Is it reasonable to stop glipizide (a sulfonylurea) in a patient with well-controlled diabetes and a hemoglobin A1C (HbA1C) of 5.8 who is also taking metformin (a biguanide) and Mounjaro (tirzepatide) until the next HbA1C check?

Discontinuing Glipizide in Well-Controlled Diabetes

Yes, it is reasonable and advisable to discontinue glipizide in this patient with an A1C of 5.8% who is also taking metformin and Mounjaro (tirzepatide), as continuing the sulfonylurea poses unnecessary hypoglycemia risk without additional benefit. 1

Rationale for Stopping Glipizide

The patient's A1C of 5.8% is well below the recommended target of <7% for most adults with diabetes, indicating potential overtreatment. 1 The American College of Physicians guidance emphasizes that glycemic control should be "as low as is feasible without undue risk for adverse events," and an A1C of 5.8% in a patient on three glucose-lowering agents creates substantial hypoglycemia risk. 1

Hypoglycemia Risk with Sulfonylureas

• Glipizide is a sulfonylurea that carries significant hypoglycemia risk, particularly when combined with other glucose-lowering agents. 1, 2
• The FDA label for glipizide explicitly warns about hypoglycemia risk and notes that dose adjustment is required when adding new agents to patients at or near glycemic goals. 2
• When patients on sulfonylureas are combined with GLP-1 receptor agonists like Mounjaro, dose reduction or discontinuation of the sulfonylurea is necessary to avoid hypoglycemia. 1

Mounjaro (Tirzepatide) Provides Superior Glycemic Control

• Mounjaro is a dual GIP/GLP-1 receptor agonist that typically reduces A1C by 1-2% when added to metformin, which is substantially more potent than sulfonylureas. 1
• The 2025 American Diabetes Association Standards recommend GLP-1 receptor agonists (and dual GIP/GLP-1 agonists like Mounjaro) as preferred agents over sulfonylureas due to superior efficacy, cardiovascular benefits, weight loss effects, and lower hypoglycemia risk. 1
• Current guidelines do not recommend using sulfonylureas alongside GLP-1 receptor agonists when glycemic targets are already achieved. 1

Practical Implementation

Discontinue glipizide immediately rather than tapering, as sulfonylureas do not require gradual withdrawal. 2

Monitoring Plan

• Check fasting and pre-meal blood glucose values for 1-2 weeks after discontinuation to ensure glycemic control remains adequate. 2
• Recheck A1C in 3 months to confirm continued glycemic control without the sulfonylurea. 1, 3
• If A1C rises above the individualized target (typically <7%), consider optimizing metformin dose to maximum effective dose (2000 mg daily) before adding back any additional agents. 1, 3

Patient Education Points

• Inform the patient that stopping glipizide reduces their risk of dangerous low blood sugar episodes. 2
• Emphasize that Mounjaro and metformin are sufficient to maintain excellent glycemic control with lower risk. 1
• Instruct the patient to monitor for symptoms of hyperglycemia (increased thirst, urination, fatigue) and report if they occur, though this is unlikely given the potency of their remaining regimen. 2

Common Pitfalls to Avoid

• Do not continue glipizide "just in case" or out of therapeutic inertia - the hypoglycemia risk outweighs any theoretical benefit when A1C is already 5.8%. 1
• Do not taper the glipizide dose - sulfonylureas can be stopped abruptly without withdrawal effects, and tapering only prolongs unnecessary hypoglycemia risk. 2
• Do not wait until the next A1C check to make this decision - the current A1C of 5.8% already provides sufficient evidence that the patient is overtreated. 1
• Avoid adding back sulfonylureas if A1C rises slightly - optimize metformin dosing first, as it has superior safety profile and cardiovascular benefits compared to sulfonylureas. 1