Jardiance A1C Reduction in Type 2 Diabetes
Jardiance (empagliflozin) lowers A1C by approximately 0.5% to 0.8% in patients with type 2 diabetes, with the magnitude of reduction depending on baseline glycemic control and renal function. 1, 2
Expected A1C Reduction by Clinical Context
Monotherapy or Add-on to Metformin:
- In patients with baseline A1C of 7.8-8.2%, empagliflozin 10 mg reduces A1C by approximately 0.7% and empagliflozin 25 mg by 0.77% compared to placebo after 24 weeks 3
- The Chinese Diabetes Guidelines report SGLT2 inhibitors reduce A1C by approximately 0.5% to 1.0% 1
- The American Diabetes Association states each SGLT2 inhibitor added to metformin generally lowers A1C by approximately 0.7-1.0% 2
Combination with Other Agents:
- When added to pioglitazone with or without metformin, empagliflozin 10 mg reduces A1C by 0.6% and 25 mg by 0.7% versus placebo 4
- When added to insulin therapy, empagliflozin 10 mg reduces A1C by 0.6% and 25 mg by 0.7% at 18 weeks 4
- In multiple daily injection insulin regimens (>60 IU/day), empagliflozin 10 mg reduces A1C by 0.9% and 25 mg by 1.0% versus placebo 4
Impact of Renal Function on Efficacy
The glucose-lowering effect of empagliflozin decreases substantially with declining renal function 4:
- eGFR 60 to <90 mL/min/1.73 m²: A1C reduction of -0.6%
- eGFR 45 to <60 mL/min/1.73 m²: A1C reduction of -0.5%
- eGFR 30 to <45 mL/min/1.73 m²: A1C reduction of -0.2%
Do not use empagliflozin for glycemic control when eGFR <45 mL/min/1.73 m² 1. However, empagliflozin should still be initiated or continued for cardiovascular and renal protection down to eGFR ≥25 mL/min/1.73 m² in patients with established cardiovascular disease or diabetic nephropathy with albuminuria 5.
Dose Comparison
Both 10 mg and 25 mg doses provide similar A1C reductions 4, 3:
- The 10 mg dose is the recommended starting dose for cardiovascular risk reduction 1
- The 25 mg dose may provide marginally greater A1C reduction (approximately 0.1% more) but does not offer additional cardiovascular benefit 4
- No dose titration beyond 10 mg is necessary for cardiovascular risk reduction 2
Clinical Positioning for Glycemic Control
GLP-1 receptor agonists are positioned above SGLT2 inhibitors in treatment hierarchies due to greater glycemic potency 1, 2. The glucose-lowering effect of empagliflozin is considered moderate compared to GLP-1 receptor agonists 2. Many patients will require combination therapy with both a GLP-1 receptor agonist and SGLT2 inhibitor plus metformin to achieve glycemic goals 1, 2.
Important Caveats
When adding empagliflozin to patients already on insulin or sulfonylureas, reduce the insulin dose by approximately 20% or wean/stop the sulfonylurea to prevent hypoglycemia 1, 5. This is particularly critical in patients with well-controlled baseline A1C or history of frequent hypoglycemic events 1.
The cardiovascular and renal benefits of empagliflozin are independent of its glucose-lowering effect 1, 6. The mortality reduction observed in EMPA-REG OUTCOME (38% reduction in cardiovascular death) occurred within months and appears related to prevention of heart failure rather than glycemic control 6. Therefore, empagliflozin should be prescribed to patients with type 2 diabetes and established cardiovascular disease regardless of baseline A1C level 1, 5.