What is the effect of Jardiance (Empagliflozin) on blood sugar control in patients with type 2 diabetes taking Humalog 75-25 (Insulin Lispro Protamine/Insulin Lispro)?

Effect of Jardiance on Blood Sugar Control in Patients Taking Humalog 75-25

Jardiance (empagliflozin) will provide additional blood glucose reduction when added to Humalog 75-25, but you must reduce the insulin dose by approximately 20% at initiation to prevent hypoglycemia, and the glucose-lowering effect will be modest (HbA1c reduction of 0.5-0.7%) compared to the substantial cardiovascular and renal benefits. 1

Mechanism and Expected Glycemic Effect

• Empagliflozin works through an insulin-independent mechanism by promoting urinary glucose excretion (up to 90g daily), which complements rather than duplicates the action of insulin 2, 3
• When added to insulin therapy, empagliflozin provides significant HbA1c improvements while simultaneously allowing insulin dose reductions 3
• The glucose-lowering effect is dose-dependent, with 10 mg daily (the recommended starting dose) providing meaningful but not dramatic glycemic improvement 1, 2

Critical Insulin Dose Adjustment Required

• If the patient's HbA1c is well-controlled at baseline or if there is a history of frequent hypoglycemic events, reduce the total daily insulin dose by approximately 20% when starting empagliflozin 1
• This dose reduction applies to both the rapid-acting (lispro) and intermediate-acting (protamine lispro) components of Humalog 75-25 1
• Monitor blood glucose closely during the first few weeks, checking at least 4-6 times daily to identify patterns and guide further insulin adjustments 4

Renal Function Determines Glucose-Lowering Efficacy

• Empagliflozin's glucose-lowering effect declines substantially when eGFR falls below 45 mL/min/1.73 m² 1, 5
• Do not initiate empagliflozin for glycemic control if eGFR is <45 mL/min/1.73 m², though it can be continued for cardiovascular and renal benefits down to eGFR 20 mL/min/1.73 m² 1
• The cardiovascular and renal protective effects persist even when glucose-lowering efficacy diminishes 1, 2

Beyond Glucose: The Primary Benefits

• The most compelling reason to add empagliflozin to insulin therapy is not primarily for glucose control, but for cardiovascular death reduction (38% relative risk reduction) and heart failure hospitalization reduction (35% relative risk reduction) in patients with established cardiovascular disease 1, 2, 5
• Empagliflozin provides renoprotective effects independent of glycemic control, slowing eGFR decline and reducing albuminuria 1
• Additional benefits include modest weight loss (typically 2-3 kg) and systolic blood pressure reduction (3-5 mmHg), both favorable in insulin-treated patients who often experience weight gain 2, 3

Hypoglycemia Risk Management

• Empagliflozin alone carries a low inherent risk of hypoglycemia due to its insulin-independent mechanism 2, 3
• However, when combined with insulin, the hypoglycemia risk increases significantly unless insulin doses are proactively reduced 1, 6
• Teach patients the 15-15 rule: administer 15-20g of rapid-acting glucose and recheck after 15 minutes if hypoglycemia occurs 6
• Intensify glucose monitoring to every 4-6 hours initially, particularly before meals and at bedtime 4

Specific Adverse Events to Monitor

• Genital mycotic infections occur more frequently with empagliflozin (typically straightforward to manage with topical antifungals) but urinary tract infections are not significantly increased 2, 7
• There is a slight increase in ketoacidosis risk, though absolute rates remain low; educate patients to stop empagliflozin and seek immediate care if they develop dyspnea, nausea, vomiting, or abdominal pain 1, 7
• Serious volume depletion may occur, particularly in elderly patients or those on diuretics; consider reducing diuretic doses when initiating empagliflozin 1, 7
• Unlike canagliflozin, empagliflozin has not been associated with increased risk of amputations or bone fractures 1, 2

Dosing and Titration Strategy

• Start empagliflozin at 10 mg orally once daily, which is the dose tested in cardiovascular outcomes trials 1
• No further dose titration is needed for cardiovascular or renal risk reduction, though increasing to 25 mg daily may provide additional glucose reduction if eGFR remains ≥45 mL/min/1.73 m² 1
• Reassess HbA1c within 3 months; if glycemic targets are not met, further adjust insulin doses rather than immediately increasing empagliflozin 1

Common Pitfalls to Avoid

• Do not fail to reduce insulin doses proactively—waiting for hypoglycemia to occur before adjusting is dangerous, particularly in elderly patients 1, 4
• Do not discontinue empagliflozin at least 3 days before planned surgery to prevent postoperative ketoacidosis 1
• Do not use empagliflozin as the primary strategy for intensive glucose lowering in patients with severe hyperglycemia (glucose >200 mg/dL); insulin intensification is more appropriate in this scenario 1
• Monitor serum potassium if the patient is also taking ACE inhibitors, ARBs, or diuretics, as these combinations can cause electrolyte disturbances 1

Patient Education Essentials

• Explain that empagliflozin works by causing the kidneys to excrete excess glucose in urine, which is why adequate hydration is important 2, 3
• Emphasize that the medication provides heart and kidney protection beyond glucose control, which is particularly valuable for patients with established cardiovascular disease 1, 2
• Teach patients to increase glucose monitoring during illness or if symptoms of hyperglycemia or hypoglycemia develop 6
• Instruct patients that genital hygiene is important to minimize infection risk 7