopril: 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
Lisinopril
Insulin Glulisine
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.
Taking lisinopril with your Apidra insulin can slightly raise the chance of low blood sugar (hypoglycemia). Lisinopril is a blood pressure medicine, and Apidra is a fast-acting insulin that already lowers your blood sugar. When they are used together, your sugar may dip a bit more than expected. You might feel shaky, sweaty, dizzy, or hungry if it drops too low.
The good news is this is very manageable. Please keep taking both medicines as prescribed. Your care team can check your blood sugar more often and adjust your insulin dose if needed, especially right after any change to your blood pressure medicine. Let them know if you notice frequent low readings.
Effect: Possible additive risk of hypoglycemia when an ACE inhibitor (lisinopril) is combined with insulin glulisine.
- Direction: Enhanced glucose-lowering / increased hypoglycemia risk. Neither agent is a prodrug relevant here.
- Mechanism: Unknown; proposed increased insulin sensitivity with ACE inhibition (PD interaction, not a clear PK/enzyme effect).
- Evidence: Theoretical; a self-controlled case series found no increased serious hypoglycemia with ACE inhibitors plus insulin secretagogues (possible exception: glimepiride).
- Onset: Unspecified.
- Management: More frequent glucose monitoring during concomitant use and after ACE inhibitor withdrawal; individualize insulin dosing as needed.
What happens
An increased risk of hypoglycemia
Interaction Deep Dive
Taking ACE inhibitors together with antidiabetic medications may heighten the likelihood of hypoglycemia231. When these agents must be used together, glucose levels should be checked more frequently, both throughout treatment and following discontinuation of an ACE inhibitor 4. It may also become necessary to modify the insulin dose 23. 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 an exception 5.
Why it happens (mechanism)
Unknown
How to manage this interaction
Keep taking both medicines as prescribed unless your prescriber tells you otherwise. This combination is commonly used and can be managed safely.
- Expect your care team to monitor your blood sugar more closely, both while you take both drugs and if your lisinopril is ever stopped.
- Your insulin dose may need to be adjusted and individualized by your team based on your readings.
- Learn the signs of low blood sugar (shakiness, sweating, confusion, hunger) and how to treat it quickly.
- Tell your pharmacist or doctor if you have frequent or unexplained lows.
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 from 5 states collected 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 outcome 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 increased 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 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 Insulin Glulisine and Lisinopril together?
Combining lisinopril with Apidra insulin may modestly increase the chance of low blood sugar, so check your glucose more often and let your care team adjust your insulin if needed. Keep taking both as prescribed. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Insulin Glulisine and Lisinopril 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 Insulin Glulisine and Lisinopril interaction managed?
Keep taking both medicines as prescribed unless your prescriber tells you otherwise. This combination is commonly used and can be managed safely. Expect your care team to monitor your blood sugar more closely, both while you take both drugs and if your lisinopril is ever stopped. Your insulin dose may need to be adjusted and individualized by your team based on your readings. Learn the signs of lo… 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 Insulin Glulisine or Lisinopril 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 Lisinopril
Keep reading about Insulin Glulisine
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