Anyone have any experience with using the SGLT2 inhibitor, Fargixa? If so, good or bad results? And what dosage?
I’ve only tried canaglozin and empagliflozin, and for me empagliflozin works well.
You can do a search on google for a comparison of depagliflozin, empagliflozin and canagliflozin.
These comparisons seem to be focused on efficacy in their primary clinical indications - diabetes-related blood glucose management and heart disease - but perhaps a good guideline generally.
1 Like
Thank you. Great information.
It seems Kachhela is a company that is only about 6 years old. Personally, I trust the larger Indian Pharma that have been around for many decades more than the new, small startup Pharma companies… the bigger ones likely have better quality control systems in place:
https://www.thecompanycheck.com/company/kachhela-medex-private-limited/U52100MH2015PTC271064
I just got my dapagliflozin in the mail today!
| eGFR (mL/min/1.73 m2) | 55.6±24.2 | 49.9±22.4 | <0.001 | 0.621 |
|---|---|---|---|---|
| Canagliflozin (n=34) | 55.8±22.5 | 50.7±22.6 | <0.001 | |
| Dapagliflozin (n=24) | 51.5±24.6 | 46.5±23.1 | 0.003 | |
| Empagliflozin (n=23) | 59.4±26.4 | 52.3±21.9 | <0.001 |
Why this decrease?
Because the 3 agents differ in the selectivity of SGLT1/SGLT2 and the duration of action,18 the effect of SGLT2i on HF is possibly different. Of the 3 agents, the selectivity of SGLT1/SGLT2 for canagliflozin is relatively low, while the selectivity for empagliflozin is relatively high, and the selectivity for dapagliflozin is intermediate. The selectivity of SGLT1/SGLT2 for ipragliflozin is also relatively low. Urine sugar excretion and urine volume are increased in both SGLT2 and SGLT1 knockout mice compared with SGLT2 alone knockout mice.19 If the selectivity of SGLT1/SGLT2 inhibition is relatively lower, the fluid reduction effect might be stronger, which might result in a further decrease in BNP. Contrary to such an expectation, however, no clear differences were found between the 3 SGLT2i. This suggests that the differences in SGLT1/SGLT2 selectivity with regard to HF benefit may not be so important between these 3 SGLT2i.
SGLT2i with a longer-acting duration might result in a longer diuretic action via the increase of urinary sugar and urine volume. While dapagliflozin and ipragliflozin are long-acting, canagliflozin and empagliflozin are considered to have an intermediate duration of action
Aims
To compare the pharmacodynamic effects of the highest approved doses of the sodium glucose co‐transporter 2 (SGLT2) inhibitors canagliflozin and dapagliflozin on urinary glucose excretion (UGE), renal threshold for glucose excretion (RTG) and postprandial plasma glucose (PPG) excursion in healthy participants in a randomized, double‐blind, two‐period crossover study.
Methods
In each treatment period, participants (n = 54) received canagliflozin 300 mg or dapagliflozin 10 mg for 4 days (20 min before breakfast). A mixed‐meal tolerance test (600 kcal; 75 g glucose) was performed at baseline and on day 4 of each treatment period to assess changes in incremental PPG (PPGΔAUC 0–2 h). We measured 24‐h UGE and plasma glucose on day 4 to determine 24‐h mean RTG.
Results
Canagliflozin 300 mg and dapagliflozin 10 mg had similar effects on UGE and RTG for 4 h after dosing, but canagliflozin was associated with higher UGE and greater RTG reductions for the remainder of the day. Mean 24‐h UGE was ∼25% higher with canagliflozin than with dapagliflozin (51.4 vs. 40.8 g), and 24‐h mean RTG was ∼0.4 mmol/l (7 mg/dl) lower with canagliflozin than with dapagliflozin (3.79 vs. 4.17 mmol/l; p < 0.0001). Dapagliflozin had no effect on PPG excursion; canagliflozin delayed and reduced PPG excursion (between‐treatment difference in PPGΔAUC 0–2 h from baseline expressed as a percentage of baseline mean, −10.2%; p = 0.0122). Canagliflozin and dapagliflozin were generally well tolerated.
It has been estimated that the highest approved therapeutic dose of dapagliflozin (10 mg) increases 24‐h UGE in healthy individuals to ∼70% of the maximum UGE observed at higher dapagliflozin doses of 20–100 mg 8. By contrast, 24‐h UGE values reported in studies of canagliflozin in healthy participants indicate that canagliflozin provides near‐maximal effects on UGE at doses >200 mg 4; however, the lack of direct comparison limits the ability to make definitive conclusions about the possible pharmacodynamic (PD) differences between canagliflozin and dapagliflozin.
In addition to inhibition of renal SGLT2 leading to increased UGE, the 300‐mg dose of canagliflozin has been shown to lower postprandial plasma glucose (PPG) and insulin concentrations by delaying intestinal glucose absorption 9. This effect is thought to be attributable to transient inhibition of intestinal sodium glucose co‐transporter 1 (SGLT1), which occurs shortly after the drug is administered and when intraluminal gut drug concentrations are predicted to be high. The delayed rise in PPG and insulin seen with canagliflozin doses of 300 mg or higher was not observed with doses ≤200 mg 4. Although no data have been published describing the effects of dapagliflozin on intestinal glucose absorption, it has been hypothesized that dapagliflozin 10 mg would have no effect on intestinal SGLT1 because of the greater selectivity of dapagliflozin for SGLT2 compared with SGLT1 (the SGLT2:SGLT1 half‐maximal inhibitory concentration [IC50] ratio is ∼1400 for dapagliflozin 10 compared with ∼160 for canagliflozin 11), and the lower doses of dapagliflozin used compared with canagliflozin.
I tried Canagliflozin for a few months. Stopped because of side effects. Two main effects I noted which were not at all surprising- increased hunger and fatigue.
I guess take it half or 1/3 the time then? Don’t totally cut it off
What. Analysis of a trial that used the drug canagliflozin found that as people lost weight, their appetite increased proportionately, leading to consumption of more calories and weight loss plateau (leveling off).Oct 14, 2016
1 Like