ADR BULLETEIN

ADR BULLETEIN

BY SHINU.C,ASST  PROFESSOR,DEPT OF PHARMACY PRACTICE,ACP

SGLT2 inhibitors for Diabetes may result in a serious condition of too much acid in the blood

SGLT2 inhibitors (sodium-glucose cotransporter-2) are a class of prescription medicines that are FDA-approved for use with diet and exercise to lower blood sugar in adults with type 2 diabetes. When untreated, type 2 diabetes can lead to serious problems, including blindness, nerve and kidney damage, and heart disease. SGLT2 inhibitors lower blood sugar by causing the kidneys to remove sugar from the body through the urine. These medicines are available as single-ingredient products and also in combination with other diabetes medicines such as metformin. The safety and efficacy of SGLT2 inhibitors have not been established in patients with type1 diabetes, and FDA has not approved them for use in these patients.

 SGLT2 inhibitors like canagliflozin, dapagliflozin, and empagliflozin may lead to ketoacidosis, a serious condition where the body produces high levels of blood acids called ketones that may require hospitalization. In addition to acidosis, other possible side effects of SGLT2 inhibitors include dehydration, kidney problems, low blood sugar when this class of medicines is combined with other prescription medicines used to treat diabetes, increased cholesterol in the blood, and yeast infections.

Patients should pay close attention for any signs of ketoacidosis and seek medical attention immediately if they experience symptoms such as difficulty breathing, nausea, vomiting, abdominal pain, confusion, and unusual fatigue or sleepiness. Do not stop or change your diabetes medicines without first talking to your prescriber. Health care professionals should evaluate for the presence of acidosis, including ketoacidosis, in patients experiencing these signs or symptoms; discontinue SGLT2 inhibitors if acidosis is confirmed; and take appropriate measures to correct the acidosis and monitor sugar levels.

One year study revealed 20 cases of acidosis reported as diabetic ketoacidosis (DKA), ketoacidosis, or ketosis in patients treated with SGLT2 inhibitors. All patients required emergency room visits or hospitalization to treat the ketoacidosis.

DKA, a subset of ketoacidosis or ketosis in diabetic patients, is a type of acidosis that usually develops when insulin levels are too low or during prolonged fasting. DKA most commonly occurs in patients with type 1 diabetes and is usually accompanied by high blood sugar levels. The FAERS cases were not typical for DKA because most of the patients had type 2 diabetes and their blood sugar levels, when reported, were only slightly increased compared to typical cases of DKA. Factors identified in some reports as having potentially triggered the ketoacidosis included major illness, reduced food and fluid intake, and reduced insulin dose.

Additional information for patient:

·         Acidosis is when there is too much acid in the body. Diabetic ketoacidosis and ketoacidosis, serious conditions in which the body produces high levels of blood acids called ketones, have been reported in patients using the diabetes medicines known as sodium-glucose cotransporter-2 (SGLT2) inhibitors . Ketones can build up in the body if insulin levels are too low or during prolonged fasting.

·         Pay close attention for any signs or symptoms of acidosis such as difficulty breathing, nausea, vomiting, abdominal pain, confusion, and unusual fatigue or sleepiness. Seek medical attention immediately if you experience any of these symptoms.

·         Ketoacidosis associated with SGLT2 inhibitors may be present even if the blood sugar is not very high.

·         The safety and efficacy of SGLT2 inhibitors have not been established in patients with type 1 diabetes, and FDA has not approved them for use in these patients.

·         Do not stop or change your diabetes medicines without first talking to your health care professional. When untreated, diabetes can lead to serious problems, including blindness, nerve and kidney damage, and heart disease.

·         Talk to your health care professional if you have questions or concerns about SGLT2 inhibitors or any of your other diabetes medicines.

·         Report side effects from SGLT2 inhibitors.

Additional information for health care professionals:

·         Evaluate for the presence of acidosis, including ketoacidosis, in patients experiencing signs or symptoms of acidosis; discontinue SGLT2 inhibitors if acidosis is confirmed; and take appropriate measures to correct the acidosis and to monitor glucose levels.

·         Supportive medical care should be instituted to treat and correct factors that may have precipitated or contributed to the metabolic acidosis.

·         Inform patients and caregivers of the signs and symptoms of metabolic acidosis, such as tachypnea or hyperventilation, anorexia, abdominal pain, nausea, vomiting, lethargy, or mental status changes, and instruct them to seek medical attention immediately if they experience the signs or symptoms.

·         SGLT2 inhibitors are not FDA-approved to treat patients with type 1 diabetes mellitus.

·         The high anion gap metabolic acidosis accompanied by elevation in urine or serum ketones in the reported cases was not associated with the very high glucose levels that are typical for diabetic ketoacidosis.

·         Potential diabetic ketoacidosis (DKA) triggering factors identified in some cases included acute illness (e.g., urinary tract infection, urosepsis, gastroenteritis, influenza, or trauma), reduced caloric or fluid intake, and reduced insulin dose.

·         Potential factors contributing to the high anion gap metabolic acidosis identified in some cases included hypovolemia, acute renal failure, hypoxemia, reduced oral intake, and a history of alcohol use.

·         In all cases, the patients required emergency room visits or hospitalization to treat the acidosis.

·         Report adverse events involving SGLT2 inhibitors.