Lisinopril and Sitagliptin: 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
Sitagliptin
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've been prescribed sitagliptin (Januvia) for blood sugar and lisinopril (an ACE inhibitor) for blood pressure. Both are very common, and it's fine to take them together. The one thing to know is that ACE inhibitors like lisinopril can sometimes make blood sugar medicines work a little harder, which could lower your blood sugar more than expected.
This is mostly a theoretical concern, so please don't worry. It just means it's smart to check your blood sugar a bit more often, especially when you first start or stop lisinopril. If you feel shaky, sweaty, or lightheaded, let your care team know. They can easily adjust things and keep you safe.
Effect: Possible increased risk of hypoglycemia with concomitant ACE inhibitor (lisinopril) and antidiabetic agent (sitagliptin, a DPP-4 inhibitor).
Mechanism: Unknown; proposed enhancement of insulin sensitivity/glucose uptake with ACE inhibition. Neither agent is enzymatically dependent in a way that changes direction here.
Evidence: Theoretical. A self-controlled case series found no increased serious hypoglycemia with ACE inhibitors plus insulin secretagogues (possible exception: glimepiride). Onset unspecified.
- Monitor blood glucose more frequently during initiation and after withdrawal of lisinopril.
- Individualize antidiabetic dosing per glycemic response.
- Sitagliptin monotherapy carries low intrinsic hypoglycemia risk.
What happens
An increased risk of hypoglycemia
Interaction Deep Dive
Taking ACE inhibitors together with antidiabetic drugs can heighten the likelihood of hypoglycemia231. When these agents must be used together, glucose levels should be checked more often, not only throughout treatment but also once an ACE inhibitor is discontinued 4. It may also be necessary to modify insulin dosing 23. Findings from a self-controlled case series indicate that combining ACE inhibitors with insulin secretagogues does not raise the incidence of serious hypoglycemia, although glimepiride may be an exception 5.
Why it happens (mechanism)
Unknown
How to manage this interaction
Keep taking both medications exactly as prescribed. This is a low-level, mostly theoretical concern, and your care team can manage it easily.
- Check your blood sugar a bit more often, especially when you first start lisinopril or if it is stopped.
- Watch for low blood sugar signs: shakiness, sweating, dizziness, confusion, or hunger.
- Your diabetes medication dose may need to be adjusted and individualized by your team based on your readings.
Talk with your pharmacist or doctor before changing anything, and report 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) In a self-controlled case series, Medicare claims records from 5 states covering 1999 to 2011 were examined for the joint use of ACE inhibitors together with insulin secretagogues (glimepiride, glipizide, glyburide, nateglinide, and repaglinide) or metformin (used as a negative control). The endpoint assessed was hospital presentation for serious hypoglycemia. During the observation period, the number of serious hypoglycemic events was 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 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 an increased risk of serious hypoglycemia 5.
Common questions
Can I take Lisinopril and Sitagliptin together?
Taking sitagliptin with lisinopril may slightly raise the chance of low blood sugar, so monitor your glucose a little more closely, especially when starting or stopping lisinopril. Report any symptoms of low blood sugar to your care team. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Lisinopril and Sitagliptin 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 Sitagliptin interaction managed?
Keep taking both medications exactly as prescribed. This is a low-level, mostly theoretical concern, and your care team can manage it easily. Check your blood sugar a bit more often, especially when you first start lisinopril or if it is stopped. Watch for low blood sugar signs: shakiness, sweating, dizziness, confusion, or hunger. Your diabetes medication dose may need to be adjusted and individu… 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 Sitagliptin 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 Sitagliptin
Keep reading about Lisinopril
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