#168

A new study showing the effectiveness of Canagliflozin (and SGLT2 inhibitors in general) for weight loss. I found this to be true in my experience using canagliflozin and empagliflozin; they were good for a quick 10 to 15lb loss (when I was at 175lbs) over the first month of use, but then the weight loss stopped.

In proof-of-concept trial, J&J’s Invokana combo helps non-diabetics shed significant weight

In diabetes trials, Johnson & Johnson’s Invokana has helped some patients lose weight–sometimes more weight than they did on another diabetes treatment. Could the drug work for weight loss in patients without diabetes?

The answer was yes in a Phase II trial presented Saturday at the American Diabetes Association Scientific Sessions. The proof-of-concept study showed that combining Invokana (canagliflozin) with the older weight-loss med phentermine delivered a 7.5% loss of body weight.

The 334-patient study tested the two-med combo against phentermine alone, canagliflozin alone, and a placebo. After 26 weeks, patients using the combo had lost 7.5% of their body weight, compared with 4.1% in those taking phentermine alone, 1.9% of those only taking canagliflozin, and 0.6% of placebo patients.

Also, almost two-thirds of the patients taking both drugs reduced their body weight by at least 5%, compared with 17.5% of placebo patients.

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#169

10 or 15 pounds seems like a lot for SGLT2 inhibitor alone. Were you taking/doing anything else differently in addition to the SGLT2i? In that study, the canagliflozin-only group only lost 1.9% of body weight, which would be maybe 3 or 4 pounds for the average person, and also we don’t know how much of that weight is fat vs lean mass. Still, anything that can help get rid of excess body fat while also potentially extending health span/life span is a winner in my book, as long as those scary-sounding side effects like Fournier’s Gangrene are extremely rare.

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#170

Personally I don’t have the experience of weight loss after taking 10mg Empagliflozin every day for 4 months. (Body weight ~92lbs the past years).

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#171

New study:

#172

Did you take both at the same time and what was your dose? Thanks!

#173

No - I started at 100mg Canagliflozin, then after a few week went up to 300mg. Stayed there for a number of months. Then moved over to Empagliflozin (10mg/day). See: Canagliflozin for Anti-aging (part 2)

#174
#175

I know Canagliflozin can sometimes bring up fatigue; has the same side-effect been expressed with regard to Empagliflozin? I use 10mg Empagliflozin per day, albeit those days I forego the Empagliflozin I don’t feel any better. (I had fatigue-issues in the past. Rapa seemed to have given me back some of my stamina I lost for years, but the past period the all-overwhelming fatigue has returned. Not sure what to make of it).

#176

Its a rare side effect of canagliflozin. Since I’ve moved to empagliflozin I’ve had no issues on it, as I did with canagliflozin. But, I’ve not done any indepth research on the issue. If I run into it at any point, I’d just stop using empagliflozin. If you are suffering from fatigue, perhaps try pausing it for 3 or 4 weeks as a test, to see if anything changes for you.

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#177

Thanks Rapadmin. Good to hear changing to Empagliflozin solved this issue of fatigue for you.

#178

Can anyone share how much weight they lost on empagliflozin? I really want to drop 10 lbs, but my body isn’t listening. Thanks. :slight_smile:

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#179

I gained weight ;-). But I just seem to have have more hunger in general - as a result of the cold over here.

#180

i lost ten pounds on 100 mg Canagliflozin on the first month, but no more weight loss after that. i am taking Cana or Empag now just to maintain the current weight. I read someone took 300mg Cana and lost 10 Kilos after three months. Cana seems to be more effective in weight reduction.

#181

I lost 10lbs or so very quickly - 2 to 3 weeks after initiating, then no more after that. I had even more luck with metformin; about 15lbs over a few months. Apparently it works well as an appetite supressant. If those don’t work for you - I’d look into semaglutide and similar GLP1 inhibitors: Intermittent (oral) Rybelsus / Semaglutide use in healthy individuals?

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#182

I’m sure you’ve considered chronic fatigue syndrome which worsens with physical or mental activity and shares certain traits of migraines such as headaches and light sensitivity.

#183

@rivasp12 Thanks! Indeed, I have. In fact I was diagnosed with an autoimmune disease previously, and I have always thought the overwhelming fatigue may have an autoimmune component to it. But since it is apparently difficult to pursue a CFS/ME diagnoses where I live, I have not felt inclined to try. After years wherein I had tried to target inflammatory pathways through diet, exercise, fasting, many herbal supplements without any noticeable effects, Rapamycin really seemed to mark a change for me in terms of fatigue. But perhaps my dosing has been a bit off, and admittedly lingering depression also seems to have an impact on my energy levels.

#184

Yes, it’s so involved since depression can give fatigue, but then again so many physical things can lead to depression.
Sometimes I just try provigil to see if it helps.

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#185

@rivasp12 You are definitely right - it seems a bit like a vicious circle trying to find what is cause and what is effect. I’m also not sure whether my circadian rhythm may be involved. Whereas I can be exhausted during the day, I seem to feel more awake at night. In addition I was diagnosed with secondary adrenal insufficiency a few years ago, so I’ve also wondered whether my ACTH/cortisol levels may still be off during times of the day. If it would be easier to get a melatonin and day curve ACTH/cortisol level test here, I’d probably pursue that also.
Sorry, either way, all in all, I can definitely not say with certainty the Empagliflozin has anything to do with this. After all that severe fatigue had been present for years. Thank you so much for the suggestion. It sounds like a good idea to ask my GP whether he wants to prescribe Provigil - it may definitely be worth a try.

#186

Granted, these were older patients with a prior history/risk of cardiovascular disease, low baseline eGFR-levels, but are there any other more recent studies indicating SGLT2-inhibitors may affect bone mineral density? They mention a decrease in estradiol levels in females taking Canagliflozin in this study also.

Conclusions:

Fracture risk was increased with canagliflozin treatment, driven by CANVAS patients, who were older, with a prior history/risk of cardiovascular disease, and with lower baseline estimated glomerular filtration rate and higher baseline diuretic use. The increase in fractures may be mediated by falls; however, the cause of increased fracture risk with canagliflozin is unknown.
[…]
As reported in a separate article in this issue, results from a phase 3 study in older patients aged 55 to 80 years with T2DM demonstrated that canagliflozin was associated with a small but statistically significant reduction in bone mineral density (BMD) at the total hip (but not at other skeletal sites) over 104 weeks and increases in the bone turnover markers serum collagen type 1 β-carboxy-telopeptide (β-CTX), a resorption marker, and osteocalcin, a formation marker (19). Previous studies have demonstrated a link between weight loss, decreased estradiol levels, increased bone turnover, and decreases in BMD, possibly due to decreased estrogen production (20–24); weight loss and reductions in serum estradiol levels were seen in women treated with canagliflozin (19), which may explain the increases in bone turnover and decreases in total hip BMD observed with canagliflozin treatment.

#187

Caloric restriction promotes longevity in multiple animal models. Compounds modulating nutrient-sensing pathways have been suggested to reproduce part of the beneficial effect of caloric restriction on aging. However, none of the commonly studied caloric restriction mimetics actually produce a decrease in calories. Sodium-glucose cotransporter 2 inhibitors (SGLT2-i) are a class of drugs which lower glucose by promoting its elimination through urine, thus inducing a net loss of calories. This effect promotes a metabolic shift at the systemic level, fostering ketones and fatty acids utilization as glucose-alternative substrates, and is accompanied by a modulation of major nutrient-sensing pathways held to drive aging, e.g., mTOR and the inflammasome, overall resembling major features of caloric restriction. In addition, preliminary experimental data suggest that SGLT-2i might also have intrinsic activities independent of their systemic effects, such as the inhibition of cellular senescence. Consistently, evidence from both preclinical and clinical studies have also suggested a marked ability of SGLT-2i to ameliorate low-grade inflammation in humans, a relevant driver of aging commonly referred to as inflammaging. Considering also the amount of data from clinical trials, observational studies, and meta-analyses suggesting a tangible effect on age-related outcomes, such as cardiovascular diseases, heart failure, kidney disease, and all-cause mortality also in patients without diabetes, here we propose a framework where at least part of the benefit provided by SGLT-2i is mediated by their ability to blunt the drivers of aging. To support this postulate, we synthesize available data relative to the effect of this class on: 1- animal models of healthspan and lifespan; 2- selected molecular pillars of aging in preclinical models; 3- biomarkers of aging and especially inflammaging in humans; and 4- COVID-19-related outcomes. The burden of evidence might prompt the design of studies testing the potential employment of this class as anti-aging drugs.

Repurposing SGLT-2 Inhibitors to Target Aging: Available Evidence and Molecular Mechanisms

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