Empagliflozin - no side effects that I can notice.
I would be willing to bet you take supplements or medications that are more dangerous than SGLT2 inhibitors.
The risk-reward ratio falls heavily on the side of canagliflozin and empagliflozin.
I do not understand your concern about these proven drugs. As I said before, aspirin is probably more dangerous.
" Risks should not be evaluated without considering attendant benefits."
"What causes Fournier’s gangrene?
Fournier’s gangrene can occur when a person has a skin wound that allows bacteria, viruses, or fungi to get deeper into the body. Examples of these skin injuries include anorectal abscesses, surgical incisions, diverticulitis, rectal cancer, or genital piercings."
"20 to 70 percent of those with Fournier’s gangrene have diabetes. An estimated 25 to 50 percent have an alcohol use disorder."
"About 1.6 out of 100,000 males will get Fournier’s gangrene"
“Fournier’s gangrene is a rare disease. Very few people with diabetes should get this bacterial infection.”
Fournier’s Gangrene: Causes, Symptoms, Diagnosis & Treatment.
This is only here because I quoted from it.
3 Likes
Please don’t use this forum as a tool to disparage NPs and PAs. Malpractice claim rates are far lower for PAs and NPs compared with physicians:
Anyone can make a bad decision (including a doctor), but it doesn’t mean the entire profession should be held accountable for it.
4 Likes
Is there an argument to be made for using Canagliflozen over Empagliflozin for our purposes?
As I’m understanding it, there’s a lot more research on Canagliflozin, which is its main positive. However the risk profile for Empagliflozin is better and the assumption is that Empagliflozin would have performed similarly. So, advantage: Empagliflozin. Correct?
I’m thinking it would be a good/logical approach to take an SGLT@ inhibitor, likely Empagliflozin, on a similar schedule as Rapamycin and, additionally, take acarbose prior to any medium/high carb meal? Is my thinking correct?
I’m new here and my head is kinda spinning for the wealth of information. I’ve been taking Metformin, but it seems that these are better options (I’m not T2D, btw).
1 Like
I’m not looking to disparage all NPs nor am I saying physicians make no bad decisions.
I’m simply pointing out a safety risk.
It’s not just one article. I’ve personally just seen enough to be extremely wary, including multiple family members who were prescribed contraindicated meds, given completely incorrect advice, inappropriate testing ordered, etc.
Even the NPs know about the online-only 100% acceptance rate diploma mills that are allowed to see patients as independent practitioners with no physician supervision in most states:
As for your cited study, it’s pointing to something very different than what you’re claiming.
Supervising physicians are the ones who take the hit, and it’s no surprise to me that physicians also tend to see more high-risk patients who are more likely to bring about something. Just because something is on the NPDB database does not mean much. A large number of claims on the NPDB are dropped and do not result in any awards.
If you look at the paper you cited it says “Diagnosis-related malpractice allegations varied by provider type, with physicians having significantly fewer reports (31.9%) than PAs (52.8%) or NPs (40.6%) over the observation period.” and that’s with the more complex patients.
I think the key positive for canagliflozin is that it was the molecule that was tested in the ITP and had the positive lifespan results. Empagliflozin (and other SGLT2 inhibitors) are expected to perform similarly by most people, but there is a chance that it won’t or doesn’t. Its similar to Rapamycin vs. Everolimus. All the lifespan tests have been done on rapamycin, but everolimus is very similar to rapamycin, seems to function very similarly, and is likely to have the same lifespan effect. But… there is a small chance that it doesn’t have exactly the lifespan improvement effect or level of impact.
I tried canagliflozin but had what seems to be a relatively rare side effect of extreme exhaustion, so after 3 months I changed over to empagliflozin. Same benefits without that side effect (for me). More details here: Canagliflozin for Anti-aging - One Month and 4 Month Updates
2 Likes
Fournier’s gangrene is deadly - literature cites ~20-80% mortality. The survivors aren’t doing too great either - serious surgery or amputations are common.
A third or so is due to an immunocompromised state (excluding diabetes). Many men. Especially older.
The impact is large enough to be concerned about when you run the risk factors. It’s not just FG, there are risky associations i.e. urosepsis and hypoglycemia (leading to coma or death). If it was just minor side effects - it’s possible to bounce back. Can’t bounce back if death occurs.
About 2 in 10000 young men have neutropenia. Yet why have antibiotics on hand if the absolute risk is so low for the population? The individual =/= population.
When I was taking 2g of metformin daily, I experienced hypoglycemia. I found out when I thought I was having a heart attack and went into the hospital and we found out it was from the metformin. Reduced to 1g a day and symptoms got better. Went to 500 mg a day and even better. Now I cycle 500 mg every other day with no symptoms.
3 Likes
“Just because something is on the NPDB database does not mean much.”
Exactly! Who needs to worry about data when you’ve got countless anecdotes and scare tactics?
If you read your own cited study - they do mention that as a limitation of the study.
“If you look at the paper you cited it says “Diagnosis-related malpractice allegations varied by provider type, with physicians having significantly fewer reports (31.9%) than PAs (52.8%) or NPs (40.6%) over the observation period.” and that’s with the more complex patients.”
From my reading of the abstract, it appears the physicians had roughly 10 times the rate of malpractice claims than the PAs (for instance). So if for 10,000 PAs you have 10 malpractice claims and 50% of those are for diagnosis, that’s 5 misdiagnosis claims per 10,000 PAs. For 10,000 physicians you have 50 malpractice claims but “only” 30% of those are for diagnosis, that’s still 15 per 10k vs 5 per 10k = 3x the rate of diagnosis malpractice claims. I don’t see any data showing that physicians see more complex patients or that this is a factor.
1 Like
Not arguing, just trying to understand the fixation on a potential side effect that occurred in 12 people out of 1.7 million patients over 5 years.
From what I read, we really don’t know anything about these patients except that they were taking SGLT2 inhibitors= they had diabetes and, thus, maybe had very compromised health.
Also, the FDA warning says that Fournier’s gangrene occurs in 1.6 out of 100,000 US males. Unknown data for females, but that = 27.2 occurrences per 1.7 million. Obviously considerably higher than the 12 cases. This seems to imply that OTHER diabetes drugs like Metformin must be protective of Fournier’s gangrene, NOT that SGLT@ inhibitors are implicated as causal.
Or am I totally misunderstanding something here???
1 Like
Each of us will have different risk profiles so I think its fine that @tongMD finds the risk for SGLT2 inhibitors unacceptable; at age 30, that is not a completely unreasonable view of risk/reward thought it may be different than my own.
I think what we really want to focus on is trying to identify is the true likely range of the risk (Incidence per 1000, or 10,000, etc., and each person will make his or her own decision as to whether that risk is acceptable for them given the perceived potential benefit.
As stated, on this page the risk from the FDA is “reported” cases being 12 patients out of 1.7 million patients over 5 years from this document linked below. It seems possible, even likely, that this is not the full number of patients who got Fournier’s gangrene while taking SGLT2 inhibitors. Perhaps we want to use something like 170 patients as a worst case guess of the true number to be conservative. So - 170 over 1.7 Million over 5 years. This translates to 1 in 10,000 patients getting the disorder.
Some other points that are relevant:
- It typically starts within a few months of initiating the SGLT2 inhibitor - so it seems risk go down if you’ve been taking it for a year.
- Happens more frequently to men between age 50 and 79
Additionally, it suggests:
Publications report that Fournier’s gangrene occurs in 1.6 out of 100,000 males annually in the U.S., and most frequently occurs in males 50-79 years (3.3 out of 100,000).1-3 In our case series, however, we observed events in both women and men.
This number includes only reports submitted to FDA* and found in the medical literature,4-6 so there may be additional cases about which we are unaware. In 2017, an estimated 1.7 million patients received a dispensed prescription for an SGLT2 inhibitor from U.S. outpatient retail pharmacies.7 Although most cases of Fournier’s gangrene have previously been reported in men, our 12 cases included 7 men and 5 women. Fournier’s gangrene developed within several months of the patients starting an SGLT2 inhibitor and the drug was stopped in most cases. All 12 patients were hospitalized and required surgery.
A 1 in 10,000 risk is something that doesn’t really concern me too much. But for other people that may be an unacceptable risk. Thats fine - I’m not here to convince anyone, I’m just here to try to understand the potential risks and rewards as clearly as possible… and these types of discussions really help with that so I appreciate everyone’s input.
And, I’ll just keep this in mind:
Patients should seek medical attention immediately if you experience any symptoms of tenderness, redness, or swelling of the genitals or the area from the genitals back to the rectum, and have a fever above 100.4 F or a general feeling of being unwell. These symptoms can worsen quickly, so it is important to seek treatment right away.
And also to keep in mind the other risks I face on a regular basis:
| Lifetime odds of death for selected causes, United States, 2020 | |
|---|---|
| Cause of Death | Odds of Dying |
| Heart disease | 1 in 6 |
| Cancer | 1 in 7 |
| COVID-19 | 1 in 12 |
| All preventable causes of death | 1 in 21 |
| Chronic lower respiratory disease | 1 in 28 |
| Opioid overdose | 1 in 67 |
| Suicide | 1 in 93 |
| Motor-vehicle crash | 1 in 101 |
| Fall | 1 in 102 |
| Gun assault | 1 in 221 |
| Pedestrian incident | 1 in 541 |
| Motorcyclist | 1 in 799 |
| Drowning | 1 in 1,024 |
| Fire or smoke | 1 in 1,450 |
| Choking on food | 1 in 2,745 |
| Bicyclist | 1 in 3,396 |
| Sunstroke | 1 in 6,368 |
| Accidental gun discharge | 1 in 7,998 |
| Electrocution, radiation, extreme temperatures, and pressure | 1 in 14,705 |
| Sharp objects | 1 in 26,744 |
| Cataclysmic storm | 1 in 35,074 |
| Hot surfaces and substances | 1 in 50,341 |
| Hornet, wasp, and bee stings | 1 in 57,825 |
| Dog attack | 1 in 69,016 |
| Lightning | Too few deaths in 2020 to calculate odds |
Sources:
3 Likes
So you didn’t read the paper before citing. This is going nowhere. Let’s agree to disagree.
1 Like
These are all fair points. I think it’s fair to say the older one is - the amount of theoretical disability-adjusted life years (DALYs) left is likely lower. I can’t imagine the urgency one can feel with remaining life expectancy, functional status and quality of life. Generally, people have a bias towards interventionism in these types of situations that should be evaluated in depth because interventionism in the context of treatment complexity tends to cause harm more often than we expect and many people do not recognize the limitations of evidence base in interpreting the medical literature.
Let me further explain my risk management approach when it comes to these uncertainties because it vastly changes the risk-reward equation when we think about cumulative tail risks instead of traditional risk management approaches that rarely address tail risks (most of the time these are ignored despite sizable impact).
When we cite statistics here about “healthy people”, it’s not from people using multiple drugs. The vast majority of “healthy” people aren’t under polypharmacy. Not to mention older “healthy” people here can have different physiology especially when it comes to possible “inappropriate polypharmacy”. And geriatricians are extremely few in numbers relative to the geriatric population that can even be qualified to address these medical management issues at an expert level.
Why do we care about polypharmacy? “Inappropriate polypharmacy” contributes to roughly 100,000 deaths per year and that’s an underestimate IMO. Insurance companies increasingly recognize it and pay for medication review for prevention because it’s very high impact.
It’s not as high as heart disease, but it’s on par with the top 5 or so. It’s probably higher than heart disease when you include optimal treatment, prevention strategies, and low risk experimental therapies. Note that the cause of death is usually whatever we write on it as the best guess. Nobody knows for sure even with path doing a biopsy and we don’t list all the contributing factors. When we go with unproven off-label use of multiple drugs, the statistics that apply to the normal population should get thrown out quickly.
As for individual rare events, I personally look at both death and disability-adjusted life years. A single episode of something like urosepsis is a huge impact even if it might be 0.5% or so incidence in the population. Possibly reversible impaired spermatogenesis if it even occurs is negligible to me in terms of DALYs. We can also think about it in terms of insurance - would you rather risk a category 5 hurricane at roughly a 1% chance per year or pay insurance for it? I would not. But people tend to become weirdly resistant to insuring for these sort of rare events that aren’t even that rare over a lifetime (30% chance). And that’s even if say insurance messed up the underwriting and gave favorable odds - a guaranteed investment.
Also, note that diseases that are “rare” are very much important to think about. These tail risks aren’t even 1%, but much higher when we run them cumulatively.
Most physicians are not familiar with a large number, if not the wide majority of rare diseases. I’ve seen a case of a lady that had Sjogren’s and it was missed by over 10 physicians (we have Epic Care Everywhere, so I’m sure based on the records - a relatively new feature that allowed me to deduce her condition) despite clinical symptoms being unambiguous. But to be fair, most physicians aren’t spending more than a bit of time digging the charts let alone all the possible medical records plus maybe 5-10 min in the patient’s room. Most physicians put all “rare diseases” on the low to zero priority list to read up on.
When you add all the “rare diseases” cumulatively, rare iatrogenic events, rare medication adverse events, and rare accidents (not motor vehicle accidents or other common accidents) - it can easily be 10%+ of patients that come in. And nearly all of them may not be getting optimal treatment that actually has a sizable impact on DALYs or death. I’ve literally caught a elderly woman with psychosis on a beta blocker as they were about to give her an antipsychotic which would have creeped onto the polypharmacy death and disability problem.
Meanwhile, we do not know if rapamycin plus canagliflozin and all the other things will actually extend DALYs relative to rapamycin in humans. Or even if rapamycin will extend it in the first place in humans. It’s a shot in the dark with our best guesses, currently monotherapy with rapamycin is considered suggestive evidence and not even up to a weak recommendation by consensus. If you look at various researchers in the field - about half or so are stating they are not taking rapamycin.
3 Likes
I don’t have access to the full paper, but if you do and it says anything that contradicts what I said above, please feel free to share.
Great book about this called Death of Expertise by Tom Nichols.
“Online debates become personal, emotional, and irresolvable almost as soon as they begin.”
“Feelings are more important than facts: if people think vaccines are harmful, or if they believe that half of the US budget is going to foreign aid, then it is ‘undemocratic’ and ‘elitist’ to contradict them“
Your book
1 Like
full quote
“Americans now think of democracy as a state of actual equality, in which every opinion is as good as any other on almost any subject under the sun. Feelings are more important than facts: if people think vaccines are harmful, or if they believe that half of the US budget is going to foreign aid, then it is “undemocratic” and “elitist” to contradict them.”
I like this one best:
“Unable to see their own biases, most people will simply drive each other crazy arguing rather than accept answers that contradict what they already think about the subject. The social psychologist Jonathan Haidt summed it up neatly when he observed that when facts conflict with our values, “almost everyone finds a way to stick with their values and reject the evidence.”
4 Likes
Agreed, sounds like a great book, but what’s the relevance to the current discussion?
Also, the “democratization of knowledge” is what enables a forum like RapaNews, presumably composed of mainly non-medical professionals, to engage in rational discourse despite coming from a variety of educational levels and backgrounds. A book such as The Death of Expertise could be seen as an elitist slap in the face to those who are actually taking the time and effort to understand and engage.
1 Like