In an uncontrolled self‑pay adult with type 2 diabetes on Synjardy (metformin/empagliflozin) and eGFR ≥ 45 mL/min/1.73 m², can I initiate basal insulin while continuing Synjardy?

Initiating Basal Insulin While Continuing Synjardy in an Uncontrolled Self‑Pay Patient with Type 2 Diabetes

Yes, you should initiate basal insulin while continuing Synjardy (metformin/empagliflozin), provided the patient's eGFR is ≥ 30 mL/min/1.73 m² for metformin safety and ≥ 20–25 mL/min/1.73 m² for empagliflozin's cardiorenal protection.

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Step 1: Confirm Renal Function Before Proceeding

• Measure eGFR within the past 4 weeks to determine whether both components of Synjardy can be safely continued. 1
• If eGFR ≥ 45 mL/min/1.73 m², continue Synjardy at the current dose without adjustment; both metformin and empagliflozin retain full efficacy. 2, 3
• If eGFR is 30–44 mL/min/1.73 m², reduce metformin to a maximum of 1000 mg daily and continue empagliflozin 10 or 25 mg once daily for cardiorenal protection (glucose‑lowering effect will be diminished but cardiovascular and renal benefits persist). 3, 1
• If eGFR is 20–29 mL/min/1.73 m², discontinue metformin immediately but continue empagliflozin for cardiorenal protection; initiate basal insulin as the primary glucose‑lowering agent. 3, 1
• If eGFR < 20 mL/min/1.73 m², discontinue both metformin and empagliflozin; use insulin as monotherapy. 3, 1

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Step 2: Initiate Basal Insulin with Dose Adjustment to Prevent Hypoglycemia

• Start basal insulin (NPH, glargine U‑100, detemir, or degludec) at 10 units once daily in the morning rather than at bedtime, which simplifies the regimen and reduces nocturnal hypoglycemia risk in older adults. 4
• Reduce the total daily insulin dose by 20–25 % if baseline HbA1c is < 8.5 % to mitigate hypoglycemia risk when adding empagliflozin, which lowers glucose independently of insulin. 4, 2
• Titrate basal insulin by 2 units every 3–7 days based on fasting glucose values; target fasting glucose of 90–150 mg/dL (5.0–8.3 mmol/L) in older adults or those with multiple comorbidities. 4
• If ≥ 50 % of fasting glucose readings exceed the target over one week, increase the basal dose by 2 units; if > 2 fasting readings per week are < 80 mg/dL (< 4.4 mmol/L), decrease by 2 units. 4

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Step 3: Continue Synjardy for Cardiorenal Protection

• Do not discontinue empagliflozin when initiating insulin, as SGLT2 inhibitors reduce cardiovascular death or heart‑failure hospitalization by 26–29 %, slow kidney disease progression by 39–44 %, and lower all‑cause mortality by 31 % in patients with eGFR ≥ 20–25 mL/min/1.73 m². 2, 3
• Empagliflozin's glucose‑lowering efficacy declines when eGFR < 45 mL/min/1.73 m², but its cardiorenal benefits remain robust; therefore, continue the drug for organ protection even if glycemic control is primarily achieved with insulin. 2, 3
• Metformin should be continued at the appropriate renal dose (maximum 1000 mg daily for eGFR 30–44 mL/min/1.73 m²) because population studies show reduced mortality compared with other glucose‑lowering agents in this eGFR range. 1

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Step 4: Monitor Closely for Hypoglycemia and Volume Depletion

• Check fasting glucose daily for the first 2–4 weeks after starting insulin to guide dose titration and detect hypoglycemia early. 4
• Assess volume status before and after insulin initiation, especially in patients on loop or thiazide diuretics, as empagliflozin causes mild osmotic diuresis; consider reducing diuretic doses if signs of volume depletion appear. 4, 2
• Re‑measure eGFR 1–2 weeks after starting insulin (or after any acute illness) to detect transient declines; an expected hemodynamic dip of 2–5 mL/min/1.73 m² may occur with empagliflozin and should not prompt discontinuation. 4, 2
• Monitor for genital mycotic infections (≈ 6 % incidence with SGLT2 inhibitors vs. 1 % with placebo) and counsel on daily hygiene to reduce risk. 2

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Step 5: Educate the Patient on Sick‑Day Rules

• Instruct the patient to withhold empagliflozin during acute illness with reduced oral intake, fever, vomiting, or diarrhea to prevent euglycemic diabetic ketoacidosis and volume depletion. 4, 2
• Maintain at least a low‑dose basal insulin regimen even when empagliflozin is held, as complete insulin cessation increases ketoacidosis risk. 2
• Warn about euglycemic diabetic ketoacidosis (can occur with normal blood glucose) and advise immediate medical evaluation for unexplained malaise, nausea, vomiting, or abdominal pain. 4, 2
• Hold empagliflozin at least 3 days before major surgery or procedures requiring prolonged fasting to prevent postoperative ketoacidosis. 4, 2

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Step 6: Simplify the Insulin Regimen if Self‑Management Is Limited

• If the patient struggles with daily insulin titration or multiple injections, use a simplified basal‑only regimen (one injection in the morning) rather than adding prandial insulin. 4
• Avoid rapid‑ or short‑acting insulin at bedtime to reduce nocturnal hypoglycemia risk. 4
• If premeal glucose values remain > 250 mg/dL (> 13.9 mmol/L) despite basal insulin, give 2 units of short‑ or rapid‑acting insulin before meals; if > 350 mg/dL (> 19.4 mmol/L), give 4 units. 4
• Discontinue sliding‑scale insulin when it is no longer needed daily, as prolonged use increases complexity without improving outcomes. 4

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Step 7: Address Cost Barriers for the Self‑Pay Patient

• Empagliflozin (Synjardy component) has no generic equivalent in the United States; explore manufacturer patient‑assistance programs (e.g., Boehringer Ingelheim's patient support) to reduce out‑of‑pocket costs. 3
• If Synjardy is unaffordable, substitute with separate tablets: metformin extended‑release 1000 mg once daily plus empagliflozin 10 or 25 mg once daily, or switch to dapagliflozin 10 mg once daily (which has similar cardiorenal benefits and may have different formulary coverage). 3
• NPH insulin is the least expensive basal insulin option and can be used once daily in the morning for self‑pay patients; glargine U‑100 biosimilars (e.g., Basaglar, Semglee) are also cost‑effective alternatives. 4
• If insulin cost is prohibitive, prioritize continuing the SGLT2 inhibitor (empagliflozin or dapagliflozin) for cardiorenal protection and accept a higher HbA1c target (e.g., 8.0–8.5 %) to avoid the expense of intensive insulin therapy. 4, 3

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Common Pitfalls to Avoid

• Do not discontinue empagliflozin when eGFR falls below 45 mL/min/1.73 m²; cardiorenal benefits persist despite reduced glycemic efficacy. 2, 3
• Do not stop empagliflozin in response to the expected early eGFR dip (2–5 mL/min/1.73 m² within 2–4 weeks); this change is hemodynamic and reversible. 4, 2
• Do not reduce the empagliflozin dose below the standard 10 or 25 mg for cardiovascular or renal indications, even at lower eGFR levels; all outcome trials used fixed doses. 2, 3
• Do not combine empagliflozin with a sulfonylurea when starting insulin, as this triple combination markedly increases hypoglycemia risk without additional cardiovascular benefit; if the patient is on a sulfonylurea, discontinue it when insulin is initiated. 4, 3
• Do not use creatinine alone to guide metformin dosing; always calculate eGFR, especially in elderly or low‑body‑weight patients, to avoid inappropriate discontinuation. 1

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Alternative Strategy if Insulin Initiation Is Deferred

• If the patient declines insulin or cannot afford it, add a GLP‑1 receptor agonist (e.g., semaglutide, dulaglutide, liraglutide) to Synjardy for additional glucose lowering, cardiovascular protection, and weight loss without hypoglycemia risk. 3
• GLP‑1 receptor agonists require no renal dose adjustment and can be used safely when eGFR > 15–30 mL/min/1.73 m² (agent‑specific). 3
• Tirzepatide (dual GIP/GLP‑1 agonist) provides the greatest HbA1c reduction (≈ 1.9–2.6 %) and weight loss (≈ 6–13 kg) but is more expensive; initiate at 2.5 mg subcutaneously weekly and titrate to 5–10 mg at 4‑week intervals. 3