Yes, you can safely start Jardiance 25 mg daily and metformin 1000 mg SA daily without significant concern for hypoglycemia in this patient with A1c 11.7% who refuses insulin.
Hypoglycemia Risk Assessment
The combination of empagliflozin (Jardiance) and metformin carries minimal hypoglycemia risk because neither medication directly stimulates insulin secretion. 1, 2
- Metformin works by reducing hepatic glucose production and improving insulin sensitivity—it does not cause hypoglycemia when used alone 3
- Empagliflozin (SGLT-2 inhibitor) works by increasing urinary glucose excretion independent of insulin, resulting in extremely low hypoglycemia rates 1, 4
- In clinical trials of empagliflozin 25 mg added to metformin, documented symptomatic hypoglycemia occurred in only 1.6-3.8% of patients, with no episodes requiring assistance 1, 4, 5
Appropriateness of This Regimen for Severe Hyperglycemia
While this combination is safe from a hypoglycemia standpoint, you should counsel the patient that with an A1c of 11.7%, insulin therapy would be the most effective treatment and this refusal may delay optimal glycemic control. 3
- Guidelines recommend considering insulin for patients with marked hyperglycemia (A1C ≥8.5%) from the outset 3, 6
- However, when insulin is refused, initiating dual therapy with metformin plus an SGLT-2 inhibitor is a reasonable alternative that can achieve meaningful A1c reductions 1, 4, 5
Expected Efficacy
This combination should reduce A1c by approximately 1.5-2.1% over 24 weeks:
- Empagliflozin 25 mg added to metformin reduces A1c by 0.6-0.8% 1
- When started as initial combination therapy in treatment-naïve patients with baseline A1c 8.6-8.9%, empagliflozin 25 mg + metformin 2000 mg reduced A1c by 2.1% 1, 5
- This would bring your patient's A1c from 11.7% to approximately 9.6-10.2%—still above target but a meaningful improvement 1, 5
Dosing Considerations
Start metformin at a lower dose and titrate upward to minimize gastrointestinal side effects:
- Begin with metformin 500 mg daily with the largest meal, then increase by 500 mg weekly as tolerated up to 1000 mg twice daily (2000 mg total) 6
- Empagliflozin 25 mg can be started immediately at full dose as it does not require titration 1
- Check renal function (eGFR) before starting—metformin requires eGFR ≥30 mL/min/1.73 m² and empagliflozin is most effective with eGFR ≥45 mL/min/1.73 m² 6, 1
Critical Monitoring and Follow-Up
Reassess A1c in 3 months and prepare to intensify therapy if target is not approached:
- Monitor for volume depletion and genital mycotic infections (common with SGLT-2 inhibitors) 1
- Check vitamin B12 levels annually on long-term metformin therapy 6
- If A1c remains >9% after 3-6 months on this regimen, strongly reconsider insulin therapy or add a GLP-1 receptor agonist 3, 7
Common Pitfalls to Avoid
- Do not add a sulfonylurea to this regimen—it would introduce significant hypoglycemia risk and cause weight gain 2
- Do not delay treatment intensification beyond 3-6 months if glycemic targets are not approached—therapeutic inertia at this level of hyperglycemia increases complication risk 7
- Ensure the patient understands this is a compromise approach and that insulin remains the gold standard for severe hyperglycemia 3