From the Guidelines
Yes, there is a threshold blood glucose level below which dapagliflozin will not cause significant glucose excretion in the urine, approximately 70-90 mg/dL (3.9-5.0 mmol/L), as indicated by the renal threshold for glucose reabsorption 1. Dapagliflozin works by inhibiting sodium-glucose cotransporter-2 (SGLT2) in the proximal tubule of the kidney, which normally reabsorbs about 90% of filtered glucose. When blood glucose levels fall below this threshold, there is minimal filtered glucose for the medication to affect, so glucosuria (glucose excretion in urine) becomes negligible. This mechanism provides some protection against severe hypoglycemia with dapagliflozin, unlike insulin or sulfonylureas which can continue to lower blood glucose regardless of the starting level. However, patients should still be cautious about hypoglycemia risk, especially when dapagliflozin is used in combination with other glucose-lowering medications. Regular blood glucose monitoring is recommended, particularly when initiating therapy or adjusting doses. Some key points to consider include:
- The primary outcome of the DAPA-CKD trial showed a hazard ratio of 0.70 for the composite outcome of end-stage renal disease, doubling of creatinine, or death from renal or cardiovascular cause 1.
- The EMPEROR-Reduced trial demonstrated a hazard ratio of 0.89 for the key secondary outcome of all-cause and cardiovascular mortality 1.
- The CANVAS program showed a hazard ratio of 0.93 for the primary outcome of major adverse cardiovascular events 1. It is essential to consider these findings in the context of individual patient care, taking into account factors such as renal function, cardiovascular risk, and concomitant medications. By prioritizing the most recent and highest-quality study, we can provide the best possible guidance for patient management, focusing on minimizing morbidity, mortality, and optimizing quality of life 1.
From the Research
Dapagliflozin Mechanism of Action
- Dapagliflozin works by inhibiting the sodium-glucose co-transporter-2 (SGLT2) in the kidneys, reducing renal glucose reabsorption and leading to urinary glucose excretion and a reduction in blood glucose levels 2, 3.
- This mechanism of action is independent of insulin secretion and action, making dapagliflozin a unique and complementary therapy for the management of type 2 diabetes 2, 4.
Threshold Blood Glucose Level
- There is no specific mention of a threshold blood glucose level below which dapagliflozin will not cause the kidney to excrete glucose in the provided studies.
- However, dapagliflozin has been shown to increase urinary glucose excretion and reduce plasma glucose levels in clinical trials, with improvements in glycaemic control and a low risk of hypoglycaemia 2, 3, 4.
Clinical Trials and Safety
- Dapagliflozin has been studied in several clinical trials, including phase III randomized, double-blind trials, and has been shown to be effective in reducing HbA1c and fasting plasma glucose levels compared to placebo 2, 3.
- Common side effects of dapagliflozin include infections of the urogenital system, and there is a potential increased risk of cancer, although this is still unclear and not statistically significant 5.
- Dapagliflozin has a favorable safety profile, with a low propensity to cause hypoglycaemia, especially when used alone or in combination with metformin 2, 3.