Pros and cons of GLP-1 weight loss drugs and metformin as a geroprotective agent [AMA 45 sneak peek]

In this “Ask Me Anything” (AMA) episode, Peter focuses the discussion on two topics getting a lot of attention recently. He first dives deep into GLP-1 agonists, most notably semaglutide and tirzepatide, which originally came to market as diabetes drugs but are now being studied and prescribed for weight loss. He walks through the data and compares the effectiveness of the two drugs, the side effects, and perhaps more importantly, his reservations around wide use of these drugs and who he would consider to be a candidate for them. Next, Peter discusses how metformin, another drug originally brought to market for diabetes management, gained popularity as a potential longevity drug even for non-diabetics. Peter gives his take on this possibility and reviews data from a more recent study investigating the question of whether metformin should be used for general “geroprotection.”

In this sneak peek, we discuss:
00:00 - Intro
00:08 - The hype around semaglutide, tirzepatide, and other GLP-1 agonists for weight loss
04:09 - Overview of GLP-1 agonists and why these drugs are getting so much attention
12:20 - Defining the term “geroprotective”
14:08 - Semaglutide: background, brand names, indications, and more
19:10 - Tirzepatide: background, brand names, indications, and more

In the full episode, we also discuss:
-How semaglutide and tirzepatide compare in their efficacy in terms of weight loss and other metabolic health metrics;
-Data showing sustained weight loss and improved metabolic metrics with after more than a year of using semaglutide and tirzepatide;
-What happens to body weight when a patient discontinues the medication?;
-Noteworthy side effects of GLP-1 agonists and similar classes of drugs;
-Increased resting heart rate and other concerning trends in patients using GLP-1 agonists;
-Changes in body composition (body fat and lean muscle) in patients on GLP-1 agonists;
-Possible reasons for the loss of lean muscle mass and tips for protecting lean mass;
-GLP-1 agonists and thyroid cancer;
-Who might be a candidate for GLP-1 agonists?;
-The large financial cost of this class of drugs;
-Metformin as a geroprotective drug: origin of the idea that metformin could be a longevity agent even for non-diabetic patients;
-A 2022 study on metformin sheds more light on the question of whether metformin should be used for “geroprotection” in non-diabetics;
-Peter’s current approach with metformin for his patients; and
-More.

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The Peter Attia Drive is a weekly, ultra-deep-dive podcast focusing on maximizing health, longevity, critical thinking…and a few other things. With over 45 million episodes downloaded, it features topics including fasting, ketosis, Alzheimer’s disease, cancer, mental health, and much more.

Peter is a physician focusing on the applied science of longevity. His practice deals extensively with nutritional interventions, exercise physiology, sleep physiology, emotional and mental health, and pharmacology to increase lifespan (delay the onset of chronic disease), while simultaneously improving healthspan (quality of life).

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[sunnydawn]

I started Wegovy after weight gain from quetiapine, which I must take for a mental health diagnosis. I have the side effect “insatiable appetite.” I would eat “perfectly” all day and then take seriously and eat everything… anyway my psychiatrist prescribed the Wegovy. I’ve lost 45lbs, started strength training, A1C is now 4.9 LDL 79 and feel so hopeful now for my future. 😊

[Emmuzka]

Ozempic costs here in Finland, when used not for diabetes so it's not goverment-comped, 115 Euros /month. It would be cheaper to fly from America to Finland once a month than pay the American prices out-of-pocet.

[AndreasAntics]

That’s literally how it works! It slows down your digestive system. All the information that comes in the box says so. That’s why (good) doctors also prescribe Zofran for nausea. Take your probiotics, take enzymes with your food, and eat some type of fermented food every day (kefir, sauerkraut, kimchi).

[trishdadish]

Came straight to the comments, and let me tell you, they did not disappoint! Very educational, interesting and enlightening. Worth the read in my opinion, if you’re interested in this topic (which I am).

[acfanter]

I get my script filled via a Compounding pharmacy … about $100 per month for .5 weekly semaglutide - zero insurance, zero problems. I lift heavy 3 days a week, 2 cardio, 2 recovery days. I track my food like a hawk. I am barely dropping 4 pounds a month.. But I am seeing positive body recomp. This is NOT a magic bullet - I lost 90 on keto and a 2plus hour per day exercise regime. Now working on these next 70 - for me its a tool -

[off-roadingcars]

Can you update this video, there’s a lot more information available now that wasn’t when this was made

[carlosaf]

My MD wanted me in these meds asap. I said ‘no’, started the carnivore diet in January. My weight, BP, A1c, blood glucose, triglycerides, asthma, depression, and anxiety are all down and/or gone!

[ThriveCollective]

It makes me so sad that ignorance guides most inflamed conversations about those that are using Semaglutide for weight loss appetite control reasons instead of diabetes. Diabetes is serious but so is a life long battle with compulsive overeating disorders. I’ve seen first hand the massive positive impact that Ozempic has had on a loved one that has no ability to control their appetite or compulsion to eat and binge. This drug needs to be prescribed to this alternative group of people that are just as at risk of complications and death as chronic eating disorders ruin lives and health too

[AZ]

16:44 0.25mg - you can actually dial this to 0.125mg or smaller if needed

[FoodiesVacations]

Rebelsus is the pill, I’m diabetic… but have a fear of the side effects. I don’t consider the weight loss a side effect, because I believe this is a sign that it is actually doing what it is supposed to do with your carbs. But thyroid cancer? Pancreatitis? Why would these things happen? That is what I’m trying to find out. Have not been able to find an answer.

[amyk]

I’m a NP and work at a weight loss clinic and have a masters in nutrition. These can range up to like $1400 a month and with insurance $500. Mounjaro has seemed to be the golden one, comparatively. Ppl are obsessed with these😐 BUT they have helped so many ppl lose weight who have been doing all the correct ways like proper nutrition and exercise. Insulin resistance is extremely under-diagnosed. This also aligns with PCOS. Hormones (especially with women) are a huge factor too. It’s an exciting med but I’m always skeptical and we don’t know long term impacts. So many ppl worry about the number on the scale and not the composition, so aggravating!🙄

[beverlystraus]

Tirzepatide appears to be so much more effective for weight loss than semaglutide based on my many friends & recent research.

[baribari]

The gastro side effects of oral semaglutide are apparently more unpleasant. I did not enjoy them at all. You also need bigger doses to get the same effects. But it wasn't *that* expensive here in Japan. It's about $90 a month.

[lisamaree]

But what if ya dont have a food issue? I fast 16-20hrs a day and eating high protein low sugar. My glucose number has never been over 4.5 in years! Still can’t get my weight under 80kg. I’m 52 just gone into menopause. I’m so tempted to take this medication but just don’t wanna mess with my hormones anymore than they’re changing now.

[dianed]

Metformin depletes several vitamins and minerals from the body. For example, magnesium and B12. Look it up.

[victoriaolson]

When a GLP-1 is prescribed for weight loss, are patients monitored to ensure they’re getting proper nutrition?

[chicymamma]

I was prescribed monjourno for weight loss. I was able to get 12 weeks for $50. With a coupon. I could only take 4 weeks' worth of injections, I had internal jitters and shakes so bad. I called my doc and he said, "Keep taking it, it will go away " I couldn't stand it. So, I just stopped. I did lose 5 lds. I gained 15 lbs after about 3 months after stopping monjourno. I still have jitters and shakiness. I still have the injections in my fridge. I found out shortly after I stopped that there is a shortage of this medication for people who really need it. I feel so bad.

[FoodiesVacations]

Wouldn’t an appetite suppressant work as well for non diabetic people for weight loss? Is there an appetite suppressant on the market in the form of drug or supplement?

[nutritionbyelsa]

brilliant content - enchancing my education at UBC so i can understand why im learnign matters and what it actually means for the body

[jeffchastain]

Dr. Attia, how do you feel about diabetics getting run over by rich people, who want to lose weight and can pay full price for these drugs, that are making them not available for diabetics that the drugs were developed for, and that the drugs are a crucial part of our therapy who can no longer get them because of shortages? I would love to see at least one or two of the many YouTube doctors who are talking about these drugs, and spinning up the demand for them, talk a bit about all the off label prescribing that is making diabetics have to chase these drugs from pharmacy to pharmacy, and frequently change dosages or completely change drugs or go completely without any because people are getting these drugs that should not. There is only one of these meds that is approved for weight loss.