From the Guidelines
The presence of glycosuria in a diabetic patient taking Sodium-Glucose Linked Transporter inhibitors (SGLT inhibitors) is likely due to the medication's mechanism of action, which deliberately causes glucosuria by blocking glucose reabsorption in the kidneys, and not necessarily a sign of poor glycemic control. SGLT inhibitors like empagliflozin, canagliflozin, and dapagliflozin work by promoting urinary glucose excretion, which is the intended therapeutic effect of these medications to lower blood glucose 1. The glucosuria caused by SGLT inhibitors can be significant, with a 4+ reading on a urine dipstick, even when blood glucose levels are well-controlled.
Key Points to Consider
- SGLT inhibitors make urine glucose testing unreliable for monitoring glycemic control, and instead, blood glucose monitoring or HbA1c should be used to assess diabetes management in these patients 1.
- Patients should be reassured that glycosuria is a normal finding while on SGLT inhibitors and does not necessarily indicate worsening diabetes.
- However, if the patient is experiencing symptoms of hyperglycemia (excessive thirst, frequent urination, fatigue) despite this medication, blood glucose levels should be checked to rule out true hyperglycemia requiring treatment adjustment.
- Other potential causes of glycosuria in patients taking SGLT inhibitors, such as diabetic ketoacidosis, should be considered, particularly in patients with type 1 diabetes or a history of ketoacidosis 1.
- Clinicians should assess the underlying susceptibility to diabetic ketoacidosis, provide education regarding the risks, symptoms, and prevention strategies, and prescribe home monitoring supplies for b-hydroxybutyrate to minimize the risk of ketoacidosis in patients taking SGLT inhibitors 1.
From the FDA Drug Label
Positive Urine Glucose Test Clinical Impact:SGLT2 inhibitors increase urinary glucose excretion which will lead to positive urine glucose tests. The possible cause of glycosuria in a diabetic patient taking Sodium-Glucose Linked Transporter inhibitors (SGLT inhibitors) is the increased urinary glucose excretion caused by the SGLT2 inhibitors themselves 2.
- Key points:
- SGLT2 inhibitors increase urinary glucose excretion
- This will lead to positive urine glucose tests
- Monitoring glycemic control with urine glucose tests is not recommended in patients taking SGLT2 inhibitors 2
From the Research
Possible Causes of Glycosuria in Diabetic Patients Taking SGLT Inhibitors
The possible causes of glycosuria in diabetic patients taking Sodium-Glucose Linked Transporter inhibitors (SGLT inhibitors) include:
- Increased urinary excretion of excess glucose due to the inhibition of renal reabsorption of glucose by SGLT2 inhibitors 3, 4, 5
- Novel insulin-independent mechanism of SGLT2 inhibitors, which promotes glucosuria and results in a reduction in fasting and postprandial glycaemia 4
- Blockage of glucose reabsorption in the proximal convoluted tubules, resulting in markedly increased glycosuria 5
Factors Influencing Glycosuria in Diabetic Patients Taking SGLT Inhibitors
Factors that may influence glycosuria in diabetic patients taking SGLT inhibitors include:
- Degree of insulin resistance or beta-cell dysfunction, which does not limit the mechanism of SGLT2 inhibitors 5
- Renal function, as SGLT2 inhibitors are less effective in patients with renal insufficiency and should be stopped if estimated glomerular filtration rate is below 45 ml/min/1.73 m2 4
- Concomitant use of other antihyperglycemic agents, which may increase the risk of hypoglycemia 4, 6
Adverse Effects Related to Glycosuria in Diabetic Patients Taking SGLT Inhibitors
Adverse effects related to glycosuria in diabetic patients taking SGLT inhibitors include:
- Genital infections and urinary tract infections, which are more frequent in patients treated with SGLT2 inhibitors compared to those receiving placebo 3, 4
- Euglycemic diabetic ketoacidosis (DKA), which has been associated with SGLT2 inhibitors, particularly in patients with type 2 diabetes 6
- Hyperglycemic, high anion-gap metabolic acidosis, which has been reported in patients receiving SGLT-2 inhibitors for diabetes management 6