'Sulfur burps' and other GLP-1 things we're learning

[00:00] Adam:

[00:03] it's Adam Ragusea, and yes, my weight is yo-yoing 

[00:12] grew a social movement to de stigmatize fatness. 

[00:19] Advance Fat Acceptance, which most famously 

[00:26] bigger seats for big bodied people. You also get 

[00:32] which pushes this public health frame 

[00:39] health at every size people observed is that 

[00:45] discriminated against in the healthcare system.

[00:52] and it goes something like this. What did the 

[00:56] wound? Have you tried diet and exercise? It's 

[01:04] this claim that doctors tend to look at a person 

[01:09] their obesity. And what obese people have 

[01:16] health problems that have nothing to do with my 

[01:20] Number two, even if my health problems are related 

[01:29] by the study outcomes, it is nearly impossible 

[01:35] off without serious medical help, so let's not 

[01:41] almost impossible before you start treating me 

[01:49] Over on the other side of this particular 

[01:55] saying this is all hogwash, it's very well 

[01:59] a lot of extra body fat have much worse health 

[02:06] It is not possible to be healthy at every size. 

[02:14] seen an enlightened consensus emerge where we 

[02:21] of bad things, but fatness is not necessarily the 

[02:29] diabetes, and kidney disease, and non-alcoholic 

[02:35] in a dense web of causality that we now call 

[02:42] is at most an imperfect proxy for the total 

[02:48] to be fat, but they're not always fat, and the 

[02:54] is murky. Anyway, I think the emergence of that 

[03:01] bit between the fat acceptance crowd and the fat 

[03:10] Speaking of consensus, we cannot seem to form one 

[03:18] GLP-1 drugs, but that's not quite right. These 

[03:26] that all our bodies produce to make us feel full 

[03:32] drugs also imitate different peptides like GIP, 

[03:38] and there are more things like that on 

[03:42] incomplete. It's like calling all of my cups 

[03:50] You could call these drugs incretin mimetics. 

[03:56] regulate blood sugar and appetite are known 

[04:02] imitates another thing, which is what these 

[04:08] But, incretin mimetic is even harder to say out 

[04:17] hasn't caught on among the general public.

[04:24] weight loss drugs because they are the only safe 

[04:32] and long-lasting effects. These are the only 

[04:39] to any reasonable, real world standard of what it 

[04:47] them the weight loss drugs, they're the weight 

[04:52] views these drugs with some amount of suspicion. 

[04:59] of money selling false hope to generations of 

[05:07] which seems to be the case this time, the body 

[05:12] will reinforce a toxic, thin ideal in society. 

[05:21] to that ideal since, hey man, all you need to 

[05:27] which is still extremely expensive and 

[05:34] I am, as you can tell, very sympathetic to the 

[05:41] the ongoing research on these drugs points to 

[05:47] should view as something of a vindication. The 

[05:55] because these drugs work even if you aren't 

[06:03] of fatness. In clinical trials, in people who 

[06:09] to lose weight, we are still seeing dramatic 

[06:15] health, brain health, addiction, substance abuse 

[06:22] whys and the hows, but it sure seems like these 

[06:29] weight to be essentially correct. If a drug treats 

[06:36] impacting weight, if you get healthier on these 

[06:42] the same, that would indicate that weight is only 

[06:52] I think that body acceptance advocates should 

[06:57] just about fatness. It might not even be primarily 

[07:05] denominator here is the hormones that influence 

[07:12] psychologically. We are evolved to live a 

[07:19] the time. And so to be healthy, our bodies seem 

[07:28] or when we are not getting the hormonal signal 

[07:37] these very complicated biological systems 

[07:43] drugs as a miracle cure, and we certainly 

[07:51] I am curious about the side effects that we're 

[07:57] are taking these drugs. I'm curious about how 

[08:03] after decades of use. And I am curious about why 

[08:13] A great expert on the internet to follow for 

[08:21] practitioner. That is a nurse whose level of 

[08:26] in the US system. He doesn't need to go through 

[08:31] David says on my channel should be construed as 

[08:38] smart guy who deals with these drugs every day in 

[08:44] reading and posting about the latest research. 

[08:51] his social links are in the description.

[08:55] be some ongoing conversations with Nurse David 

[09:02] what kind of side effects are we seeing?

[09:05] I mean, the biggest one, and the trial data 

[09:11] just informally call it the big four. So whenever 

[09:17] they'll almost always have nausea, 

[09:21] Adam:

[09:22] medication that I've heard can treat all four 

[09:26] David:

[09:30] add is usually some form of heartburn. You'll 

[09:35] my patients. You can look on Reddit, or really any 

[09:42] burps, which is just the drugs delay your gastric 

[09:50] forward, and so you get a little fermentation.

[09:54] Yeah.

[09:57] But even that, same thing, there are ways of 

[10:04] cooking side of things, pineapple, papaya.

[10:07] The enzymes.

[10:08] Yeah, the enzymes will help. And people look 

[10:13] it'll work." But yeah, that's one thing with 

[10:20] manageable.

[10:21] Yeah.

[10:22] A lot of it too in the trials is their goal 

[10:26] let's lose the most amount of weight as fast as we 

[10:35] they're really actually quite tolerable. 

[10:41] the actual absolute rate of side effects, even 

[10:49] rate. And over time, because most of the drug 

[10:57] you'll watch it just slowly drops away as 

[11:04] Adam:

[11:06] Like the new normal where we are all expected 

[11:12] real jobs. Love that, but you can make it more 

[11:18] easiest way to build a website. Do you still 

[11:25] I'm talking to in this video? I know who he is 

[11:34] I noticed it, and now he's on my channel with 

[11:39] things work. If you want to be discovered, 

[11:45] a website from Squarespace does just that.

[11:51] to help the AI chatbots find your site and 

[11:57] building the site yourself is just stupid easy at 

[12:02] prompt and just start tweaking it until it's 

[12:08] email marketing, everything that you can need 

[12:12] around with a site for free. When you're ready 

[12:18] name, save yourself 10% with my code RAGUSEA. 

[12:24] Squarespace. Anyway, we were talking 

[12:28] associated with the new weight loss drugs.

[12:33] muscle wasting, which I've understood to 

[12:38] muscle loss that you would expect with 

[12:42] David:

[12:44] medicine research, they will reference something 

[12:52] they mean you should... If you were to just crash 

[13:01] mass and about 25% lean mass.

[13:04] Yeah.

[13:04] And when you look at these drugs, it's 

[13:11] lean mass loss and the rest is fat mass loss. 

[13:18] definition of lean mass. It depends on, are you 

[13:26] the conversation with patients like, "If you are 

[13:32] in and at least do resistance training." Those are 

[13:39] things that will at least preserve your functional 

[13:44] Adam:

[13:47] by bodybuilders and people like that.

[13:51] Yes.

[13:52] They know that when you diet down, you're going 

[13:57] the weights and if you keep getting protein, 

[14:01] David:

[14:03] Adam:

[14:05] that are concerning you so far?

[14:08] There's a slightly increased risk of gallstones 

[14:18] also more related to the weight loss and not 

[14:24] but you lose weight rapidly and sometimes your 

[14:31] patients can get their gallbladder out and then 

[14:37] happened.

[14:39] And then there's the big unknown that not 

[14:44] which is what happens to people when 

[14:47] David:

[14:53] there is probably a reasonable subset of diabetics 

[15:00] time just.

[15:01] At this point.

[15:02] Yeah. I mean, liraglutide or Victoza, that was FDA 

[15:10] Adam:

[15:13] David:

[15:15] generic now. That's how long it's been around. So 

[15:22] in 2017, so we're going on 10 years for that even. 

[15:31] for a while. But even the clinical trials, the 

[15:37] and obviously we just continue to see a benefit as 

[15:44] any evidence to back this up.

[15:47] Very scientific.

[15:48] But also, I mean, it doesn't make... Just 

[15:54] Adam:

[15:55] argument. There you go. Go ahead.

[15:57] Yeah. On a mechanistic argument, there shouldn't 

[16:04] drug class, with statins, we know the longer 

[16:11] cardiovascular diseases.

[16:12] Sure yeah.

[16:13] And so I have a feeling it's going to be the same 

[16:19] 20% of your body weight and you stay on it for 

[16:25] probably have less comorbid conditions. You'll 

[16:33] and actually there's already starting 

[16:39] Adam:

[16:41] David:

[16:47] Adam:

[16:50] quality adjusted life year. We don't just want to 

[16:57] and QALY is a crude way of measuring that. It's 

[17:03] you. That's a QALY. Anyway.

[17:05] The QALY data is already starting to line up that 

[17:11] they do start paying for themselves, even with the 

[17:21] and actuaries everywhere, that's 

[17:24] Adam:

[17:26] to make a mechanistic argument, and also I suppose 

[17:32] a receptor in your body and you pummel it.

[17:35] Yeah.

[17:36] With stimulus a little bit more than it would 

[17:42] weird things happening among them. It's just going 

[17:49] that receptor feel anything.

[17:51] Yeah.

[17:52] Are we not seeing that with these drugs? We're not 

[17:56] system just equilibrates to it?

[17:59] There was a cardiovascular outcomes trial called 

[18:07] last year, and it was almost five year long 

[18:13] at cardiovascular outcomes. And they included 

[18:21] Adam:

[18:21] David:

[18:24] was about four and a half year period and there's 

[18:30] down, and if you look at the error bars and the 

[18:39] 15,000 patient trial and no one is... I don't want 

[18:49] regaining weight, not requiring a higher dose, 

[18:58] above my pay grade in terms of understanding, but 

[19:04] for some reason, there's just not that 

[19:09] with cannabinoids or opioids or various other. 

[19:21] GLP-1 as a receptor is so integral to just 

[19:31] Adam:

[19:31] David:

[19:34] it took pharmacology to realize, oh, hey, this 

[19:45] Simplistic understanding is, sure, it suppresses 

[19:50] but I mean, it is-

[19:51] Tip of the iceberg.

[19:52] Yeah, half inch view. I mean, I'm working on 

[20:01] infects, and I've been writing for a month and 

[20:05] it down to regular, in English, but also it's 

[20:11] I'm like, "Oh, wait, there's another 

[20:17] I actually found an evolutionary development paper 

[20:27] development of the GLP-1 class, or I guess I shape 

[20:38] So you get GLP-1, which everyone knows about. You 

[20:47] and you also get glucagon, and then you get a 

[20:52] that family of those three hormones are so deeply 

[21:04] really great paper that talks about some of the 

[21:11] loss, and it had the actual amino acid sequences 

[21:20] off from the primate family tree, and you could 

[21:30] Even some of the bony fish glucagon is still 

[21:36] human and get an effect. So clearly evolution was 

[21:44] I think that's my speculation as to why you don't 

[21:50] actually mission-critical to keeping you alive.

[21:55] Well, I suppose all of that is a lot of reason 

[21:59] caution.

[22:00] Yes.

[22:00] If we're dealing with such a 

[22:03] David:

[22:04] Adam:

[22:11] obesity as we know it would be over as a pandemic 

[22:21] I've got seven more years for that admittedly 

[22:31] on schedule you reckon we are. I actually 

[22:37] it is preceding the way I imagined, where you're 

[22:45] David:

[22:52] Adam:

[22:54] David:

[22:56] hullabaloo about how the rate of obesity in the 

[23:04] it's like, is that the drugs? Is that the first 

[23:11] we're starting to see a downward deflection in the 

[23:20] but at the same time, I mean, some of the 

[23:26] which is a triple agonist that will have phase 

[23:34] I mean, it's mid-April when we're recording this, 

[23:39] of June, so not too long for that. And that drug 

[23:47] Adam:

[23:49] bariatric surgery, you mean?

[23:50] Yeah.

[23:51] And by triple agonist, you mean it's 

[23:55] David:

[23:57] it acts on GIP, and then it acts on glucagon so 

[24:07] two data showed 24% weight loss at 48 weeks. There 

[24:14] weight loss at 68 weeks with patients still losing 

[24:21] data published in June will have an 80-week and 

[24:30] I mean, 29%, you're one point away from 30%, 

[24:38] loss. 30% to 35% is usually what most bariatric 

[24:47] have a drug that has that level of efficacy.

[24:56] it's pretty reasonable to expect obesity 

[25:03] there are so many other drugs in development that 

[25:11] loss, which again, like that's going to drive a 

[25:18] and not obese anymore. So yeah, I mean, by 2035, 

[25:27] obesity.

[25:28] What are you most excited about looking ahead?

[25:32] I mean, so the drug that I just mentioned, 

[25:42] the mechanism alone, I mentioned it, it acts on 

[25:51] field, they're like, "Oh, that's the drug we 

[25:59] that in this case, when you are depressing the 

[26:06] the opposite happens so it increases insulin 

[26:15] as counterintuitive as that sounds, but it also 

[26:24] like a starvation signal to your body and you 

[26:31] trials were as ethical as they are now where 

[26:38] but glucagon is the signal that comes through when 

[26:43] their insulin levels drop, and it forces 

[26:50] Adam:

[26:51] David:

[26:54] so GLP-1 basically reduces your intake through 

[27:02] basically telling your body, "Hey, grab the 

[27:08] Adam:

[27:12] decline in available calories. This is winter, 

[27:17] our whole system to this new reality."

[27:19] Yeah. So you get less intake and then you are 

[27:26] for weight loss. And then side benefit, because 

[27:34] so you will see pretty profound, again, going 

[27:42] they saw almost 25% drop in LDL cholesterol, the 

[27:48] taking a statin medication. So I look at it as, 

[27:54] lose weight and it drops your cholesterol like 

[28:00] Adam:

[28:00] David:

[28:04] a clinician like, "Oh, hey, you can take this one 

[28:12] Adam:

[28:15] you've met Nurse David and he's going to be our 

[28:21] Check his blog and his socials in the description. 

[28:26] to treat major depressive disorder, bipolar, 

[28:32] Like the man said, these drugs work on your 

[28:39] good choices with your brain and your body,