What's the next step for a female patient with diabetes, hypertension, and hyperlipidemia, who has an unchanged Hemoglobin A1c (HbA1c) level of 8.0% despite being on Jardiance (Empagliflozin) 25 mg once daily, Ozempic (Semaglutide) 2 mg subcutaneously once a week, Glipizide (Glipizide) ER 15 mg total once a day, and metformin (Metformin) 1000 mg twice a day with an additional half tablet at noon, and also has Restless Legs Syndrome and mildly impaired renal function with an estimated Glomerular Filtration Rate (eGFR) of 83?

Treatment Intensification for Uncontrolled Type 2 Diabetes

Discontinue glipizide and add basal insulin to the current regimen of metformin, Jardiance, and Ozempic. 1, 2

Rationale for Discontinuing Glipizide

• Sulfonylureas should be discontinued when moving beyond simple oral therapy regimens, particularly when adding insulin or intensifying to more complex regimens, as the combination significantly increases hypoglycemia risk (24% rate with sulfonylureas) without providing substantial additional glycemic benefit. 1, 2

• The patient's HbA1c has remained unchanged at 8.0% despite being on maximum-dose Ozempic (2 mg weekly), indicating that the current oral/injectable regimen has reached its therapeutic ceiling. 1

• Glipizide contributes minimal additional benefit at this stage while substantially increasing hypoglycemia risk, especially when combined with insulin therapy. 3, 2

Initiating Basal Insulin

• Start basal insulin at 10 units daily or 0.1-0.2 units/kg body weight, administered once daily at bedtime. 3, 1, 2

• Titrate the basal insulin dose by 2 units every 3 days until fasting blood glucose consistently reaches 80-130 mg/dL without hypoglycemia. 3, 1, 2

• The maximum basal insulin dose should not exceed approximately 0.5 units/kg/day to avoid overbasalization. 1

• Continue metformin as the foundation of therapy due to its established efficacy, safety profile, cardiovascular benefits, and ability to reduce insulin requirements when used in combination. 3, 1, 2

Maintaining Current Effective Agents

• Continue Jardiance (empagliflozin) 25 mg daily for its proven cardiovascular and renal protective benefits, independent of glycemic control, particularly important given this patient's hypertension and hyperlipidemia. 3, 4

• The EMPA-REG OUTCOME trial demonstrated that empagliflozin reduced cardiovascular death (HR 0.62), heart failure hospitalization (HR 0.65), and all-cause mortality (HR 0.68) in patients with type 2 diabetes and cardiovascular risk factors. 3

• Continue Ozempic (semaglutide) 2 mg weekly as it provides superior HbA1c reduction compared to insulin intensification alone (0.6-0.8% additional reduction), causes weight loss rather than weight gain, and has minimal hypoglycemia risk. 3, 1, 5

• The combination of metformin, SGLT2 inhibitor, GLP-1 receptor agonist, and basal insulin addresses multiple pathophysiologic defects in type 2 diabetes while minimizing adverse effects. 1

Monitoring Requirements

• Check fasting blood glucose daily during insulin titration to guide dose adjustments and prevent hypoglycemia. 1, 2

• Reassess HbA1c in 3 months to evaluate treatment effectiveness and determine if further intensification is needed. 3, 1, 2

• Provide comprehensive patient education on insulin injection technique, self-monitoring of blood glucose, hypoglycemia recognition and treatment, and supply hypoglycemia treatment materials. 2

• Monitor renal function periodically, as both metformin and Jardiance require dose adjustment if kidney function declines (metformin contraindicated if eGFR <30 mL/min, Jardiance less effective if eGFR <45 mL/min). 1, 6

If HbA1c Remains Above Goal After Basal Insulin Optimization

• If HbA1c remains >7% after 3-6 months despite optimized basal insulin (defined as fasting glucose at target or dose reaching 0.5 units/kg/day), add rapid-acting prandial insulin before the largest meal. 3, 1, 2

• Start prandial insulin at 4 units or 10% of the basal insulin dose, and increase by 1-2 units or 10-15% twice weekly based on 2-hour postprandial glucose readings. 1, 2

Important Caveats

• The patient's eGFR of 83 mL/min is adequate for all current medications, but requires periodic monitoring as both metformin and Jardiance have renal dosing considerations. 1, 6

• Delaying treatment intensification beyond 3 months at HbA1c above target increases complication risk, and medication adjustments should be made promptly. 1

• When switching from glipizide to insulin, educate the patient that hypoglycemia symptoms may differ, and that basal insulin carries lower hypoglycemia risk than sulfonylureas when properly titrated. 2

• Research demonstrates that when glucose-lowering therapy shows limited initial response, continuing the ineffective agent while adding new therapy produces better outcomes than switching agents. 7