What medication should be added to a patient with poor glycemic control (A1c of 12.5) on glipizide (glyburide) 10 mg twice daily and Metformin 850 mg three times daily?

Insulin Therapy Should Be Initiated Immediately

For a patient with A1c of 12.5% on maximally dosed oral agents (glipizide 10 mg twice daily and metformin 850 mg three times daily), basal insulin should be added as the next medication. 1

Rationale for Insulin Initiation

• The American Diabetes Association 2025 guidelines explicitly recommend insulin therapy for patients presenting with A1C >10% (>86 mmol/mol), especially when symptoms of hyperglycemia are present. 1

• With an A1c of 12.5%, this patient has severe hyperglycemia that requires the most potent glucose-lowering intervention available—insulin provides A1C reductions of 1.5-2.5%, which is necessary to approach target glycemic control. 2

• It is common practice to initiate insulin therapy for people who present with blood glucose levels ≥300 mg/dL or A1C >10%, or if the individual has symptoms of hyperglycemia (polyuria, polydipsia) or evidence of catabolism (unexpected weight loss). 1

Specific Insulin Regimen

• Start with basal insulin (NPH, glargine, detemir, or degludec) at an initial dose of 10 units daily or 0.1-0.2 units/kg, depending on the degree of hyperglycemia. 1

• Basal insulin should be prescribed in conjunction with metformin (which should be continued), and the sulfonylurea (glipizide) can be continued initially but may need dose reduction or discontinuation due to increased hypoglycemia risk when combined with insulin. 1

• Titrate the basal insulin dose based on fasting blood glucose levels, with adjustments made every 3-7 days to achieve target fasting glucose of 80-130 mg/dL. 1

Why Not Other Agents?

• GLP-1 receptor agonists or dual GIP/GLP-1 agonists could theoretically be used for severe hyperglycemia, but evidence is scarce for individuals with baseline A1C above 10-12%. 1

• SGLT2 inhibitors provide only intermediate glucose-lowering efficacy (A1C reduction of approximately 0.7-1.0%) and would be insufficient as monotherapy addition at this A1C level. 1

• DPP-4 inhibitors similarly provide only modest A1C reductions of 0.7-1.0% and would be inadequate for this degree of hyperglycemia. 2

Critical Management Considerations

• Equip the patient with an algorithm for self-titration of insulin doses based on self-monitoring of blood glucose, as this approach improves glycemic control in type 2 diabetic patients initiating insulin. 1

• Provide comprehensive education regarding self-monitoring of blood glucose, diet, exercise, and the avoidance of and response to hypoglycemia—these are critically important in any patient using insulin. 1

• Consider reducing or discontinuing glipizide once insulin is initiated to minimize hypoglycemia risk, as sulfonylureas are typically stopped once insulin regimens are used. 1

• Continue metformin unless contraindicated (eGFR <30 mL/min/1.73 m²), as it provides complementary glucose-lowering effects, cardiovascular benefits, and weight neutrality. 1, 2

Monitoring and Follow-up

• Reassess A1C in 3 months after insulin initiation to evaluate response and determine if further treatment intensification is needed. 2

• Monitor for hypoglycemia, especially if the sulfonylurea is continued alongside insulin therapy. 1

• Check vitamin B12 levels periodically, as metformin use is associated with increased risk of vitamin B12 deficiency and worsening of neuropathy symptoms. 1

Common Pitfall to Avoid

• Do not delay insulin initiation due to therapeutic inertia—with A1C at 12.5%, the patient is at significantly increased risk for both microvascular and macrovascular complications, and aggressive treatment is warranted immediately. 2

• As glucose toxicity resolves with insulin therapy, simplifying the medication plan and/or changing to noninsulin agents may become possible in the future. 1