#262

Many people who take metformin for “longevity” don’t take rapa. And among those who take rapa, I still don’t get the reasoning as they could take acarbose instead. They take rapa + acarbose, and their glycemic control is still not optimal, SGLT2i seem a better option. I can only imagine metformin 500 mg XR as being useful for someone on rapa + acarbose + SGLT2i with suboptimal glycemic control. Did I miss something?

2 Likes
#263

Yes. I am on Rapa + Acarbose + SGLT2I + Metformin. :slight_smile:

I agree that Metformin alone for longevity isn’t effective.

1 Like
#264

Have you considered GLP1-RA? If so: why metformin instead of oral semaglutide 3 mg (for instance)? (I don’t say that semaglutide is better, I’m just curious)

#265

Best used in combination with SGLT2i.

#266

Actually I have been considering a GLP1-RA. Which one do you recommend? I don’t want an injection though.

I may switch out the Metformin for it. Unfortunately that means I’ll be dumping about a 3 year supply of Metformin because I overstocked. :sweat_smile:

#267

That’s also my guess/bet but for now we don’t have RCT on this. Just longitudinal studies that point to some incredible results.

@DeStrider: I can’t recommend anything because I don’t know enough. If you don’t want an injection then the only option is oral semaglutide (Rybelsus). The issue might be if you’re underweight or close to.

1 Like
#268

If you are a non-diabetic - which I believe is the case, I’m personally not prescribing metformin unless there is another indication (PCOS for example).

The GLPs have the issue of weight loss. But I have several individuals who are at ideal body weight on low dose semaglutide or Tirzepatide. For those with PD I’ve been doing dulaglutide, but with the article @adssx recently posted, ?semaglutide might end up being better despite getting no brain levels - we will have to see.

I find most people don’t lose much weight on up to 0.25 to 0.5 mg weekly of Semaglutide. With Tirzepatide, often 1.5 mg weekly does fine. Naturally, if there is weight to lose, then escalating doses is typical to achieve ideal body weight, then back off to a maintenance dose.

Compounders can make a sublingual liquid with semaglutide, and dosing 1 mg daily seems to be near as good for weight loss for many individuals as a modest injectable dose. The standard oral semaglutide tablets are the only oral form that I know of that is standard Rx.

The biggest issue for many, is getting a cost effective access to these drugs, which have an incredible profit margin.

5 Likes
#269

I am a non-diabetic, but I am just in the pre-diabetic range. Honestly, I would love to lose 20 lbs to get to my ideal weight. @DrFraser what dose of oral semaglutide would you recommend to lose this amount of weight over a year?

1 Like
#270

Based on my family history chock full of PD/ALS, and that I have e3/e4, does this mean I shouldn’t be on metformin? This is the first I’m seeing anything about the metformin/PD connection.

Also, @DrFraser?

Thanks for posting this… I learn so much here!!

Edit:
Just found this… without reading the study (my ADD prevents getting through one!) this one particular source seems to suggest it helps unless it hurts :slight_smile:

2 Likes
#271

FWIW, I recently started a sub .25 dose of (injectable) semaglutide and am eating more calorie dense foods in order to eat enough.

Perhaps it’s because I’m sensitive, or maybe it’s because of my WFPB diet which has me eating a huge volume of food (which I love) and the huge volume has become less appealing?

N=1, and YMMV.

1 Like
#272

Simple. Because nothing controls glucose as well as metformin for most people.
Metformin is just simply the most proven and studied glucose medication. It’s safety is unquestioned. I don’t know why you use such an unscientific term as “dirty drug”.
Because a drug affects things other than the primary target, it does not mean that the other effects are harmful.
Simply put, most other glucose control drugs are just NOT as effective as metformin.

2 Likes
#273

Metformin is essentially extra from French lilac?

#274

image
image1172×1290 261 KB

Yes for glucose control, no for longevity.

5 Likes
#275

“Most” people is the operative word here, because it’s certainly not all. Of course hardly surprising as it’s a rare drug that works as intended for all people.

For example, I took metformin 500mg/day for about a year. I was (and still am) prediabetic with A1c of 5.9 and FBG of about 110-115. I tolerated the metformin well, basically felt zero side effects.

Well, the metformin did absolutely zilch for me. Nothing. My fasting blood sugar didn’t budge, nor my A1c. It’s as if I took an air pill. To be clear, my diet was (and still is) very good, low calories (I don’t overeat), plenty of fiber, no extra sugar, whole plant predominant (mediterranean pescatarian) etc., and I exercise (cardio and weights), no smoking, street drugs, very little drinking.

Now, maybe if my dose was upped, I’d see some effect, but by the time the year passed, I had read enough about metformin that I was no longer interested. I was put off by what I read about metformin’s impact on exercise, by the fact that in preventing the transition from prediabetes to diabetes, it was substantially worse than lifestyle interventions, and by the fact that the initial hype about metformin was based on a single severely - fatally - flawed study (that purportedly showed diabetics on metformin living longer and with less cancer than non-diabetics). I was completely disenchanted with metformin even before Peter Attia abandoned it.

So I quit metformin in disgust, and I’ve been looking for something better. I’m very happy it works for so many alas it’s not for me.

2 Likes
#276

I’m with @desertshores on metformin. It has a very long history and has been studied extensively with many positive benefits. “dirty drug” to me is a good thing, as the benefits are spread over many targets. Despite what Kaeberlein said about “Rapamycin is a specific, clean mTOR inhibitor.” evidence shows that like caloric restriction, rapamycin has multiple positive effects over different pathways. That’s good, whether you call it “dirty” or not. The problem with metformin is that it may be more “confusing” or “mysterious” despite it’s long history. But in large overviews it appears to be positive with very little downside - just hesitancy to make any sweeping pronouncements until the MILES (Metformin In Longevity Study) and TAME (Targeting Aging with Metformin) results come in. My experience with metformin on muscles was no noticeable effect whereas that wasn’t true with statins.
**Here are 2 recent general public articles on metformin and 2 large overview studies (Meta-analysis), all positive (with some reservations).

A cheap drug may slow down aging. A study will determine if it works

https://www.npr.org/sections/health-shots/2024/04/22/1245872510/a-cheap-drug-may-slow-down-aging-a-study-will-determine-if-it-works

Is metformin a wonder drug?

https://www.health.harvard.edu/blog/is-metformin-a-wonder-drug-202109222605

A Critical Review of the Evidence That Metformin Is a Putative Anti-Aging Drug That Enhances Healthspan and Extends Lifespan

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8374068/

Metformin: Is it a drug for all reasons and diseases?

https://www.sciencedirect.com/science/article/pii/S0026049522001019

1 Like
#277

Compared with tirzepatide that prevents diabetes with 94% efficacy in people with diabetes and overweight (TBC in people who only have prediabetes): https://www.google.com/amp/s/amp.cnn.com/cnn/2024/08/20/health/tirzepatide-diabetes-lilly-trial

2 Likes
#278

Tirzepatide also has many nasty side effects such as muscle loss along with the fat loss. Also, when you stop taking it, you gain 75% of the weight back, but unfortunately the regain is all fat and not the muscle (unless you’re hitting the gym hard). I’d rather take Metformin or an SGLT2I.

Tirzepatide is also an injection and quite expensive compared to oral Metformin which is one of the cheapest meds available. This makes Metformin superior for the mass public.

1 Like
#279

Dont SGLT2Is have the same effect?

1 Like
#280

No, SGLT2I causes you to excrete more glucose, sodium and lithium. Tirzepatide and GLP1 agonists cause you to lose your appetite and eat less. Eating less causes fat and muscle loss. Excreting glucose shouldn’t affect muscle mass as far as I know.

2 Likes
#281

I’ve lost 20 pounds on low dose tirzepatide, but only 0.5 pounds of that was muscle mass (per DEXA). If you maintain protein intake and resistance training, it will be ok.

Side effects and cost of low dose tirzepatide are both quite low.

3 Likes