Reduce Insulin Glargine (Lantus) First
In a patient with improved glycemic control on empagliflozin, metformin, and insulin glargine, you should reduce the insulin glargine dose first, as insulin carries the highest risk of hypoglycemia and weight gain, while both empagliflozin and metformin provide cardiovascular and metabolic benefits that should be preserved. 1
Rationale for Insulin Reduction
Insulin poses the greatest safety risk in the context of improved glycemic control, with significant potential for hypoglycemia and associated weight gain, making it the priority medication for de-intensification 1
Empagliflozin should be maintained because SGLT2 inhibitors provide documented cardiovascular and renal benefits that persist independent of glucose-lowering effects, and these benefits are preserved even as GFR declines 2
Metformin should be continued as it remains first-line therapy for type 2 diabetes with proven safety, cardiovascular neutrality, and can be used safely with eGFR ≥30 mL/min/1.73 m² 1, 2
Specific Insulin Reduction Protocol
Follow this stepwise approach for insulin de-intensification:
Reduce insulin glargine dose by 10-30% every few days while monitoring fasting glucose values, targeting fasting glucose of 90-150 mg/dL (5.0-8.3 mmol/L) 1
Monitor fasting finger-stick glucose over one week to guide dose adjustments: if >50% of values exceed goal, increase by 2 units; if >2 values/week are <80 mg/dL (<4.4 mmol/L), decrease by 2 units 1
Taper insulin over 2-6 weeks if glucose targets are consistently met, with the goal of potentially discontinuing insulin entirely if glycemic control remains adequate on empagliflozin and metformin alone 1
Change timing from bedtime to morning if simplification is needed, as this reduces nocturnal hypoglycemia risk while maintaining glycemic control 1
Why Not Reduce Metformin or Empagliflozin
Metformin preservation is critical because:
It provides foundational glucose control with minimal hypoglycemia risk and should only be discontinued if contraindicated by renal function (eGFR <30 mL/min/1.73 m²) or intolerance 1, 2
The combination of empagliflozin and metformin has demonstrated superior HbA1c reduction (-1.9 to -2.1%) compared to either agent alone, with significant weight loss benefits (-2.8 to -3.8 kg) 3
Empagliflozin preservation is essential because:
SGLT2 inhibitors provide cardiovascular mortality reduction and heart failure hospitalization benefits that extend beyond glucose lowering, making them a priority medication to maintain 2
The glucose-lowering efficacy may be reduced as GFR declines, but kidney and cardiovascular benefits are preserved regardless of glycemic control 2
Empagliflozin added to metformin therapy resulted in 16.1% decrease in HbA1c and 23.8% decrease in fasting blood sugar without exacerbating toxicity 4
Monitoring During Insulin Reduction
Check fasting glucose daily during the initial 1-2 weeks of insulin dose reduction to ensure glucose values remain within target range 1
Reassess HbA1c within 3 months after completing insulin de-intensification to confirm maintained glycemic control 1
Monitor for hyperglycemia symptoms (polyuria, polydipsia, weight loss) that would indicate inadequate glucose control requiring insulin dose stabilization 1
Critical Safety Considerations
Do not reduce insulin if HbA1c is >7.5% or if the patient has symptomatic hyperglycemia, as this indicates inadequate overall glucose control requiring continued or intensified therapy 1
Avoid simultaneous reduction of multiple medications, as this makes it impossible to determine which agent is providing glycemic benefit and increases risk of hyperglycemic excursions 1
Educate patients on genital mycotic infection risk (6% incidence) with empagliflozin, which is higher in women, and withhold during prolonged fasting, surgery, or critical illness due to ketoacidosis risk 2