What are the considerations for using Jardiance (Empagliflozin) with insulin in a patient with type 2 diabetes and adequate kidney function?

Using Jardiance (Empagliflozin) with Insulin in Type 2 Diabetes

When adding Jardiance to insulin therapy in patients with type 2 diabetes and adequate kidney function (eGFR ≥20 mL/min/1.73 m²), reduce the total daily insulin dose by approximately 20% at initiation to minimize hypoglycemia risk, while maintaining the SGLT2 inhibitor for its cardiovascular and renal protective benefits. 1

Initial Insulin Dose Adjustment Algorithm

When initiating Jardiance in patients already on insulin:

• If HbA1c is well-controlled at baseline (<7.5%) or the patient has a history of frequent hypoglycemic events: Reduce total daily insulin dose by up to 20% when starting Jardiance 1
• If HbA1c is poorly controlled (>8%): Consider a more modest insulin reduction of 10-15% or no reduction, with close monitoring 1
• If basal insulin dose exceeds 0.5 units/kg/day: This signals potential overbasalization; reassess the entire insulin regimen and consider more aggressive dose reduction when adding Jardiance 1

Monitoring Requirements During the First 4 Weeks

Instruct patients to monitor glucose more closely at home for the first 4 weeks of combined therapy, particularly focusing on: 1

• Fasting glucose levels (to guide basal insulin adjustments)
• Pre-meal glucose readings (to guide prandial insulin if applicable)
• Any episodes of hypoglycemia, even if mild

Reassess therapy within 3 months to determine if further insulin titration is needed or if glycemic targets have been achieved 1

Critical Safety Education Points

Diabetic Ketoacidosis (DKA) Risk

Educate patients that DKA can occur even with blood glucose readings in the 150-250 mg/dL range (euglycemic DKA), which is particularly concerning in insulin-requiring patients. 1 Patients should:

• Recognize DKA symptoms: nausea, vomiting, abdominal pain, weakness 1
• Seek urgent medical attention if these symptoms develop 1
• Maintain at least low-dose insulin therapy and consider pausing Jardiance during acute illness, surgery, or periods of poor oral intake 1

Volume Depletion and Hypotension

• Avoid hypovolemia by educating patients about dehydration symptoms: lightheadedness, orthostasis, weakness 1
• Consider reducing diuretic dose if the patient has symptoms of dehydration 1
• Instruct patients to hold Jardiance if experiencing low oral intake 1

Genital Mycotic Infections

• Educate patients regarding genital hygiene and the potential for genital mycotic infections (occurring in approximately 6% of patients on SGLT2 inhibitors vs. 1% on placebo) 1
• Most infections are easily treated, but severe cases (Fournier gangrene) have been reported 1

Foot Care

• Educate patients regarding foot care, especially those with diabetic neuropathy 1
• Instruct patients to report any foot wounds immediately 1
• While canagliflozin has been associated with increased amputation risk, empagliflozin has not shown this association 1, 2

Renal Function Considerations

Jardiance can be initiated if eGFR is ≥20 mL/min/1.73 m² and continued even as eGFR declines below this threshold. 1

• At eGFR 30-44 mL/min/1.73 m²: Glucose-lowering efficacy is reduced, but cardiovascular and renal benefits persist 1
• At eGFR <30 mL/min/1.73 m²: Initiation is not recommended for glycemic control, but may be continued for heart failure benefits if already established 1
• Monitor eGFR every 3-6 months when eGFR is <60 mL/min/1.73 m² 1

Cardiovascular and Renal Benefits Independent of Glycemic Control

The primary rationale for combining Jardiance with insulin extends beyond glucose lowering to include proven cardiovascular and renal protection. 1, 2

• Empagliflozin reduced cardiovascular death by 38% and heart failure hospitalization by 35% in the EMPA-REG OUTCOME trial 2, 3
• Empagliflozin reduced incident or worsening nephropathy by 39% and doubling of serum creatinine by 44% 4
• These benefits occur through mechanisms independent of glycemic control, including diuretic effects, blood pressure reduction (2-4 mmHg systolic), and direct cardioprotective effects 4, 2, 3

When to Avoid or Use with Extreme Caution

Do not use Jardiance in patients with: 1

• History of diabetic ketoacidosis
• Active severe illness, vomiting, or dehydration
• Planned surgery or procedures requiring fasting
• History of recurrent genital candidiasis (relative contraindication)

Use clinical judgment when initiating Jardiance in patients who are starting or up-titrating an ACE inhibitor or ARB if renal function is impaired, as the combination may transiently affect kidney function. 1

Common Pitfalls to Avoid

1. Failing to reduce insulin dose at initiation: This is the most common error leading to hypoglycemia in the first weeks of therapy 1
2. Discontinuing Jardiance when glucose control improves: The cardiovascular and renal benefits are the primary indication, not just glucose lowering 1
3. Missing euglycemic DKA: Always consider DKA even with glucose <250 mg/dL in patients on SGLT2 inhibitors with insulin 1, 5
4. Not educating about sick-day management: Patients must know to hold Jardiance during acute illness while maintaining insulin 1