Insulin Degludec 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 Degludec
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.
Both of these are common medicines. Lisinopril (Prinivil, Zestril) lowers blood pressure, and insulin degludec (Tresiba) is a long-acting insulin that lowers your blood sugar. When they are taken together, there is a chance your blood sugar could drop a little lower than expected, which is called hypoglycemia. You might feel shaky, sweaty, dizzy, or very hungry.
The good news is this is easy to keep an eye on. The evidence here is mostly theoretical, so please don't worry. Keep taking both as prescribed, check your blood sugar as your team advises, and let your pharmacist or doctor know if you notice low-sugar symptoms. They can adjust things for you.
Effect: Additive risk of hypoglycemia when an ACE inhibitor (lisinopril) is combined with insulin degludec.
- Direction: Increased hypoglycemic effect of insulin. Neither agent is a prodrug relevant to this interaction.
- Mechanism: Unknown; proposed enhancement of insulin sensitivity with ACE inhibition. Pharmacodynamic rather than a defined PK change.
- 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 coadministration and after ACE inhibitor withdrawal. Insulin dose may need individualization.
What happens
An increased risk of hypoglycemia
Interaction Deep Dive
Using ACE inhibitors together with antidiabetic medications can raise the likelihood of hypoglycemia231. When these agents must be given together, glucose levels should be checked more often, both throughout therapy and following discontinuation of an ACE inhibitor4. It may also be necessary to modify the insulin dose23. 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 exception5.
Why it happens (mechanism)
Unknown
How to manage this interaction
This combination can usually be managed safely. Keep taking both lisinopril and insulin degludec exactly as prescribed unless your prescriber tells you otherwise.
- Your care team may ask you to check your blood sugar more often, both while on both drugs and if your lisinopril is ever stopped.
- Your insulin dose may need to be adjusted and individualized by your care team based on your readings.
- Learn the signs of low blood sugar (shakiness, sweating, confusion, hunger) and treat quickly with fast-acting sugar.
- Tell your pharmacist or doctor if you have frequent lows or any new symptoms.
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 simultaneous use of ACE inhibitors with insulin secretagogues (glimepiride, glipizide, glyburide, nateglinide, and repaglinide) or 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) showed no significant elevation with glipizide, glyburide, repaglinide, or metformin, but was slightly elevated with glimepiride (RR, 1.23; 95% CI, 1.11 to 1.37) and slightly reduced 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 an increased risk of serious hypoglycemia 5.
Common questions
Can I take Insulin Degludec and Lisinopril together?
Taking lisinopril with insulin degludec may slightly raise your chance of low blood sugar, so keep both as prescribed and monitor your glucose a bit more closely, especially if the lisinopril is started or stopped. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Insulin Degludec 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 Degludec and Lisinopril interaction managed?
This combination can usually be managed safely. Keep taking both lisinopril and insulin degludec exactly as prescribed unless your prescriber tells you otherwise. Your care team may ask you to check your blood sugar more often, both while on both drugs and if your lisinopril is ever stopped. Your insulin dose may need to be adjusted and individualized by your care team based on your readings. Lear… 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 Degludec 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 Degludec
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