A1C Reduction with Jardiance (Empagliflozin)
Jardiance reduces A1C by approximately 0.7-0.8% when used as monotherapy and 0.5-0.9% when added to other diabetes medications in patients with type 2 diabetes. 1, 2
Magnitude of A1C Reduction by Clinical Context
Monotherapy
- In treatment-naïve patients with baseline A1C of 7.9%, empagliflozin 10 mg reduced A1C by 0.7% and empagliflozin 25 mg reduced A1C by 0.8% compared to placebo at 24 weeks 2
- These reductions are consistent with the general expectation that non-insulin agents lower A1C by approximately 0.7-1.0% when added to metformin 1
Add-On Combination Therapy
- When added to metformin in patients with baseline A1C around 8%, empagliflozin demonstrated similar A1C reductions of 0.5-0.9% 2, 3
- In combination with pioglitazone (with or without metformin) over 76 weeks, empagliflozin 10 mg reduced A1C by 0.59% and empagliflozin 25 mg by 0.69% compared to placebo 4
- In youth aged 10-17 years with type 2 diabetes, empagliflozin reduced A1C by 0.84% compared to placebo 1
Baseline A1C Impact on Efficacy
- At baseline A1C below 8.5%, empagliflozin produces an additive effect when combined with other agents 5
- At baseline A1C above 8.5%, the A1C reduction is less than additive compared to monotherapy effects 5
- This means patients with higher baseline A1C values may need more aggressive combination therapy from the outset 6
Durability of Glycemic Effect
- The A1C reduction with empagliflozin is sustained over time, with maintained efficacy demonstrated through 76 weeks of treatment 4
- The glucose-lowering effect is considered moderate compared to other antidiabetic classes, particularly GLP-1 receptor agonists 6, 3
Important Caveats Affecting A1C Reduction
Renal Function Limitation
- Empagliflozin should not be used for glycemic control when eGFR <45 mL/min/1.73 m² due to decreased efficacy 1
- An even smaller A1C reduction occurs in patients with renal impairment 3
- The mechanism depends on adequate glomerular filtration to produce glucosuria 5
Dose Considerations
- The 25 mg dose provides marginally greater A1C reduction than the 10 mg dose (approximately 0.1% additional reduction) 2, 4
- For cardiovascular risk reduction, no dose titration beyond 10 mg is necessary, as cardiovascular benefits are achieved at this dose 1
Clinical Positioning
- While empagliflozin has proven cardiovascular and renal benefits in patients with established cardiovascular disease, its glucose-lowering potency is moderate 6, 3
- GLP-1 receptor agonists are positioned above SGLT2 inhibitors in treatment hierarchies due to greater glycemic potency, though both classes offer cardiovascular benefits 6
- Many patients will require combination therapy with GLP-1 receptor agonists, SGLT2 inhibitors, and metformin to achieve glycemic goals 6