There really is not enough information about dosing of SGLT2i. I’ll take the example of empagliflozin. I have looked for papers that have addressed the effects of a standard 10mg/day dose vs 25mg/dose, and honestly there are not many that clearly focus on this, which is pretty astonishing. There is a trial underway that looks at this very difference (10mg vs 25mg), but it won’t be completed for a while.
The standard recommendation is to take the dose in the morning. Studies have shown that there are no real differences between taking a dose in the morning vs evening.
As we know, a lot of medication protocol and dosing recommendations by pharma companies and physicians is driven not by what is optimally best from a physiological point of view, but what is more likely to produce superior compliance from the patient. And so, a weekly injection will be recommended, even though a daily smaller dose might be more efficatious, or a single large dose daily instead of smaller two doses daily.
This is where my question enters. I am currently taking empagliflozin approx. 12.5mg/day (25mg pill split in two), and have noted some positive effect on morning fasting glucose levels (generally holding them below 100, whereas before it was routinely 105-115).
As I start my rapamycin intervention, there may be an effect of blood glucose rise, but more importantly, I am interested in lowering my A1c. In view of that, I foresee the possibility that the 12.5mg/day will not accomplish that, as apparently SGLT2i (empagliflozin) is most effective in lowering A1c if it’s well above 6 to begin with. But mine is in the prediabetic range of 5.7-5.9, so I suspect it may not do that.
In any case, I anticipate the possibility that one option would be moving to the 25mg/day dose. It is my understanding, that like with statins, the majority of the effect is found at the lower dose and you are not buying that much, proportionally with the higher dose.
However, at least in part, perhaps, depending on the drug, it may be a function of dosing schedules. Perhaps you will get a better effect by instead of taking one 25mg dose, split the dose in two, 12.5mg and take one in the morning and one in the evening, roughly 12 hours apart. Whether this will work depends on the mechanism. The SGLT2 inhibits a protein. What is the function of a dose here - more of the empa agent binds to more of the protein and thus achieves more of an effect, or does more of the empa agent last longer and therefore achieve more of an effect through time until the next dose. I tend to think the former, because an empa dose lasts for more than 24 hours when attenuating, so if that’s true for both 10mg and 25mg, then it stands to reason that the higher dose simply binds more of the protein. If so, then splitting the 25mg dose into two 12.5mg taken twice a day is not going to be better than simply taking a single 25mg dose.
Thoughts? Has anyone experimented with the dosing protocol of SGLT2i? TIA!
