International Journal of Obesity (London), 2012;36(6):843-854
[DOI] [PubMed] [Google Scholar] 4.Honigberg M.C., Chang L.S., McGuire D.K., Plutzky J., Aroda V.R., Vaduganathan M
First, dose-escalation with 4-week intervals at each step is the validated approach jumping directly to target dose is not how the clinical data was generated
Therefore, the SGLT2-i induced elevated ANG II levels could act through AT2R resulting in vasodilation, sodium excretion, antiproliferative and anti-inflammation effects ( In addition, it has also been observed a SGLT2-i induced ACE2/ANG(1-7) pathway activation that may play a role in cardioprotection by competing with ANG II and AT1R ( Furthermore, the SGLT2-i hybrid diuretic effect, which combines natriuresis and osmotic diuresis, might also have cardioprotective properties leading to preload and myocardial stretch reduction (the diuretic hypothesis) ( Therefore, SGLT2-i diuretic properties show a major advantage compared to thiazides and thiazides-like diuretics, which act on the Na + CL - -cotransporter in the distal convoluted tubule, or loop diuretics, which block the Na-K-2Cl co-transporter of both the Henle loop and the macula densa, making the macula insensitive to the increased tubular sodium coming from the Henle loop
