What is the cause of increasing Hemoglobin A1c (HbA1c) on Jardiance (Empagliflozin) alone?

From the Guidelines

The increasing Hemoglobin A1c (HbA1c) on Jardiance (Empagliflozin) alone is likely due to various factors, including inadequate dose, poor adherence, or presence of comorbidities, and not a direct result of the medication itself, as evidenced by a recent multicenter double-blind, placebo-controlled trial showing a significant reduction in A1C of 0.84% with empagliflozin compared to placebo 1.

Possible Causes of Increasing HbA1c

• Inadequate dose: The standard starting dose of Jardiance is 10 mg once daily, and it may need to be increased to 25 mg once daily for optimal efficacy.
• Poor adherence: Patients may not be taking the medication as prescribed, leading to inadequate glucose control.
• Presence of comorbidities: Certain conditions, such as chronic kidney disease, iron deficiency anemia, or hemolytic anemia, can affect HbA1c measurement and lead to falsely elevated or lowered levels 1.
• Racial/ethnic differences: HbA1c levels can vary among different racial and ethnic groups, with African Americans tend to have higher HbA1c values than white persons for a given level of glycemia 1.

Recommendations

• Regular monitoring of kidney function and HbA1c levels to adjust the dose of Jardiance as needed.
• Patient education on the importance of adherence to the medication regimen and lifestyle modifications, such as diet and exercise.
• Consideration of comorbidities and racial/ethnic differences when interpreting HbA1c results.
• Potential addition of other glucose-lowering agents or lifestyle interventions to achieve optimal glucose control.

Mechanism of Action

Jardiance works by blocking glucose reabsorption in the kidneys, causing excess glucose to be excreted in urine, which lowers blood sugar levels. This mechanism is independent of insulin, making it effective even when there is insulin resistance or decreased insulin production. In addition to A1C reduction, Jardiance offers cardiovascular benefits and potential weight loss of 2-3 kg, as shown in the EMPA-REG trial 1.

From the Research

Causes of Increasing Hemoglobin A1c (HbA1c) on Jardiance (Empagliflozin) Alone

• The provided studies do not directly address the cause of increasing Hemoglobin A1c (HbA1c) on Jardiance (Empagliflozin) alone 2, 3, 4, 5, 6.
• However, it can be inferred that the efficacy of empagliflozin in reducing HbA1c levels may decrease over time or in certain patient populations, such as those with renal insufficiency 4.
• Additionally, the studies suggest that empagliflozin may have a moderate glucose-lowering effect, with an average reduction in HbA1c of around 0.5-0.8% compared to placebo 2, 3, 4.
• It is also possible that the increase in HbA1c levels may be due to other factors, such as changes in diet, physical activity, or other medications, rather than a decrease in the efficacy of empagliflozin itself.

Patient Factors That May Influence HbA1c Levels on Empagliflozin

• Renal insufficiency: The efficacy of empagliflozin in reducing HbA1c levels may be decreased in patients with renal insufficiency 4.
• Cardiovascular risk factors: Empagliflozin has been shown to have cardiovascular benefits, particularly in patients with a history of cardiovascular disease 2.
• Diabetes type: Empagliflozin has been studied in patients with type 2 diabetes, but its efficacy and safety in patients with type 1 diabetes are also being investigated 5.

Study Limitations

• The provided studies have varying durations, patient populations, and study designs, which may limit the generalizability of the findings 2, 3, 4, 5, 6.
• Further research is needed to fully understand the causes of increasing HbA1c levels on Jardiance (Empagliflozin) alone and to identify patient factors that may influence treatment efficacy.