What is the best treatment option for a patient with poorly controlled type 2 diabetes (T2D) and elevated hemoglobin A1c (HbA1c), currently on metformin and insulin, considering the addition of Jardiance (empagliflozin)?

Adding Jardiance (Empagliflozin) to Metformin and Insulin in Type 2 Diabetes

Add empagliflozin 10 mg once daily to your patient's current metformin and insulin regimen, and reduce the insulin dose by approximately 20% at initiation to prevent hypoglycemia. 1

Primary Rationale for Addition

Empagliflozin is specifically recommended by the European Society of Cardiology for patients with type 2 diabetes and cardiovascular disease or very high/high cardiovascular risk to reduce cardiovascular events and mortality. 1 This recommendation stands independent of baseline HbA1c level, meaning even if glycemic control improves, the cardiovascular and renal benefits justify continuation. 1, 2

• The cardiovascular mortality reduction observed with empagliflozin occurs within months of initiation and appears related to heart failure prevention rather than prevention of atherosclerotic events like myocardial infarction or stroke. 3
• Empagliflozin reduces hospitalization for heart failure, which is particularly valuable in patients with existing cardiovascular risk factors. 1

Expected Glycemic Benefit

Expect an additional HbA1c reduction of 0.5-0.8% when adding empagliflozin to metformin and insulin. 2, 4

• The glucose-lowering effect is moderate compared to GLP-1 receptor agonists but provides meaningful improvement in poorly controlled patients. 2
• Efficacy decreases with declining renal function: expect -0.6% HbA1c reduction if eGFR 60-90 mL/min/1.73 m², -0.5% if eGFR 45-60, and only -0.2% if eGFR 30-45. 2
• Do not use empagliflozin for glycemic control if eGFR <45 mL/min/1.73 m², though it may still be continued for cardiovascular/renal protection down to eGFR ≥25 in patients with established cardiovascular disease. 2

Additional Non-Glycemic Benefits

Beyond glucose lowering, empagliflozin provides:

• Weight reduction of approximately 2-3 kg compared to placebo, which contrasts favorably with the weight gain typically seen with insulin intensification. 4, 5
• Systolic blood pressure reduction of 3-4 mmHg and diastolic reduction of approximately 2 mmHg. 4, 5
• These benefits occur through osmotic diuresis and calorie loss via glucosuria. 5

Critical Safety Modifications at Initiation

Reduce insulin dose by 20% when adding empagliflozin to prevent hypoglycemia as glycemic control improves. 1, 2

• If the patient is also on a sulfonylurea, consider weaning or stopping it entirely rather than dose reduction. 1
• Avoid substantial initial insulin reductions >20%, as this increases diabetic ketoacidosis risk. 1
• Monitor for hypoglycemia more frequently in the first 2-4 weeks after adding empagliflozin. 1

Monitoring Requirements and Safety Concerns

Counsel patients about increased risk of genital mycotic infections (especially in women) and emphasize meticulous personal hygiene. 1, 3

• Topical antifungal agents are first-line for genital infections; oral antifungals require attention to QTc prolongation if patient takes antiarrhythmics. 1
• Educate about euglycemic diabetic ketoacidosis symptoms (nausea, vomiting, abdominal pain, weakness) and instruct to seek immediate care if these develop. 1
• Check renal function before initiation and monitor periodically, as empagliflozin's diuretic effect can precipitate volume depletion and acute kidney injury, especially with concurrent nephrotoxic drugs or other diuretics. 1, 3

Monitor for volume depletion and hypotension, particularly in elderly patients or those on other antihypertensives/diuretics. 1, 3

• Consider temporarily holding empagliflozin during acute illness with reduced oral intake or volume loss. 1

Dosing Strategy

Start with empagliflozin 10 mg once daily; no dose titration beyond 10 mg is necessary for cardiovascular risk reduction. 2

• The 25 mg dose provides marginally greater HbA1c reduction (approximately 0.1-0.2% more) but offers no additional cardiovascular benefit. 2, 4
• For purely glycemic indications in patients without cardiovascular disease, the 25 mg dose may be considered if HbA1c remains >7% after 12 weeks on 10 mg. 4

Continuation of Metformin

Continue metformin throughout treatment as recommended by the American Diabetes Association, even when insulin and empagliflozin are added. 6

• Metformin provides weight neutrality, reduces insulin requirements by approximately 6.6 units/day, and improves lipid profiles when combined with insulin. 6, 7
• The combination of metformin, insulin, and empagliflozin is explicitly supported by guidelines, with no evidence of negative interactions. 6, 4
• Check vitamin B12 levels annually in patients on long-term metformin. 6

Reassessment Timeline

Recheck HbA1c at 3 months to assess response to the triple therapy regimen. 6

• If HbA1c remains >7% despite adherence, consider adding a GLP-1 receptor agonist, which provides greater glycemic potency than empagliflozin and additional cardiovascular benefits. 1, 2
• The combination of empagliflozin and a GLP-1 receptor agonist is reasonable and may provide additive non-glycemic benefits (blood pressure, weight), though not specifically studied for cardiovascular outcomes. 1

Key Contraindications to Verify

Confirm this is type 2 diabetes, not type 1 or autoimmune diabetes, as empagliflozin is contraindicated in insulinopenic diabetes due to severe diabetic ketoacidosis risk. 8

• SGLT2 inhibitors are FDA-approved exclusively for type 2 diabetes. 8
• In type 1 or autoimmune diabetes, the combination of insulin deficiency and SGLT2 inhibitor-induced ketogenesis creates dangerous metabolic conditions. 8