Glipizide and metformin and Tirzepatide interaction
Glipizide and metformin and Tirzepatide: both prescribing labels flag this combination with the strongest language, such as a contraindication, a boxed warning, or an instruction to avoid it.
Do not combine without a prescriber's guidance. The label language below is the strongest FDA uses.
What the FDA labels say
From the Glipizide and metformin (Glipizide and Metformin Hydrochloride) label · effective 2026-06-27
Diabetic ketoacidosis should be treated with insulin.
WARNINGS SPECIAL WARNING ON INCREASED RISK OF CARDIOVASCULAR MORTALITY The administration of oral hypoglycemic drugs has been reported to be associated with increased cardiovascular mortality as compared to treatment with diet alone or diet plus insulin.
This warning is based on the study conducted by the University Group Diabetes Program (UGDP), a long-term prospective clinical trial designed to evaluate the effectiveness of glucose-lowering drugs in preventing or delaying vascular complications in patients with non-insulin-dependent diabetes.
The risk of hypoglycemia is increased when caloric intake is deficient, when strenuous exercise is not compensated by caloric supplementation, or during concomitant use with other glucose-lowering agents or ethanol.
Macrovascular Outcomes There have been no clinical studies establishing conclusive evidence of macrovascular risk reduction with glipizide and metformin hydrochloride or any other antidiabetic drug.
From the Tirzepatide (Zepbound) label · effective 2026-08-28
Hypoglycemia: Concomitant use with insulin or an insulin secretagogue may increase the risk of hypoglycemia, including severe hypoglycemia.
Reducing dose of insulin or insulin secretagogue may be necessary.
In this trial, patients taking ZEPBOUND in combination with an insulin secretagogue (e.g., sulfonylurea) had increased risk of hypoglycemia (10.3%) compared to ZEPBOUND-treated patients not taking a sulfonylurea (2.1%).
The risk of hypoglycemia may be lowered by a reduction in the dose of insulin or sulfonylurea (or other concomitantly administered insulin secretagogue).
When initiating ZEPBOUND, consider reducing the dose of concomitantly administered insulin or insulin secretagogues (e.g., sulfonylureas) to reduce the risk of hypoglycemia [see Warnings and Precautions ( 5.7 )] .
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Open in the checkerNot medical advice. Interaction Checker quotes FDA label text and NIH fact sheets. Whether an interaction matters for you depends on doses, timing, kidney and liver function, and other conditions. Confirm with a pharmacist or prescriber.