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GLP-1s: Overdosing, Side Effects & Long-Term Risks | Dr. Abud Bakri & Dr. Andrew Huberman

Huberman Lab Clips11:34Added Aug 31, 2026

Dr. Abud Bakri and Dr. Andrew Huberman discuss the clinical use of GLP-1 receptor agonists for metabolic health, detailing how these medications modulate bra...

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Contributed by 刘嘉琪

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  1. GLP-1 Dosing Safety

  2. 00:00We're hearing that some people I think
  3. 00:04Sam Alman actually talked about this
  4. 00:05publicly um overdose with with Cara
  5. 00:07Swisser about what he thought yeah where
  6. 00:09he overdosed actually a compound
  7. 00:10pharmacy issue he thought was what did
  8. 00:12it I trust him to do the right
  9. 00:13calculation so it does sound like that
  10. 00:15was a compounding pharmacy issue
  11. 00:16could afford it is the buy the farmer a
  12. 00:17great option
  13. 00:18I think back then people were just
  14. 00:19getting them where they can I didn't ask
  15. 00:21him why uh why that happened but
  16. 00:23nonetheless get the dosage right make
  17. 00:25sure you're getting the right stuff
  18. 00:27clean but he talked about the kind
  19. 00:29lack of uh motivation which many people
  20. 00:33have described anecdotally um like okay
  21. 00:36lowered their food drive but lowered
  22. 00:38their drive period.
  23. 00:39Yep.
  24. 00:40Makes sense,
  25. 00:41you know, depending on which pathways
  26. 00:42are being affected. But do you think
  27. 00:44that's a real effect? Is that something
  28. 00:46that people need to be concerned about?
  29. 00:47Do you think people can micro dose this
  30. 00:48stuff? Because a lot of people are micro
  31. 00:50doing it regardless of what their source
  32. 00:52is. They're taking a lot less than the
  33. 00:53kind of standard clinical trials would
  34. 00:55be. And we're leaving out Red True Tide
  35. 00:56for now. Yep. Because it's so new. We're
  36. 00:58going to talk about it, but I'm talking
  37. 00:59about the standard if
  38. 01:01semiclutinide tepide. Yeah.
  39. 01:02I'll tell you that you have your you
  40. 01:03know semiglutide which is obey and vigov
  41. 01:07is the FDA approved version for the
  42. 01:08weight loss. For teptide you have
  43. 01:10zeppbound and monero. Zepbound being the
  44. 01:12FDA approved version for weight loss
  45. 01:14that allows them to keep their patents
  46. 01:15for longer. um these medications are
  47. 01:18good kind of transforming medicine
  48. 01:19especially where where I practice right

  49. Fixing a Collapsing Medical System

  50. 01:21if you if we kind of zoom out our
  51. 01:23medical system if we didn't have these
  52. 01:25interventions was going to collapse on
  53. 01:27it itself thanks to the obesity
  54. 01:29pre-diabetes diabetes epidemics because
  55. 01:32we don't have enough clinicians or
  56. 01:33finances to get everybody who was
  57. 01:35pre-diabetic in the in the last you know
  58. 01:3720 years and they all transitioned to
  59. 01:39diabetes and ended up with you know
  60. 01:40diabetic medications and dialysis and
  61. 01:43eventually cardiovascular disease and
  62. 01:44all these things we don't have the
  63. 01:46resources to take care of all these
  64. 01:47people like our medical system was going
  65. 01:48to collapse and there wasn't enough
  66. 01:50finances to take care of it. Now these
  67. 01:52GLP1s are coming in and kind of
  68. 01:54transforming that phase of medicine
  69. 01:56because now we have a chance to
  70. 01:57dramatically change the rate of obesity
  71. 02:01uh diabetes pre-diabetes and all these
  72. 02:02cardio metabolic disorders. So where do
  73. 02:05we stand? We needed something to happen.
  74. 02:07I mean, ideally, everybody, you know,
  75. 02:09would get morning sunlight and eat only
  76. 02:10healthy foods, unprocessed foods, and
  77. 02:12have low stress and sleep great at night
  78. 02:13and maybe no one would develop to become
  79. 02:15obese. But the reality is people become
  80. 02:18overweight, obese. They get stuck in
  81. 02:20that hole. And if you just try to step
  82. 02:22out of the hole the way you came in,
  83. 02:24sometimes that doesn't work. You need a
  84. 02:25different path out of that problem. And
  85. 02:27that that's been, you know, the diet and
  86. 02:29exercise literature for the last 40
  87. 02:31years. Millions of books have been sold
  88. 02:32on how to get people leaner. We now have
  89. 02:35interventions medically that can
  90. 02:37dramatically change people's weights for
  91. 02:38the first time. We've had drugs in the
  92. 02:40past that you know 5 10% of body weight.
  93. 02:43Now with the GLP1s we're getting 10 20
  94. 02:45even 30% of body weight being shaved off
  95. 02:48of people especially with the new
  96. 02:49reduced data. Is there a free lunch?
  97. 02:51That's the big question. Like like we
  98. 02:53kind of talked about earlier there's
  99. 02:54always been these medical mishaps that
  100. 02:56have happened. So far the data is very
  101. 02:59promising when it comes to GLP1s and
  102. 03:01that we are now reversing this rate of
  103. 03:03chronic disease. Is it going to stay
  104. 03:04that way? That's a good question. I'm
  105. 03:06I'm cautiously uh optimistic when it
  106. 03:08comes to these medications. I've been
  107. 03:10prescribing them since I was a resident.
  108. 03:12Uh in my VA clinic, I was putting all
  109. 03:14these vets that are, you know, 300 lb on
  110. 03:17GLV1s, they were losing 50, 100 lb.
  111. 03:19Before it wasn't FDA approved for weight
  112. 03:21loss. We knew that that if you put
  113. 03:22diabetics on this drug, they would lose
  114. 03:24weight thanks to a lot of the
  115. 03:26bodybuilders. Um that kind of pioneered
  116. 03:28that.
  117. 03:28When did the bodybuilders first start
  118. 03:30using GLPS?
  119. 03:31Uh late 20110s. Wow.

  120. Gila Monsters & Drug Origins

  121. 03:34And then the signal I don't I don't
  122. 03:36think Norvo or Lily wanted to make these
  123. 03:38for obesity. They were focused on making
  124. 03:40diabetes drugs because like if we zoom
  125. 03:42out even further, this is another animal
  126. 03:44derived compound, right? It's found in
  127. 03:46the the saliva of the Hila monsters.
  128. 03:49GLP1 was discovered. It's too um short
  129. 03:52acting to have worked on its own. Then
  130. 03:54pharmaceutical companies, this is where
  131. 03:55you got to give pharma their credit.
  132. 03:56they developed these drugs into more
  133. 03:58functioning versions that had you know
  134. 04:00longer half- lives and could stick
  135. 04:01around in the serum for longer to have
  136. 04:03the clinical effect. So then we started
  137. 04:04noticing that diabetics like my my
  138. 04:06grandma got uh Betta which was one of
  139. 04:08these first uh GOP one drugs like 25
  140. 04:10years ago. It was the out of all the
  141. 04:12drugs she was on the reason I went into
  142. 04:13medicine that was the drug that changed
  143. 04:16her her whole trajectory because she had
  144. 04:18less insulin needs and she was losing
  145. 04:20weight and more energetic. So we had
  146. 04:22seen the effects on diabetics and then
  147. 04:24you get luraglutide dlutide and then
  148. 04:26eventually semiglutide was the is the
  149. 04:27blockbuster but you get all these

  150. Lifetime Treatment vs Weight Regain

  151. 04:30positive effects coming from these drugs
  152. 04:32on diabetics. It gets translated into
  153. 04:34obese people and overweight patients.
  154. 04:35The question is what is the long-term
  155. 04:38effect of this? Do you have to stay on
  156. 04:39this drug forever? Um can you titer it
  157. 04:41off? The the pharmaceutical companies
  158. 04:43have not given us good guidelines on
  159. 04:44that. They've shown us what happens if
  160. 04:45you stop the drug. You max out on
  161. 04:47maximum dose. Pull the brakes on. People
  162. 04:50tend to sometimes gain the weight. Some
  163. 04:51people don't, but some people will
  164. 04:53regain back to baseline. Because if you
  165. 04:54think about it, the better way to think
  166. 04:56about weight loss, it's a calculation
  167. 04:58your brain does every single day with
  168. 05:00all the different hormones and and
  169. 05:02peptides that are made from the gut, the
  170. 05:04GIP, GLP, glucagon, insulin,
  171. 05:06testosterone, estrogen, all these things
  172. 05:08kind of modulate. And there's this thing
  173. 05:09called a set point theory or settling
  174. 05:11points and they integrate should I eat
  175. 05:13or not eat, right? So the GP1 is a giant
  176. 05:17signal to the brain of don't eat. So
  177. 05:19we're we're modulating this pathway.
  178. 05:21What happens to all these young kids
  179. 05:23that are 18 19 years old on 5 milligrams
  180. 05:25of reducide uh [snorts] that have lost
  181. 05:2730 40 pounds? Are they going to have to
  182. 05:28be on that for life now to maintain that
  183. 05:31weight?
  184. 05:31Can I ask you about that? Because when
  185. 05:32people say
  186. 05:34perhaps you have to be on a drug for the
  187. 05:36rest of your life, I think okay, what's
  188. 05:37the availability? What's the cost?
  189. 05:39What's the real world cost of taking six
  190. 05:42months off because you can't access it?
  191. 05:44Y
  192. 05:44there's a shortage and maybe better
  193. 05:46drugs will come along. Like I don't
  194. 05:47necessarily have a problem with it.
  195. 05:48Although if you talk to type 1 diabetics
  196. 05:50in the old days, they weren't crazy
  197. 05:52about the idea that they had to
  198. 05:53constantly inject themselves with
  199. 05:54insulin. Now there are better better
  200. 05:55delivery devices. I kind of feel like
  201. 05:57eventually there'll be some slowrelease
  202. 06:00um polymer that will just kind of give
  203. 06:02you a micro dose of it. You could dial
  204. 06:04it up if you want.
  205. 06:05Those are all pills. Now
  206. 06:06personally I don't worry so much about
  207. 06:07like for the rest of your life. I worry

  208. Neurological Impact & Learning

  209. 06:09more about the much shorter life if
  210. 06:11people are obese. But what about these
  211. 06:13brain effects? I I do worry about a
  212. 06:15brain that's developing in the context
  213. 06:17of of a you know thousandfold or more
  214. 06:20increase in these GLPs because when we
  215. 06:22had um Zach Knight on the podcast, he's
  216. 06:24not a clinician, he's a scientist up at
  217. 06:26UCSF, Howard Hughes investigator, which
  218. 06:27means he's like a superstar and deserves
  219. 06:30to be in that category. He described
  220. 06:32that the diabetic drugs would increase
  221. 06:34GLP by like like double quadruple, but
  222. 06:37the weight loss effects weren't really
  223. 06:39there. But the drugs that you rattled
  224. 06:41off a few minutes ago, Monaro, Zmpic,
  225. 06:43etc. And certainly Redat True Tide.
  226. 06:45We're talking about thousandfold
  227. 06:47increases in GPS, we don't know what the
  228. 06:49long-term effects of those are on like
  229. 06:50neuroplasticity and learning. Could be
  230. 06:52great. Yes.
  231. 06:52Could be positive. We shouldn't always
  232. 06:53assume those effects are bad. Yeah. Like
  233. 06:55the effects for like let's say a
  234. 06:5760-year-old pre-diabetic diabetic on
  235. 06:59Alzheimer's disease seems to be
  236. 07:01potentially positive. I think the the
  237. 07:03study last year didn't show a good
  238. 07:04signal on our Alzheimer's prevention,
  239. 07:06but we know diabetes and cardio
  240. 07:08metabolic disease speeds up that
  241. 07:09transition. So controlling insulin
  242. 07:11dynamics might be beneficial there and
  243. 07:13the obesity is not great for for
  244. 07:15Alzheimer's risk. The question is what
  245. 07:16about for like these cognitive effects?
  246. 07:18Is the effect happening from the drug
  247. 07:20itself? Is it from misuse of the drug?
  248. 07:22Too too high of a dose. You're not
  249. 07:23getting enough electrolytes. You're not
  250. 07:24getting enough micronutrients,
  251. 07:26macronutrients, you know, your blood
  252. 07:28sugar is low. Because a lot of these
  253. 07:29patients, the way we we approach it is
  254. 07:32training wheel effect when it comes to
  255. 07:33GLP-p1s. Like, hey, you come to us,

  256. Clinical Protocols & Side Effects

  257. 07:35you're a patient, you want to use GLP1s,
  258. 07:37we'll give you a lowest dose as possible
  259. 07:38that has an effect for you, GLP-1 in
  260. 07:41conjunction with lifestyle modification,
  261. 07:43dietary advice, exercise programs, etc.,
  262. 07:45etc., and then hopefully peel away those
  263. 07:47those training wheels or keep them on if
  264. 07:49you need them until we get to the end
  265. 07:51point that we want. Now, when people do
  266. 07:54it that way, I don't hear a lot of these
  267. 07:55effects anecdotally from from work
  268. 07:57[clears throat] patients that we hear
  269. 07:58about online where people are like, "Oh,
  270. 08:00I'm depressed. I hate my life from from
  271. 08:02these drugs." And the question is, are
  272. 08:04they just, you know, a lot of people
  273. 08:05have low blood pressure from from these
  274. 08:07drugs because they're not, you know,
  275. 08:08consuming enough electrolytes or enough
  276. 08:10food period?
  277. 08:11Cuz like some people will take a mega
  278. 08:13dose of these drugs and end up not
  279. 08:14eating like a day goes by, they've eaten
  280. 08:18one meal. That's not conducive to to
  281. 08:20good feeling good. everyone, you know,
  282. 08:22the reason people are eating in the
  283. 08:22first place is because eating is is such
  284. 08:24a pleasurable experience for humans and
  285. 08:25a social experience, etc., etc. The
  286. 08:27other thing is if you're not eating with
  287. 08:28people on the same table, are you having
  288. 08:30less of that socialization aspect? A lot
  289. 08:32of times you meet up to eat or drink or
  290. 08:34whatever it may be. So I'm very curious
  291. 08:36when it comes to the cognitive effects,
  292. 08:37is it from the drug directly interacting
  293. 08:39with receptors in the brain when we
  294. 08:41we've seen that the right amount of dose
  295. 08:43decreases inflammation in the brain or
  296. 08:44is it because of the social aspects of
  297. 08:46the drug changing the way you behave and
  298. 08:48therefore leading to negative out? dare
  299. 08:50you think of confounding variables.
  300. 08:52[laughter] It's like, no, it's so cool
  301. 08:53cuz you're willing to go outside the box
  302. 08:55and say, hey, listen, this might be due
  303. 08:57to some of the um downstream
  304. 08:59consequences of of reduced appetite.
  305. 09:01Yeah. And we know the literature shows
  306. 09:02that people now are having less alcohol
  307. 09:04cravings from this. It might be changing

  308. Dopamine Signaling and Stacking

  309. 09:06the way the dopanergic signaling is
  310. 09:08happening in the brain, which is
  311. 09:09concerning, right? Because a lot of
  312. 09:11people will be stacking this with, you
  313. 09:12know, ADHD medications. Uh they might be
  314. 09:15using some of these peptide stimulants,
  315. 09:16um smack link, whatever it may be. So
  316. 09:18the question because what happens is
  317. 09:19people go to these websites, they they
  318. 09:20buy one more peptide and they got a
  319. 09:22great result and they'll be like, you
  320. 09:23know, let me add three more peptides on
  321. 09:24peptides.
  322. 09:25Yes, it's a increasing AOV problem. So
  323. 09:27the average sale value goes up
  324. 09:30from these sites.
  325. 09:32We'll see where where GLP ones go. The
  326. 09:34the the reality is it's here. There
  327. 09:35there is no pre GLP1 world for us as
  328. 09:38clinicians, as health enthusiasts. We're
  329. 09:40in a postGP1 world and everything kind
  330. 09:42of dictates downstream from that. The
  331. 09:45people I know who've taken um these and
  332. 09:47I don't know exactly which are taking
  333. 09:48much lower dosages than were prescribed
  334. 09:50to them and they are indeed sharing them
  335. 09:52with getting the prescription than
  336. 09:54people are sharing them. People are cost
  337. 09:56sharing now people are trying to get
  338. 09:58them from other sources. Several of
  339. 10:00those people say they they feel like
  340. 10:01they can think better. But I told them,
  341. 10:03well yeah, if your insulin sensitivity
  342. 10:04is improved,
  343. 10:06if you're carrying less body fat, body
  344. 10:07fat's an endocrine organ. It's you know
  345. 10:09you need some body fat. But
  346. 10:11there could be a number of reasons for
  347. 10:12that. I don't know if these are direct
  348. 10:13effects on the brain.
  349. 10:14Yeah. Well, I mean, leptin sensitivity

  350. Fertility & Ozempic Babies

  351. 10:16increases as you decrease the body fat
  352. 10:17mass. There's there's GP1 receptors on
  353. 10:19the pomcy neurons in the brain and no
  354. 10:21one's kind of examined what that means
  355. 10:23downstream for the leptin melano leptin
  356. 10:25melanoin pathway and what that means for
  357. 10:27energy status, you know, thyroid hormone
  358. 10:29production, reproductive status. We know
  359. 10:31a lot of people are oyic babies in that
  360. 10:34a lady will will be subfertile or
  361. 10:36infertile, start a weight loss drug, and
  362. 10:39then find out by accident she's
  363. 10:40pregnant.
  364. 10:41Was she obese before? Yeah, there's
  365. 10:43these you're overweight, obese women
  366. 10:44that are having um their fertility
  367. 10:46improve as a result of losing the weight
  368. 10:47because we know
  369. 10:48uh your leptin status is a key driver of
  370. 10:50fertility because if if you're having
  371. 10:52low leptin levels, you're starving. You
  372. 10:53shouldn't be fertile. If you have too
  373. 10:54much leptin and you're leptin resistant,
  374. 10:57you shouldn't be having kids either. So,
  375. 10:59both of those those things kind of get
  376. 11:01modulated by these drugs as well.
  377. 11:03There was a science paper some years ago
  378. 11:04that leptin hitting a certain threshold
  379. 11:06is actually what signals the onset of
  380. 11:08puberty in females. Is that still
  381. 11:10considered true? I think that's that's
  382. 11:11that's part of it
  383. 11:12makes sense like enough body fat to
  384. 11:14signal that there are enough resources
  385. 11:15and then um animals or that was an
  386. 11:18animal study or the idea was that people
  387. 11:19perhaps also become females become
  388. 11:21reproductively competent at the point
  389. 11:23where there's enough energetic resources
  390. 11:24that interesting [music]