From the Guidelines
The most likely cause of ketoacidosis in a patient on Metformin, Jardiance (Empagliflozin), and Saxagliptin is the Jardiance, an SGLT2 inhibitor, which has a known risk of causing euglycemic diabetic ketoacidosis (euDKA) as warned by the FDA in 2015 1.
Key Points to Consider
- SGLT2 inhibitors like Jardiance increase glucagon levels and reduce insulin, creating a hormonal environment that promotes ketone production even when blood glucose isn't severely elevated.
- Saxagliptin, a DPP-4 inhibitor, rarely causes ketoacidosis on its own but may not provide enough protection against it when combined with an SGLT2 inhibitor.
- Metformin typically doesn't cause ketoacidosis and may actually help prevent it.
- Risk factors that could exacerbate ketoacidosis with this medication combination include acute illness, surgery, reduced food intake, excessive alcohol consumption, dehydration, or insulin dose reduction.
Management and Prevention
- If ketoacidosis is suspected, the SGLT2 inhibitor (Jardiance) should be temporarily discontinued, fluids and insulin administered, and the underlying trigger addressed.
- Patients on this combination should be educated about ketoacidosis symptoms including nausea, vomiting, abdominal pain, fatigue, and difficulty breathing, and advised to seek immediate medical attention if these develop.
- According to a 2019 study, SGLT-2 inhibitors like Empagliflozin have been associated with ketoacidosis, and their use requires careful consideration of the patient's risk factors and close monitoring for signs of ketoacidosis 1.
Conclusion Not Applicable - Direct Answer Only
In summary, Jardiance (Empagliflozin) is the most likely cause of ketoacidosis in this patient, and its use should be carefully monitored and managed to prevent this potentially life-threatening condition, as supported by the most recent evidence from 2019 1.
From the FDA Drug Label
5 WARNINGS AND PRECAUTIONS
- 1 Ketoacidosis Reports of ketoacidosis, a serious life-threatening condition requiring urgent hospitalization have been identified in clinical trials and postmarketing surveillance in patients with type 1 and type 2 diabetes mellitus receiving sodium glucose co-transporter-2 (SGLT2) inhibitors, including JARDIANCE. ... Before initiating JARDIANCE, consider factors in the patient history that may predispose to ketoacidosis including pancreatic insulin deficiency from any cause, caloric restriction, and alcohol abuse
The cause of ketoacidosis in a patient on Metformin, Jardiance (Empagliflozin), and Saxagliptin may be related to the use of JARDIANCE, an SGLT2 inhibitor, which has been associated with an increased risk of ketoacidosis. Key factors that may predispose to ketoacidosis include:
- Pancreatic insulin deficiency from any cause
- Caloric restriction
- Alcohol abuse It is essential to consider these factors in the patient's history and educate patients on the signs and symptoms of ketoacidosis 2.
From the Research
Cause of Ketoacidosis
The cause of ketoacidosis in a patient on Metformin, Jardiance (Empagliflozin), and Saxagliptin can be attributed to the use of SGLT2 inhibitors, such as Empagliflozin.
- SGLT2 inhibitors increase the risk of ketoacidosis, even in patients with type 2 diabetes, by reducing renal tubular glucose reabsorption and increasing urinary glucose excretion 3, 4, 5, 6.
- This can lead to a state of euglycemic diabetic ketoacidosis, where the patient presents with ketoacidosis despite having normal or only mildly elevated blood glucose levels 3, 4, 5, 6.
- The exact mechanism is not fully understood, but it is thought to be related to the increased glucose excretion in the urine, which can lead to a state of relative insulin deficiency and increased ketone production 4.
- Other factors, such as acute illness, decreased carbohydrate intake, or discontinuation of insulin, can also contribute to the development of ketoacidosis in patients taking SGLT2 inhibitors 5.
Risk Factors
Patients taking SGLT2 inhibitors, such as Empagliflozin, are at risk for ketoacidosis, particularly if they have:
- Type 2 diabetes 3, 4, 5, 6
- Acute illness or infection 5, 7
- Decreased carbohydrate intake or fasting 5
- Discontinuation of insulin or other diabetes medications 5
- History of ketoacidosis or diabetic ketoacidosis 7
Clinical Presentation
Patients with ketoacidosis may present with: