From the Guidelines
Yes, SGLT2 inhibitors like dapagliflozin (Farxiga) can cause metabolic acidosis, specifically a form called euglycemic diabetic ketoacidosis (euDKA), as reported in the most recent study 1.
Key Points to Consider
- SGLT2 inhibitors work by preventing glucose reabsorption in the kidneys, leading to increased urinary glucose excretion, which can trigger increased ketone production and reduced ketone clearance, resulting in ketoacidosis even when blood glucose levels are not severely elevated (hence "euglycemic") 1.
- Risk factors for euDKA include reduced carbohydrate intake, alcohol consumption, surgery, acute illness, reduced insulin doses, and dehydration 1.
- Symptoms of euDKA include nausea, vomiting, abdominal pain, fatigue, and rapid breathing, and if suspected, patients should stop the medication, check ketones if possible, and seek immediate medical attention 1.
- Blood tests typically show low bicarbonate, elevated anion gap, and the presence of ketones, and treatment involves IV fluids, insulin, and glucose as needed to resolve the acidosis 1.
Recommendations for Patients and Healthcare Providers
- Patients with type 2 diabetes requiring insulin are at particular risk of euDKA, and to mitigate this risk, it is essential to maintain at least low-dose insulin and consider pausing SGLT2i treatment during periods of acute illness or stressors 1.
- Blood or urine ketone monitoring may be used for ketosis detection, and patients with signs, symptoms, or biochemical evidence of ketoacidosis should discontinue SGLT2i therapy and seek immediate medical attention 1.
- Daily hygienic measures may lessen the risk of genital mycotic infections, a known complication of SGLT2i, and most genital mycotic infections are easily treated, but severe cases of Fournier gangrene have been reported 1.
From the FDA Drug Label
In patients with type 1 diabetes mellitus, dapagliflozin significantly increases the risk of diabetic ketoacidosis, a life-threatening event, beyond the background rate In placebo-controlled trials of patients with type 1 diabetes mellitus, the risk of ketoacidosis was markedly increased in patients who received sodium-glucose cotransporter 2 (SGLT2) inhibitors compared to patients who received placebo. Type 2 diabetes mellitus and pancreatic disorders (e.g., history of pancreatitis or pancreatic surgery) are also risk factors for ketoacidosis. There have been postmarketing reports of fatal events of ketoacidosis in patients with type 2 diabetes mellitus using SGLT2 inhibitors, including dapagliflozin Precipitating conditions for diabetic ketoacidosis or other ketoacidosis include under-insulinization due to insulin dose reduction or missed insulin doses, acute febrile illness, reduced caloric intake, ketogenic diet, surgery, volume depletion, and alcohol abuse Signs and symptoms are consistent with dehydration and severe metabolic acidosis and include nausea, vomiting, abdominal pain, generalized malaise, and shortness of breath. Blood glucose levels at presentation may be below those typically expected for diabetic ketoacidosis (e.g., less than 250 mg/dL). Ketoacidosis and glucosuria may persist longer than typically expected. Urinary glucose excretion persists for 3 days after discontinuing DAPAGLIFLOZIN TABLETS [see Clinical Pharmacology (12. 2)]; however, there have been postmarketing reports of ketoacidosis and/or glucosuria lasting greater than 6 days and some up to 2 weeks after discontinuation of SGLT2 inhibitors.
Yes, SGLT2 inhibitors, including dapagliflozin and canagliflozin, can cause metabolic acidosis, specifically diabetic ketoacidosis, in patients with type 1 and type 2 diabetes mellitus.
- Risk factors for ketoacidosis include type 1 diabetes mellitus, type 2 diabetes mellitus, pancreatic disorders, under-insulinization, acute febrile illness, reduced caloric intake, ketogenic diet, surgery, volume depletion, and alcohol abuse.
- Signs and symptoms of ketoacidosis include nausea, vomiting, abdominal pain, generalized malaise, and shortness of breath, and may be associated with dehydration and severe metabolic acidosis.
- Ketoacidosis may persist longer than typically expected, and urinary glucose excretion may persist for several days after discontinuing SGLT2 inhibitors 2, 3, 3.
From the Research
Metabolic Acidosis and SGLT2 Inhibitors
- SGLT2 inhibitors, such as canagliflozin, dapagliflozin, and empagliflozin, have been associated with an increased risk of metabolic acidosis, including diabetic ketoacidosis (DKA) and euglycemic DKA 4, 5, 6.
- The risk of metabolic acidosis is higher when SGLT2 inhibitors are used in combination with metformin, as both drugs can increase the risk of lactic acidosis and DKA 4.
- Farxiga (dapagliflozin) is an SGLT2 inhibitor that has been shown to be effective in improving glycemic control, but it may also increase the risk of metabolic acidosis, particularly when used in patients with renal impairment or those who are taking other medications that increase the risk of acidosis 7.
Guardian and Metabolic Acidosis
- There is no direct evidence in the provided studies that links Guardian to an increased risk of metabolic acidosis.
- However, it is possible that Guardian may interact with other medications, such as SGLT2 inhibitors, to increase the risk of metabolic acidosis.
SGLT2 Inhibitors and Metabolic Acidosis
- SGLT2 inhibitors work by reducing glucose reabsorption in the kidneys, which can lead to an increase in glucose excretion in the urine 8, 6.
- This mechanism of action can also increase the risk of metabolic acidosis, particularly in patients with renal impairment or those who are taking other medications that increase the risk of acidosis 4, 5.
- The risk of metabolic acidosis associated with SGLT2 inhibitors can be mitigated by monitoring patients for signs and symptoms of acidosis, such as nausea, vomiting, and abdominal pain, and by adjusting the dose or discontinuing the medication if necessary 5, 8.