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.
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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
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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.
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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
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@AlexKChen @Isutiger - How are you fairing with dapagliflozin? What’s been your dosage and experience? Thanks!
Thanks for asking. I’ve been on 10 mg of Farxiga (dapagliflozin) for a while now. Experience has been good. Zero negative side effects other than having to urinate more–hence I take it in the morning. Fasting Insulin and Glucose numbers are on the low end of normal. Let me know if you need more info.
That’s great to hear! @lsutiger
Do you take electrolytes with it or find your sodium depleted?
What’s your goals with taking it (longevity?) and do you use GLP1’s or anything else with it?
Heart and liver disease runs in my family so I’m considering running it as a gero-protective of sorts as well as wouldn’t mind any additional weight loss, I’m already on low dose Retatrutide and my liver numbers have never been better.
Not yet sure if it’s something I’d run all year or just for a few months out of the year. I take it you’re just staying on it?
I take this for longevity purposes. I take Rapamycin and Metformin with it.
My don’t find this depletes my sodium. I take it continuously. Let me know how you do on it if you decide to take it.
I ended up trying empagliflozin first, 10mg not every day but mostly on cheat days. My experience so far is fairly dramatic drop in blood pressure, almost fainting a few times esp after sitting for a long time. Increasing my sodium intact helped a bit with that and taking only 5mg I don’t notice the issue. Second issue is it definitely has a negative impact on my lean tissue. I feel flat and very hard to sustain my existing muscle mass even with high protein, heavy weight training, 5g creatine and 3-6g HMB daily.
I’m curious if dapagliflozin would have the same effect, I’ve read it has no or even minor positive lean tissue mass increase, which is pretty interesting if true! The effect could be due to the fact that dapagliflozin acts as a myostatin inhibitor to some extent. 1
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In studies, dapagliflozin showed smaller reductions in lean mass compared to other SGLT2 inhibitors. For example, reductions in lean body mass with dapagliflozin were less pronounced than with empagliflozin or canagliflozin over similar treatment durations - refs 2 3.
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A study comparing dapagliflozin to glibenclamide found that while dapagliflozin reduced total and lean body mass, it increased the lean-to-total mass ratio by 1.2%. This suggests a proportionally greater reduction in fat mass compared to lean mass, which is a favorable outcome for preserving muscle composition 4.
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This effect may reflect improved insulin sensitivity and metabolic efficiency in skeletal muscles.
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Low blood sugar from sglt2 inhibitor? Perhaps your glycogen is low resulting in smaller muscles and less muscle energy availability.
I take dapagliflozen 10mg daily. I haven’t had any noticeable effect for good or bad.
Yeah, insulin is anabolic so I think it’s just dropping it too far. I should measure it to see what I’m dealing with.