What is the rate of insulin dose reduction in an adult patient with type 2 diabetes mellitus (T2DM) after adding a Sodium-Glucose Cotransporter 2 (SGLT2) inhibitor, such as empagliflozin (Jardiance) or canagliflozin (Invokana), to their existing insulin therapy regimen?

Insulin Dose Reduction After Adding SGLT2 Inhibitors

Direct Answer

Reduce total daily insulin dose by approximately 20% when initiating an SGLT2 inhibitor in patients with type 2 diabetes to minimize hypoglycemia risk. 1

Evidence-Based Insulin Reduction Strategy

Initial Dose Adjustment at SGLT2 Inhibitor Initiation

• The American College of Cardiology recommends reducing total daily insulin dose by 20% at the time of SGLT2 inhibitor initiation to reduce hypoglycemia risk, particularly in patients on complex insulin regimens. 1

• Avoid substantial initial insulin reductions greater than 20%, as this may increase the risk of diabetic ketoacidosis according to the American College of Cardiology. 1

• Patients on complex insulin regimens or with history of labile blood glucose should have SGLT2 inhibitors initiated in collaboration with their diabetes care provider. 1

Long-Term Insulin Requirement Reductions

In the EMPA-REG OUTCOME trial, empagliflozin demonstrated remarkable sustained effects on insulin requirements over a median 3.1-year follow-up: 2

• Among insulin-naïve patients (52% of participants), empagliflozin reduced new insulin initiation by 60% (7.1% vs. 16.4% with placebo; HR 0.40 [95% CI 0.32-0.49]; P < .0001). 2

• Among patients already using insulin at baseline (48% of participants), empagliflozin reduced the need for >20% insulin dose increases by 58% (14.4% vs. 29.3% with placebo; HR 0.42 [95% CI 0.36-0.49]; P < .0001). 2

• Empagliflozin increased the proportion achieving sustained >20% insulin dose reductions without subsequent HbA1c increases compared with placebo (9.2% vs. 4.9%; HR 1.87 [95% CI 1.39-2.51]; P < .0001). 2

• Sensitivity analyses confirmed consistent findings when insulin dose changes of >10% or >30% were considered. 2

Clinical Monitoring Protocol

First 3-4 Weeks After Initiation

• Close blood glucose monitoring is essential during the first 3-4 weeks after initiating SGLT2 inhibitors, especially in patients on insulin, as recommended by the American College of Cardiology. 1

• Patients should be advised to self-monitor blood glucose levels closely during this initial period. 1

Hypoglycemia Risk Management

• Patients taking insulin should be advised of the risk of hypoglycemic events when adding SGLT2 inhibitors for cardiovascular benefit. 1

• The risk of hypoglycemia is not significantly increased with the addition of SGLT2 inhibitors in patients who are not taking either insulin or an insulin secretagogue. 1

• SGLT2 inhibitors have no intrinsic risk of hypoglycemia when used alone or with metformin, due to their insulin-independent mechanism of action. 3, 4

Critical Safety Considerations

Euglycemic Diabetic Ketoacidosis Prevention

• Patients should be informed about the unlikely but serious risk of euglycemic diabetic ketoacidosis and advised to seek immediate care if they develop symptoms (nausea, vomiting, abdominal pain, generalized weakness). 1

• Substantial initial reductions in insulin dose (>20%) should be avoided after initiation of SGLT2 inhibitors to prevent ketoacidosis risk. 1

• Approximately 5-10% of adult-onset diabetes is late-onset type 1; these patients have an increased risk of diabetic ketoacidosis. 1

Insulin Secretagogue Adjustments

• In patients taking sulfonylureas or glinides, consider reducing the dose by 50% to at most 50% of the maximum recommended dose, or discontinuing these agents if already on a minimal dose. 1

• Complex insulin regimens or "brittle" diabetes should be carefully managed in coordination with the patient's diabetes care provider. 1

Common Pitfalls to Avoid

• Do not reduce insulin by more than 20% initially, as this increases diabetic ketoacidosis risk while providing no additional benefit. 1

• Do not assume that all patients will require the same degree of insulin reduction—those on lower baseline insulin doses or with better glycemic control may require more conservative reductions. 1

• Do not discontinue close monitoring after the first week—the full 3-4 week period is critical for identifying patterns and making appropriate adjustments. 1

• Do not forget to educate patients about maintaining at least low-dose insulin during sick days even when SGLT2 inhibitors are held, as complete insulin cessation increases DKA risk. 1