Osmotic diuretics are known to increase the urinary excretion of most electrolytes.65 In studies with dapagliflozin, there were no biologically appropriate decreases in serum electrolytes in rats or dogs at supratherapeutic doses. In both rats and dogs, there have been increases inside the urinary excretion of calcium and phosphorus . Standard mice taken care of with ten mg/kg of dapagliflozin greater sodium excretion . Increases in urinary sodium excretion were also observed in 1-month studies in rats and canines but not in longer duration research, this kind of as the 6-month rat and 12-month puppy toxicity research, as a consequence of a presumed compensatory response. Human research Similarly, in human research, there was a transient grow in urinary sodium excretion.66 No changes have been observed in imply serum sodium, calcium, or potassium levels.43,45,48,67 A tiny imply enhance in serum magnesium was seen during the 5 mg groups with the monotherapy study.43 Very similar little imply increases had been observed in other clinical studies and therefore are deemed not possible for being of clinical rel?evance.
48,58 Like other mild diuretics, 10 mg dapagliflozin is associated across dig this all research to date with imply reductions in systolic and diastolic blood pressure, despite the fact that this result remains to become confirmed in studies controlling for concomitant antihy?pertensives.43,45,47,48,58,67 Orthostatic hypotension was hardly ever observed, whilst it has been reported inside a healthy, normotensive subject in combination with a loop diuretic, bumetanide.68 Moreover, tiny imply increases in hematocrit and hemoglobin were observed while in the initially twelve?16 weeks just after starting up dapagliflozin, with minimum increases thereafter; this was not associated with an increase in thromboembolic events.
43,45,47,48,58,67 Renal security Animal versions Because of the renal mechanism of dapagliflozin, the kidney status/function was cautiously evaluated in dapagliflozin-treated animals. Dapagliflozin administered for 2 weeks to rats with early streptozotocin-induced diabetes had no result on kidney size discover this or GFR.69 Supratherapeutic doses in rats with exposures up to 675 instances human exposures at the expected greatest advisable dose showed no renal toxicity . Histopathologic alterations of rat renal tubular mineralization, minimum necrosis/regeneration, and an exacerbation of persistent progressive nephropathy weren’t observed till quite high exposure multiples inside a 6-month examine with each day dosing of dapagliflozin. Additionally, no renal histopathologic findings had been observed in dogs despite exposure multiples .3000-fold.
Mild proteinuria linked with all the diuretic impact of dapagliflozin was observed in rats for exposures 85-fold better than the human exposures on the greatest recommended dose. Administration of diuretics in rats has previously been related with enhanced urinary protein70 and N-acetyl-?-D-glucosaminidase excretion71 inside the absence of renal toxicity.