How many calories do SGLT2 inhibitors make you pee out?

Like just peeing out 30 units of glucose is not that many calories given how few carbs you need to pump up a diabetic’s glucose levels by that much (but then the cells might release more intracellular glucose into the bloodstream if they sense low glucose?)

I thought Peter Attia mentioned in passing that it was a few hundred cal per day, although it would be highly dependent on carb quantity ingested and I believe glycemic index as well.

How long do they last in the blood/how long do they act for?

You really should install the epocrates app. Canagliflozin has half-life of 10-13 hours, so it reaches a steady state with repeated once daily dosing and works 24/7.

By lowering your Glucose using SGLT2 inhibitors or others you are lowering the inflammation in your body which is main contributor to plaque build up throughout the body. High glucose also packs on the fat which is unhealthy and contributes to insultin resistence. To lower weigh, you can use Metformin which lowers glucose levels in Liver, Acarbose which works immediately in the gut, SGLT2 inhibitors which sends a good % of glucose into your urine. I have taken all 3 and my appetite is also decreased thus have lost 10 kg. weight. Currently 71", 165 lbs.


Are some of the SGLT2 inhibitors more effective than the others?

Also at what dose is the effect highest? Like, I’m taking 100mg canagliflozin - don’t some people take 300mg and is the effect higher at 300mg?

I’ve tried cana 100mg and empagliflozin 12.5 as well as 25. If you look at the studies in the package insert (full prescribing info) there are really diminishing returns from the higher doses vs lower dose. It seems a waste of money to take the higher dose except possibly for a raging diabetic who is doing everything he can to get every point of glucose down. That’s my take on it, anyway.


Is it roughly 75% of the rate at 150mg vs 300mg?
" Urinary glucose excretion persists for 3 days after discontinuing INVOKANA"
oh i totally noticed this


To reiterate, renal tubule SGLT-2 is the main site of action of canagliflozin, but in the time frame shortly after dosing, when canagliflozin is in the gut lumen and thus has direct access to the site of inhibition of SGLT-1. This site of action (SGLT-1) may be responsible for the observed suppression of postprandial increase in plasma glucose. Canagliflozin’s package label recommends taking before the first meal of the day. The above-disclosed scenario regarding gut SGLT-1 was used to justify this recommendation. Regarding the observed suppression by canagliflozin of postprandial glucose, FDA’s Medical Review stated that, “Canagliflozen 300 mg given before a meal reduced the postprandial glucose excursion, which was not seen with 150 dose. This may be due to increased SGLT-1 inhibition in the intestinal lumen with the higher dose, before the drug gets absorbed.”90

Commenting further on canagliflozin’s inhibition of gut SGLT-1, FDA’s ClinPharm Review stated, “It is speculated that after dosing, and during drug absorption, canagliflozin levels within the lumen … could transiently be high enough to inhibit gastrointestinal SGLT-1-mediated glucose absorption and thereby reduce prandial plasma glucose excursions. Sponsor conducted a study … to investigate the effect of canagliflozin (300 mg) on gastrointestinal glucose absorption … in healthy subjects using a dual-tracer method … [w]ith canagliflozin, the rate of systemic appearance of orally ingested radioactive-glucose (a measure of intestinal glucose absorption) was lower for the first 90 minutes compared to placebo.”91

In a study of healthy subjects (N=24), Devineni et al (2014) 2 evaluated the effect of food on the PK of canagliflozin 300 mg tablets in an open-label, randomized, single-dose, 2-period crossover trial.

  • Subjects were randomized (1:1) to receive either canagliflozin 300 mg once daily on days 1–4 under fasted condition in Period-1, followed by a 10-14-day washout, and then canagliflozin 300 mg once daily on days 1–4 under fed condition in Period-2, or vice versa. The absence of a food effect was to be concluded if limits of the 90% CIs for the ratios of geometric mean ratios (GMRs) for AUC and Cmax were between 80% and 125%.
  • All subjects fasted for at least 10 hours overnight. For fed state, subjects were provided with a standardized high-fat breakfast 30 minutes prior to dosing.
  • Twenty-two subjects were under the fed state and 21 under the fasting state.
  • Mean plasma concentration-time profiles of canagliflozin were similar under fasted and fed conditions. Mean plasma concentration increased rapidly with a median tmax of 2 hours under both fed and fasting conditions; and mean t1/2 was 12.9 hours under fasting conditions and 12.6 hours under fed conditions.
  • After canagliflozin administration, the GMRs of canagliflozin under the fed condition relative to the fasted condition for AUC∞, AUClast, and Cmax were 108.09% (90% CI: 103.45, 112.95), 108.34% (90% CI: 103.77, 113.11), and 100.51% (90% CI: 89.47, 112.93), respectively. The 90% CIs for the GMRs between fed and fasting conditions were within the bioequivalence limits of 80–125% for AUC and Cmax
  • Treatment emergent adverse events were more frequent under fasting conditions (36.4%; n=8/24) as compared to fed conditions (13.0%; n=3/24).


Sha et al (2011) 3 conducted a double-blind, randomized, placebo-controlled, ascending-dose phase 1 study evaluating the safety, tolerability and pharmacodynamics (PD) of canagliflozin in healthy men (N=63) randomized to receive canagliflozin (n=48) or placebo (n=15).

  • Canagliflozin (10, 30, 100, 200, 400, 600 or 800 mg once daily or 400 mg twice daily) was administered to 8 cohorts (6 subjects/cohort: Canagliflozin; 2 subjects/cohort: placebo). Each subject received only one dose of study medication.
  • Three standardized meals were provided at 30 minutes, 4.5 hours (h) and 10.5 h after the day 1 morning dose (for the 400 mg twice daily cohort, the evening meal was given at 30 minutes after the evening dose).
  • At canagliflozin doses >200 mg administered 30 minutes before breakfast, a reduction in the rate of PPG absorption was observed over the first 2 hours as compared with canagliflozin 100 mg or 200 mg.
  • This effect of canagliflozin doses >200 mg on PPG over the first 2 hours was subsequently confirmed by other Phase 1 studies4,5 that administered the dose 20 minutes before breakfast. Polidori et al (2013) 4 reported that canagliflozin 300 mg slowed the rate of PPG absorption over the first 2 hours as compared to placebo in healthy subjects. Stein et al (2014) 5 reported that canagliflozin 300 mg slowed the rate of PPG absorption over the first 2 hours as compared to canagliflozin 150 mg and placebo in patients with T2DM.

Polidori et al (2013) 4 showed in a randomized, double-blind, placebo-controlled, two-period crossover study that in healthy male subjects, a single 300-mg dose of canagliflozin administered before a 600-kcal meal reduced PPG excursions (N=20).

  • Subjects were randomized to either canagliflozin 300 mg in treatment period 1, followed by matching placebo in period 2, or vice versa, with a washout period of 7–21 days between treatment periods.
  • Mean PPG ΔAUC values were ~44%, 35%, and 26% lower during the 0- to 1-hour, 0- to 2-hours, and 0- to 6-hours postmeal intervals, respectively, after administration of canagliflozin 300 mg compared to placebo.
  • Treatment with canagliflozin reduced the amount of oral glucose absorption (AUC RaO) compared with placebo by 31% over the 0- to 1-hour interval (P=0.001) and by 20% over the 0- to 2-h interval (P=0.01). This was followed by a 34% increase in AUC RaO in the 2- to 6-hour interval for canagliflozin 300 mg compared with placebo. The AUC RaO over 0- to 6-hours was only ~6% lower for canagliflozin compared with placebo (P=0.003).
  • Postprandial plasma insulin ΔAUC were 43%, 43%, and 33% lower during the 0- to 1-hour, 0- to 2-hours, and 0- to 6-hours after meal intervals, respectively, for canagliflozin compared to placebo.


what dose results in 180pp, canagliflozin?

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