Insulin Lispro, Recombinant 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 Lispro, Recombinant
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 lisinopril (a blood pressure medicine) along with insulin lispro (Humalog) for your diagnosis. Insulin already lowers your blood sugar, and taking an ACE inhibitor like lisinopril alongside it may make your blood sugar drop a little more than expected. That could mean more moments of feeling shaky, sweaty, dizzy, or confused, which are signs of low blood sugar.
The good news is this is easy to keep an eye on. Your care team can check your sugars more closely and adjust your insulin if needed. Please don't stop or change either medicine on your own. Just talk with your doctor or pharmacist so they can tailor things for you.
Effect: Possible additive hypoglycemia when an ACE inhibitor (lisinopril) is combined with insulin lispro. Neither drug requires bioactivation, so no prodrug consideration applies here.
- Mechanism: Unknown; ACE inhibitors may enhance insulin sensitivity, potentiating insulin's glucose-lowering effect.
- Direction: Increased pharmacodynamic effect of insulin (greater hypoglycemia risk).
- Evidence: Theoretical; a self-controlled case series found no increased serious hypoglycemia with ACE inhibitors plus secretagogues, except possibly glimepiride.
- Onset: Unspecified.
- Management: More frequent glucose monitoring during therapy and after ACE inhibitor withdrawal; individualize insulin dosing.
What happens
An increased risk of hypoglycemia
Interaction Deep Dive
Using ACE inhibitors together with antidiabetic drugs can heighten the likelihood of hypoglycemia231. When these agents must be given together, glucose should be checked more often, not only throughout therapy but also once an ACE inhibitor is stopped 4. Modifications to the insulin dose might likewise become necessary 23. A self-controlled case series provides evidence that combining ACE inhibitors with insulin secretagogues does not correspond to higher rates of serious hypoglycemia, although glimepiride may be an exception 5.
Why it happens (mechanism)
Unknown
How to manage this interaction
This combination is commonly used and can be managed well. Keep taking both medications exactly as prescribed.
- Monitor your blood glucose more often, especially when starting, and also if the lisinopril is ever stopped.
- Know the signs of low blood sugar (shakiness, sweating, dizziness, confusion) and how to treat it quickly.
- Your insulin dose may need to be adjusted and individualized by your care team.
Bring your glucose readings to your pharmacist or prescriber and ask if any changes are needed. Do not change either medicine on your own.
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 covering 1999 to 2011 to assess the simultaneous use of ACE inhibitors with insulin secretagogues (glimepiride, glipizide, glyburide, nateglinide, and repaglinide) or with metformin (used as a negative control). The endpoint evaluated 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) showed no significant increase with glipizide, glyburide, repaglinide, or metformin, but was slightly raised with glimepiride (RR, 1.23; 95% CI, 1.11 to 1.37) and slightly lowered with 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 higher risk of serious hypoglycemia 5.
Common questions
Can I take Insulin Lispro, Recombinant and Lisinopril together?
Combining lisinopril with insulin lispro may slightly increase the chance of low blood sugar, so monitor your glucose more closely and let your care team adjust your insulin if needed. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Insulin Lispro, Recombinant 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 Lispro, Recombinant and Lisinopril interaction managed?
This combination is commonly used and can be managed well. Keep taking both medications exactly as prescribed. Monitor your blood glucose more often, especially when starting, and also if the lisinopril is ever stopped. Know the signs of low blood sugar (shakiness, sweating, dizziness, confusion) and how to treat it quickly. Your insulin dose may need to be adjusted and individualized by your care… 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 Lispro, Recombinant 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
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