WEBVTT 1 00:00:11.560 --> 00:00:14.880 Hello, this is the Itchy and Bitchy Podcast because being 2 00:00:15.080 --> 00:00:19.640 itchy is bitchy and our medical system sucks. I'm doctor 3 00:00:19.719 --> 00:00:23.079 Keith Milica, a vetnary, allergist and dermatologist. 4 00:00:22.519 --> 00:00:25.399 And I'm Stephen Miller, a doctor of nursing practice and 5 00:00:25.480 --> 00:00:27.039 a Q Care nurse practitioner. 6 00:00:27.399 --> 00:00:31.519 Send us your questions at ask at itch not dot com. 7 00:00:32.200 --> 00:00:34.640 We love you, but we're not your doctors. The information 8 00:00:34.759 --> 00:00:38.520 we discuss is not direct medical advice. Please talk to 9 00:00:38.560 --> 00:00:42.520 your provider who is the expert on your care. The 10 00:00:42.560 --> 00:00:46.240 Itchy and BITCHI podcast is sponsored by doc Itchy Medical 11 00:00:46.280 --> 00:00:49.799 Pets supplements designed to optimize your pets health with the 12 00:00:49.880 --> 00:00:54.920 latest veterinary medical research. Visit docichi dot com or find 13 00:00:55.000 --> 00:00:58.600 us on Amazon and please click that follow button and 14 00:00:58.679 --> 00:01:06.359 send us a question at a at itchno dot com. Thanks, hello, 15 00:01:06.959 --> 00:01:08.640 doctor Miller, how's it going. 16 00:01:08.879 --> 00:01:12.599 Hi? Welcome to all of our listeners. I'm so glad 17 00:01:12.599 --> 00:01:13.439 we're back together. 18 00:01:13.920 --> 00:01:17.239 Yes, and we're now posting on Mondays, so look for 19 00:01:17.280 --> 00:01:19.159 the uploads on Monday morning. 20 00:01:19.079 --> 00:01:21.840 And we hope that you will go on our Facebook 21 00:01:21.920 --> 00:01:25.239 site which I and B Podcast. 22 00:01:24.840 --> 00:01:27.959 And send us a question that ask at itch not 23 00:01:28.159 --> 00:01:30.200 dot com Okay, so. 24 00:01:30.560 --> 00:01:31.200 Are you ready? 25 00:01:31.359 --> 00:01:33.359 Yeah, Okay, this is going to be a whirlwind because 26 00:01:33.400 --> 00:01:37.439 this is the craziest, most amazing thing I can think of. 27 00:01:38.239 --> 00:01:41.920 There are three major events that I know of in 28 00:01:41.959 --> 00:01:46.480 my lifetime sort of in my lifetime that absolutely revolutionized 29 00:01:46.760 --> 00:01:48.359 medicine as we know. 30 00:01:48.439 --> 00:01:50.840 It just totally changed the human species. 31 00:01:51.120 --> 00:01:53.480 Detail it soundsl. 32 00:01:53.079 --> 00:01:56.799 So the first is antabotics. What have antibotics done for humans? 33 00:01:56.840 --> 00:02:06.079 Doctor Miller cured like death, repentuated eighty percent society, So antibotics. 34 00:02:06.239 --> 00:02:11.199 The second most tragic, crazy thing that happened total misadventure 35 00:02:11.360 --> 00:02:14.080 is the lidamide. So this was in the nineteen fifties 36 00:02:14.080 --> 00:02:17.719 and sixties during the valium culture. Mother's Little Helper, make 37 00:02:17.800 --> 00:02:22.719 you happy, and so thalidamide was an anti vomit morning 38 00:02:22.759 --> 00:02:27.599 sickness drug and it turned out to cause horrible birth defects. 39 00:02:27.960 --> 00:02:31.319 Luckily our FDA, which some people don't like very much, 40 00:02:31.360 --> 00:02:34.120 but they did not approve in the United States, so 41 00:02:34.560 --> 00:02:38.639 a lot of American babies were spared from the limb deformities. 42 00:02:39.000 --> 00:02:42.240 But thalidamide was this amazing feel good drug in the 43 00:02:42.240 --> 00:02:46.680 fifties and sixties for pregnant women, but caused horrible birth 44 00:02:46.719 --> 00:02:51.599 defects and a whole generation of birth defects. So horrible, 45 00:02:51.639 --> 00:02:57.240 horrible misadventure. But what's crazy amazing, like the best of 46 00:02:57.319 --> 00:03:01.080 times the worst of times, is this gel one revolution. 47 00:03:01.759 --> 00:03:05.719 And I have not seen any other drug or treatment 48 00:03:05.840 --> 00:03:10.000 that falls into this kind of crazy madness of exploration 49 00:03:10.879 --> 00:03:13.639 and benefits. And so we're going to talk about GLP 50 00:03:13.759 --> 00:03:18.719 ones again. This is an updated version. Karen Nicol did 51 00:03:18.759 --> 00:03:22.319 a really good episode previously, check that out if you 52 00:03:22.360 --> 00:03:27.719 would like. But things have changed in months, definitely within 53 00:03:27.719 --> 00:03:31.159 the last year. But every week there's new and new things. 54 00:03:31.240 --> 00:03:33.680 So we're going to divide this episode into sort of 55 00:03:33.680 --> 00:03:37.560 an introduction and then what GLP ones are actually approved 56 00:03:37.680 --> 00:03:40.520 for and how that sort of got started, and then 57 00:03:40.520 --> 00:03:42.400 we're going to take a break and come back and 58 00:03:42.439 --> 00:03:46.080 talk about all of the possibilities and the proposed mechanisms. 59 00:03:46.400 --> 00:03:48.879 A lot of them are thought of and sort of 60 00:03:49.240 --> 00:03:53.439 hinted at by response to therapy, but not documented in 61 00:03:53.560 --> 00:03:58.000 really good clinical statistical trials. And then we're going to 62 00:03:58.319 --> 00:04:01.240 have a last segment of the possible side effects, which 63 00:04:01.360 --> 00:04:05.280 are kind of interesting when you start thinking about mechanisms 64 00:04:05.639 --> 00:04:07.759 of how the GLP actually works. 65 00:04:07.960 --> 00:04:11.199 And for our listeners, that don't know. What GLP one 66 00:04:11.400 --> 00:04:17.360 receptor agonists are is glucagon like peptide receptor agonists, and 67 00:04:17.439 --> 00:04:23.160 so these offer all kinds of benefits for metabolic, cardiovascular, renal, 68 00:04:23.240 --> 00:04:26.040 and weight related benefits. So we'll we'll dive in. 69 00:04:26.279 --> 00:04:29.920 Yeah, so glucagon is produced in the liver, and agonist 70 00:04:30.040 --> 00:04:33.040 means that we're going to stimulate the receptors and so 71 00:04:33.240 --> 00:04:36.279 molecularly that's how these things work. 72 00:04:36.720 --> 00:04:38.399 And so we started off. 73 00:04:38.759 --> 00:04:41.040 Do you remember when they first got approved three years 74 00:04:41.040 --> 00:04:42.360 ago maybe four? 75 00:04:42.839 --> 00:04:44.000 Yeah, so so. 76 00:04:44.079 --> 00:04:46.319 Not that long ago in the grand scheme of things, 77 00:04:46.600 --> 00:04:49.319 and they were first approved. You remember the first drug 78 00:04:49.360 --> 00:04:50.000 that was approved. 79 00:04:50.199 --> 00:04:53.319 The first one was sex Sinda and. 80 00:04:53.319 --> 00:04:57.360 It was approved for weight loss. Weight lossbetes that. 81 00:04:57.680 --> 00:04:59.720 They are a glue tide. It was indicated for what 82 00:04:59.759 --> 00:05:05.680 loss Victosa, which was the branded other version. With all 83 00:05:05.720 --> 00:05:08.720 of these classes, they get branded in different ways, and 84 00:05:08.759 --> 00:05:11.480 so the branding of Victosa was to decrease cardio event 85 00:05:12.079 --> 00:05:18.639 cardiovascular event reduction in patients with diabetes and established cardiovascular disease. 86 00:05:18.759 --> 00:05:22.800 So very specific prescribing guidelines, and so I would bet 87 00:05:22.839 --> 00:05:24.920 that when it first came out, you didn't really prescribe 88 00:05:24.920 --> 00:05:27.079 it to a huge number of patients. 89 00:05:27.040 --> 00:05:31.399 On the cardiology side. We didn't dive in initially. 90 00:05:31.519 --> 00:05:34.879 That's accurate, okay, So and this is just kind of 91 00:05:34.920 --> 00:05:37.000 back up a step, and then we're going to take 92 00:05:37.000 --> 00:05:39.759 a short break and come back with more detail. But 93 00:05:39.920 --> 00:05:42.800 to back up a step, this is one of the peptides. 94 00:05:42.839 --> 00:05:46.560 And peptides are all trendy now, but you need to 95 00:05:46.639 --> 00:05:49.680 kind of understand what peptides are. They're simply proteins that 96 00:05:49.720 --> 00:05:52.959 are found in the human body and interesting like other 97 00:05:53.120 --> 00:05:57.560 drugs that are patented and drug companies like Pfizer or 98 00:05:57.639 --> 00:06:01.639 Eli Lilly can have a patent on it. The Supreme 99 00:06:01.680 --> 00:06:05.199 Court decided that these peptides are human proteins because they're 100 00:06:05.279 --> 00:06:10.279 part of the human normal anatomy system, that they're not patentable. 101 00:06:10.399 --> 00:06:14.279 So these peptides are very specific and they have pros 102 00:06:14.319 --> 00:06:17.600 and cons They have benefits and side effects depending on 103 00:06:17.680 --> 00:06:20.439 exactly what the peptide is and what it does. So 104 00:06:20.519 --> 00:06:22.399 we're going to take a short break here and then 105 00:06:22.399 --> 00:06:26.439 we're going to come back and talk about the proposed 106 00:06:26.720 --> 00:06:32.560 and approved guidelines and treatment possibilities for these glp ones. 107 00:06:32.600 --> 00:06:33.240 Stick with us. 108 00:06:33.519 --> 00:06:37.759 It gets really interesting and really crazy from here. It's 109 00:06:37.759 --> 00:06:41.040 magical medicine moments. So hang with us. 110 00:06:52.240 --> 00:06:55.360 All right, we're back. I hope he stayed with us. 111 00:06:55.759 --> 00:06:57.439 So now we're going to talk about all of the 112 00:06:57.480 --> 00:07:03.079 different proposed treatments and treatments for these GLP ones and 113 00:07:03.720 --> 00:07:07.120 it gets it gets really interesting. So just as crazy 114 00:07:07.560 --> 00:07:11.839 as antibotics and pholidamide, where these GLP one started off 115 00:07:11.879 --> 00:07:15.319 with this little bitty niche kind of treatment protocol and 116 00:07:15.399 --> 00:07:19.079 now it is just crazy what they're showing to have 117 00:07:19.120 --> 00:07:24.839 benefits for. So from the data side of things, Stephen, 118 00:07:24.920 --> 00:07:27.600 what what are they actually used for and prescribed for? 119 00:07:27.839 --> 00:07:28.279 Right now? 120 00:07:28.519 --> 00:07:31.160 Yeah, so follow me into the weeds a moment. 121 00:07:31.600 --> 00:07:33.959 Yes, I like weeds. Yeah, data is good, give me 122 00:07:34.000 --> 00:07:34.560 a good action. 123 00:07:34.600 --> 00:07:38.040 And so initially we talked about sex and and nick tosa, 124 00:07:38.120 --> 00:07:42.240 and then the next generation was seema glue tide, which 125 00:07:43.360 --> 00:07:49.399 was ozimpic, and then Rightbelsa's and we go by and 126 00:07:49.439 --> 00:07:53.879 they're all it's interesting how as they've been branded, they 127 00:07:54.120 --> 00:07:58.480 the branding has has been approved for certain different indications. 128 00:07:58.920 --> 00:08:01.959 And so this is why people will meet barriers at 129 00:08:01.959 --> 00:08:04.920 the pharmacy counter if the drugs not written under the 130 00:08:05.040 --> 00:08:09.240 certain indication that it's approved for. And so for example, 131 00:08:09.279 --> 00:08:13.759 we go V is for weight management and obesity with 132 00:08:13.879 --> 00:08:18.279 weight related comorbidities, which is kind of a broad label and. 133 00:08:18.199 --> 00:08:22.240 That could be anything from diabetes, pre diabetes, even cancer 134 00:08:22.360 --> 00:08:23.519 is related to abusie. 135 00:08:23.680 --> 00:08:28.800 It is also indicated for cardiovascular event reduction and obese 136 00:08:28.839 --> 00:08:34.320 patients with established cardiovascular disease, so anybody with atherosclerosis. And 137 00:08:34.360 --> 00:08:39.320 then it is also indicated for metabolic dysfunction with fatty 138 00:08:39.360 --> 00:08:43.720 liver disease, specifically looking more into fibrosis of the liver. 139 00:08:43.879 --> 00:08:47.879 So glucagon is liver produced and so that's where this 140 00:08:48.000 --> 00:08:49.759 whole mechanism kind of. 141 00:08:51.279 --> 00:08:54.519 Resides in the body. So how do they so all 142 00:08:54.559 --> 00:08:57.720 of these peptides are similar in cross reaction. 143 00:08:57.879 --> 00:09:02.200 Yeah, so it wasn't done because they have to give indications. 144 00:09:01.320 --> 00:09:05.080 Right, but do the pharmacist and the providers if so, 145 00:09:05.159 --> 00:09:08.159 if they have a lot of overlap, but are they prescribing? 146 00:09:08.919 --> 00:09:12.440 You want you want treatment A, and so you do 147 00:09:12.600 --> 00:09:14.759 drug A, and you want treatment B, so you do 148 00:09:14.879 --> 00:09:17.320 drug B even though both drugs will do A. 149 00:09:17.559 --> 00:09:18.120 That's great. 150 00:09:18.480 --> 00:09:24.080 And so in the clinical setting, if you are prescribing, 151 00:09:24.519 --> 00:09:30.320 say for example, you're prescribing zep bound, which is tears 152 00:09:30.360 --> 00:09:34.279 zeppatide and it's approved for chronic weight management and obstructive 153 00:09:34.360 --> 00:09:39.399 sleep apnea. And if the patient doesn't have those disease processes, 154 00:09:40.120 --> 00:09:44.480 but yet they may have cardiovascular disease, then they would 155 00:09:44.480 --> 00:09:47.879 be covered for we go Vy, which has the cardiovascular indication. 156 00:09:48.000 --> 00:09:50.720 So that becomes an insurance paperwork kind of thing. But 157 00:09:50.919 --> 00:09:53.480 as far as the drug is actually the mechanism of action, 158 00:09:53.600 --> 00:09:56.639 does it really matter which one tick and then some 159 00:09:56.759 --> 00:09:59.480 maybe once you're next summer, once a day. They now 160 00:09:59.519 --> 00:10:02.720 have oral drugs because it's much cheaper and easier to administer, 161 00:10:03.000 --> 00:10:05.759 so their injecting devices are actually quite expensive. 162 00:10:06.000 --> 00:10:09.159 Yeah, so there's oral we go Vi, which is now available. 163 00:10:09.200 --> 00:10:15.039 There's Rybelsis, which is semaglutide as well, and it has 164 00:10:15.080 --> 00:10:18.759 the indications for diabetes cardiovasco or men reduction in patients 165 00:10:18.759 --> 00:10:20.360 with type two diabetes melitis. 166 00:10:20.399 --> 00:10:22.799 So we're kind of in this situation where we have 167 00:10:22.879 --> 00:10:27.039 lots of different drugs and the paperwork kind of regulates 168 00:10:27.080 --> 00:10:31.440 which drug gets which diagnosis and which treatment, but in reality, 169 00:10:31.679 --> 00:10:34.559 all of the drugs kind of do similar things and 170 00:10:34.600 --> 00:10:37.720 they have an expanding list of benefits. 171 00:10:37.879 --> 00:10:41.360 Yeah, so patients just need to discuss this with their 172 00:10:41.519 --> 00:10:45.519 prescribing provider to make sure that whatever drug is written 173 00:10:45.799 --> 00:10:49.120 is written under the labeling that's appropriate. 174 00:10:49.679 --> 00:10:51.639 Okay, otherwise you're going to get pushed back from your 175 00:10:51.639 --> 00:10:52.440 insurance company. 176 00:10:52.480 --> 00:10:54.320 That's right. So I'm going to. 177 00:10:54.240 --> 00:10:58.600 Read a list of all of the proposed theoretical benefits 178 00:10:58.639 --> 00:11:01.519 that may or may not have been proven with really 179 00:11:01.559 --> 00:11:05.799 good statistical studies based on tens of thousands of people. 180 00:11:06.080 --> 00:11:09.200 But I want you first to tell me what the 181 00:11:09.360 --> 00:11:11.559 actual approved indications are. 182 00:11:11.840 --> 00:11:17.639 So really you want to break the benefits down into 183 00:11:18.399 --> 00:11:22.639 three major categories, or four major categories. One is glycemic. 184 00:11:22.000 --> 00:11:24.440 Control, which is sugar dibe. 185 00:11:24.240 --> 00:11:28.159 Like glucose, and the other is weight loss, The other 186 00:11:28.360 --> 00:11:35.279 is cardiovascular benefits, and then of course renal protection, and 187 00:11:35.320 --> 00:11:39.559 then I left off one, which is the fatty liver indication. 188 00:11:40.000 --> 00:11:43.679 Okay, So those are the indications. But what gets really 189 00:11:43.759 --> 00:11:47.120 crazy and why this drug is so amazing is that 190 00:11:47.159 --> 00:11:51.759 it's one of the moments in medicine where the expected 191 00:11:51.840 --> 00:11:57.039 benefits were fairly narrow and limited, and then what the 192 00:11:57.120 --> 00:12:02.799 patients are actually experiencing has just exponentially exploded. So under 193 00:12:02.840 --> 00:12:06.559 weight loss, for instance, your joints get better. Under weight loss, 194 00:12:06.600 --> 00:12:12.000 your libido gets better. So it's just this crazy exponential, 195 00:12:12.559 --> 00:12:17.799 expansive list of benefits that these drugs have, even into depression, anxiety, 196 00:12:18.039 --> 00:12:18.720 drug addiction. 197 00:12:18.960 --> 00:12:22.200 So on my end, I really pitt because I'm work 198 00:12:22.519 --> 00:12:28.039 in cardiology. You look at just so, cardiovascular death as 199 00:12:28.080 --> 00:12:31.159 the number one leading cause of death in the United States, right, 200 00:12:31.519 --> 00:12:36.120 So they did this meta analysis, which was ten clinical 201 00:12:36.159 --> 00:12:39.759 trials looking at seventy three hundred and fifty one patients. 202 00:12:39.759 --> 00:12:43.200 That's a huge number of patients. And so major adverse 203 00:12:43.240 --> 00:12:47.279 cardiovascular events such as stroke, cardiovascular death, and non fatal 204 00:12:47.360 --> 00:12:52.519 am I were reduced by fourteen percent, heart failure hospitalizations 205 00:12:52.559 --> 00:12:56.679 were reduced by fourteen percent, and then all cause mortality 206 00:12:56.720 --> 00:12:59.960 for dying from anything was reduced by about twelve percent. 207 00:13:00.200 --> 00:13:04.600 So just looking at the one indicated group, the major 208 00:13:04.960 --> 00:13:08.879 reductions in depth are impressive with this drug class. 209 00:13:09.000 --> 00:13:12.200 Yeah, and anything above ten percent is really pretty significant. 210 00:13:12.240 --> 00:13:14.120 So Okay, we're going to take a short break and 211 00:13:14.120 --> 00:13:16.279 then we're going to come back and talk about the 212 00:13:16.480 --> 00:13:19.480 other benefits. So if they look at these studies and 213 00:13:19.480 --> 00:13:21.320 they're more and more of them, So we have now 214 00:13:21.440 --> 00:13:25.320 hundreds of thousands of patients globally that are on these medications, 215 00:13:25.759 --> 00:13:27.879 and what they do is they say, well, what else 216 00:13:27.960 --> 00:13:31.399 is happening in these groups of patients? So anything above 217 00:13:31.440 --> 00:13:33.919 ten percent is really impressive. But when we come back, 218 00:13:33.960 --> 00:13:37.440 we're going to talk about some of these unexpected things, 219 00:13:37.480 --> 00:13:40.440 like a thirty percent reduction in cancer risk. 220 00:13:40.519 --> 00:13:42.759 And I think it's really really important for our listeners 221 00:13:42.799 --> 00:13:47.279 to understand that when we're looking at some of these benefits, 222 00:13:47.600 --> 00:13:50.720 that most of those things are coming out of subgroup 223 00:13:50.759 --> 00:13:53.039 analysis from these studies. So it may not be the 224 00:13:53.080 --> 00:13:56.879 indication for the drug, but certainly benefit was seen and. 225 00:13:56.799 --> 00:13:59.240 More evidence is needed before it's a proven So we 226 00:13:59.279 --> 00:14:02.279 have correlation but not causation yet. Okay, we're going to 227 00:14:02.320 --> 00:14:03.600 take a break and then we're going to come back 228 00:14:03.639 --> 00:14:07.799 and talk about these kind of amazingly weird, crazy things 229 00:14:07.799 --> 00:14:11.879 that this drug therapies can do. Okay, hang tight and 230 00:14:12.000 --> 00:14:27.519 join us on the other side. Hey, I hope you 231 00:14:27.559 --> 00:14:28.399 made it back with us. 232 00:14:28.840 --> 00:14:30.159 So what we're going to do is I'm going. 233 00:14:30.080 --> 00:14:32.639 To read a list of all of the proposed benefits 234 00:14:32.679 --> 00:14:35.360 and doctor Miller here is going to chime in with 235 00:14:35.399 --> 00:14:40.440 some data if he has any kind of opinion about it. 236 00:14:40.480 --> 00:14:43.399 So I looked up on Claude. Actually is what I've 237 00:14:43.399 --> 00:14:46.759 switched to you now from chat, and I came up 238 00:14:46.759 --> 00:14:51.799 with sixty five different proposed benefits of GLP one and 239 00:14:51.840 --> 00:14:57.080 they're grouped into kind of specific organ systems. So cardiovascular 240 00:14:57.600 --> 00:15:00.000 benefits are pretty well done. 241 00:15:00.080 --> 00:15:02.080 So we already yeah, we already touched on. 242 00:15:02.080 --> 00:15:05.279 That, and that's that's even down to like reduced hospitalization 243 00:15:05.440 --> 00:15:10.759 visits associated reduced hypertension, and then metabolic benefits, which are 244 00:15:11.200 --> 00:15:13.399 global and these are going to be related to weight 245 00:15:13.480 --> 00:15:17.600 loss and sugar insulin diabetes, and when you start affecting 246 00:15:17.799 --> 00:15:21.919 in a beneficial manner, that whole pathway, it pretty much 247 00:15:21.960 --> 00:15:27.200 relates to everything else. It relates to sex, drive, to joints, exercise, 248 00:15:28.360 --> 00:15:32.679 just pretty much whole morbidity, which is your overall disease. 249 00:15:34.279 --> 00:15:39.240 Accumulation is improved. Hepatic disease. So you mentioned fatty liver disease, 250 00:15:39.440 --> 00:15:42.360 but actually liver enzymes will go down, so if you 251 00:15:42.399 --> 00:15:46.000 have any kind of associated with liver issues. 252 00:15:45.799 --> 00:15:48.759 And the day Lily is strong on that in that 253 00:15:49.000 --> 00:15:53.960 the indication for these drugs is there for fatty liver disease. 254 00:15:54.159 --> 00:15:57.759 You skipped over the whole renal I'm. 255 00:15:57.600 --> 00:16:00.559 Getting there, okay, yeah, okay, So and we'll come back 256 00:16:00.559 --> 00:16:03.799 to renal disease. So you know, kidneys, Like, who would 257 00:16:03.799 --> 00:16:06.519 think that kidneys are I wouldn't think that kidneys are 258 00:16:06.559 --> 00:16:10.039 associated with like weight loss drug But so how are 259 00:16:10.080 --> 00:16:10.919 kidneys benefited? 260 00:16:11.120 --> 00:16:14.440 Yeah, so GLP one a's decreased micro albumin area or 261 00:16:14.519 --> 00:16:19.320 albuminary and slow EGFR decline. There's a particular study called 262 00:16:19.320 --> 00:16:22.759 the Flow trial which looked at semaglue tide and it 263 00:16:22.840 --> 00:16:26.679 showed there was a twenty four percent reduction in kidney 264 00:16:26.720 --> 00:16:30.480 outcomes such as EGF to our decline, kidney failure, and 265 00:16:30.639 --> 00:16:35.080 kidney slash cardiovascular death. So pretty four percent. 266 00:16:35.360 --> 00:16:38.519 So he said a lot of that's really he works there. Yeah, 267 00:16:38.519 --> 00:16:41.679 anything about ten percent is impressive. So what he's basically 268 00:16:41.720 --> 00:16:44.960 talking about is how well the kidney processes fluids and 269 00:16:45.080 --> 00:16:51.679 toxins and GFR is glomyl glomerular filtration rates, and that's 270 00:16:51.759 --> 00:16:53.919 kind of what the kidney does, It filters out. 271 00:16:54.320 --> 00:16:56.159 And there was a meta analysis, by the way of 272 00:16:56.200 --> 00:16:59.399 all of that data, which is a huge It still 273 00:17:00.279 --> 00:17:04.720 seventeen percent reduction and composite kidney outcomes across the class. 274 00:17:04.839 --> 00:17:07.359 So that's a fairly impressive. 275 00:17:07.039 --> 00:17:10.160 And who would have thought kidneys so neurologic disorder, so 276 00:17:10.680 --> 00:17:13.720 alcoholism and liver disease. That kind of makes sense that 277 00:17:13.759 --> 00:17:17.000 if you're improving liver function, that doesn't mean We were 278 00:17:17.000 --> 00:17:19.400 talking with our friends last night who are into all 279 00:17:19.440 --> 00:17:22.920 of these vitamin supplements to improve their health, and I 280 00:17:23.000 --> 00:17:25.200 pointed out that the biggest improvement would be to stop 281 00:17:25.279 --> 00:17:27.440 drinking alcohol, which is a neurotoxin. 282 00:17:27.680 --> 00:17:30.079 YEA, So I will point out to our audience that 283 00:17:30.200 --> 00:17:34.599 they're yes in the subgroup analysis there, which means not 284 00:17:35.519 --> 00:17:38.319 the primary outcome for the trial, but they broke down 285 00:17:38.359 --> 00:17:41.279 the subgroups and they looked at people's alcohol intake, and 286 00:17:41.720 --> 00:17:46.160 early signals were found for reducing alcohol and substance use, 287 00:17:46.200 --> 00:17:50.440 although this is not totally clear and needs further investigation. 288 00:17:50.640 --> 00:17:52.960 So I was talking about liver health and the effect 289 00:17:53.000 --> 00:17:56.559 of the toxic alcohol, and we're recording this as we're 290 00:17:56.599 --> 00:17:58.599 having a glass of wine, so we definitely are not 291 00:17:58.839 --> 00:18:02.799 anti alcohol, but so the liver health benefits. But you're 292 00:18:02.799 --> 00:18:05.960 actually talking about behavior and addiction. So the amount of 293 00:18:06.000 --> 00:18:09.559 alcohol consumed, and this also happens with weight, that the 294 00:18:10.039 --> 00:18:15.640 food drive, the annoying, obsessive, compulsive food thoughts get reduced, 295 00:18:15.640 --> 00:18:17.480 and this is a huge impact on addiction. 296 00:18:17.640 --> 00:18:21.359 Yeah, the central nervous system effects are not clearly understood 297 00:18:21.480 --> 00:18:23.720 yet and so certainly need further investigation. 298 00:18:23.880 --> 00:18:28.960 Yeah, but the benefits for addictive behaviors, even shopping addiction, 299 00:18:29.200 --> 00:18:33.279 porn addiction, There are all of these sort of hints 300 00:18:33.319 --> 00:18:35.119 that these drugs may be beneficial. 301 00:18:35.240 --> 00:18:37.920 So again in the subgroups where we looked at trends 302 00:18:37.960 --> 00:18:41.200 on the forest plots, we saw that the data trended 303 00:18:41.240 --> 00:18:44.640 toward the SGLT two our GLP one. 304 00:18:44.519 --> 00:18:48.559 A yeah crazy, so okay, And what about Alzheimer's. 305 00:18:48.720 --> 00:18:54.279 So neuro degenerative disease. The preliminary evidence suggests some potential 306 00:18:54.319 --> 00:19:00.480 benefits in preventing dimension improving Parkinson's disease. Again, these are 307 00:19:00.559 --> 00:19:05.200 investigational poorly understood, but when you looked at subgroups, certainly 308 00:19:05.400 --> 00:19:08.839 there was some indication that this needed to be evaluated further. 309 00:19:09.759 --> 00:19:11.319 Do we have a proposed mechanism? 310 00:19:11.400 --> 00:19:11.559 Is it? 311 00:19:11.880 --> 00:19:12.200 We don't. 312 00:19:12.839 --> 00:19:15.640 Again, the whole central nervous system impact of this class 313 00:19:15.720 --> 00:19:16.640 is poorly understood. 314 00:19:17.200 --> 00:19:19.079 And this is just what blows my mind is that 315 00:19:19.319 --> 00:19:23.039 you know, this was launched for a very narrow, limited 316 00:19:23.799 --> 00:19:27.279 diagnosis set and just the potential impact. I mean, there 317 00:19:27.279 --> 00:19:30.759 are even discussions if you know entire populations. If every 318 00:19:30.799 --> 00:19:34.880 American citizen or Australian or Canadian should be put on 319 00:19:34.960 --> 00:19:39.599 these drugs just for overall health and well being, it's 320 00:19:39.720 --> 00:19:43.559 just amazing. So okay, respiratory impact. So you mentioned sleep apnea, 321 00:19:43.880 --> 00:19:46.279 So how is that benefit. 322 00:19:46.039 --> 00:19:50.680 Tears zeppetide is approved for obstructive sleep apnea? Is a 323 00:19:50.720 --> 00:19:54.039 web bound Well we don't know. Again, so there's the 324 00:19:54.039 --> 00:19:56.839 whole central nervous system piece that we don't understand. But 325 00:19:56.880 --> 00:20:01.160 then there's also that with obesity comes this pickwick in physiology, 326 00:20:01.200 --> 00:20:05.000 which is where the diaphragm so they really excurred and 327 00:20:05.079 --> 00:20:06.240 so then it's nine. 328 00:20:06.039 --> 00:20:09.599 Predominal fat and you just mechanically can't breathe. 329 00:20:09.920 --> 00:20:13.640 Yeah, So it's indicated for moderate to severe abstruct restrictive 330 00:20:13.680 --> 00:20:16.400 sleep apney and patient in adults with obesity. 331 00:20:16.680 --> 00:20:21.480 So even going to like arthritis and knee osteoarthritis and 332 00:20:21.559 --> 00:20:25.920 pain and cartilage degeneration. And that's probably related to weight 333 00:20:26.039 --> 00:20:29.680 that if you lose one hundred pounds with these drugs, 334 00:20:29.720 --> 00:20:32.319 then that's one hundred pounds less that your knees have 335 00:20:32.359 --> 00:20:32.880 to absorb. 336 00:20:33.039 --> 00:20:36.519 Yeah, So there is symptomatic improvement with this class in 337 00:20:37.839 --> 00:20:44.000 knee specifically knee osteoarthritis, and we think that is probably 338 00:20:44.039 --> 00:20:49.079 related to, you know, just the weight tension on the joint, 339 00:20:49.119 --> 00:20:50.240 although we just don't know. 340 00:20:50.519 --> 00:20:55.599 Okay, women's mental stricles become more stable and predictable and regulated. 341 00:20:55.640 --> 00:20:57.079 What the hell's up with that? 342 00:20:57.119 --> 00:21:00.000 Like, how does a weightless drug cause better menstrual suz. 343 00:21:00.000 --> 00:21:02.319 So if you just think about it, that is where 344 00:21:02.359 --> 00:21:05.920 hormones are stored, right, and so then you start reducing 345 00:21:06.720 --> 00:21:09.720 fatty tissue in central obesity, and then you start shifting 346 00:21:09.759 --> 00:21:14.319 hormones and so people do have some hormonal shift that occurs. 347 00:21:15.200 --> 00:21:17.160 Again, this just blows my mind. This is one of 348 00:21:17.200 --> 00:21:21.640 the most amazing things I've ever even contemplated. We talked 349 00:21:21.680 --> 00:21:26.160 about neurodegenerative diseases like Alzheimer's. 350 00:21:26.200 --> 00:21:28.680 What about stroke reduction? Is there any benefit for that? 351 00:21:29.599 --> 00:21:35.680 The drugs are indicated for cardiovascular event reduction, which includes stroke, 352 00:21:36.599 --> 00:21:40.880 so of all cardiovascular disease, so that's included there yet Okay. 353 00:21:41.039 --> 00:21:44.000 And then I've talked about my chronic migraines. This is 354 00:21:44.440 --> 00:21:47.519 researching this. I learned this that there's actually some evidence 355 00:21:47.599 --> 00:21:52.839 that migraines become less severe and less episodic, so fewer 356 00:21:52.920 --> 00:21:55.599 migraines per month on these trucks. 357 00:21:55.799 --> 00:21:59.400 Yeah, so this is evidence coming from the subgroup analysis 358 00:21:59.480 --> 00:22:05.039 and again poorly understood, not absolutely indicated, So make sure 359 00:22:05.039 --> 00:22:08.279 our audience understands that, but also knowing that there is 360 00:22:08.319 --> 00:22:12.519 some potential potential for improvement in those symptoms. 361 00:22:13.279 --> 00:22:17.119 Just so I've rethought starting to take these. I'm not 362 00:22:17.599 --> 00:22:20.759 terribly obese, and actually I'm very sensitive to the side effects, 363 00:22:21.279 --> 00:22:23.200 which we're going to cover in the next section. But 364 00:22:23.599 --> 00:22:27.640 I've actually restarted these for my migraines. I've had horribly 365 00:22:27.759 --> 00:22:34.319 uncontrolled migraines. Okay, so then what about reproductive benefits. We 366 00:22:34.400 --> 00:22:38.079 talked about the menstrual cycles that reproductive fertility seems to 367 00:22:38.119 --> 00:22:39.200 be increasing in this way. 368 00:22:39.279 --> 00:22:42.440 Yeah, so again, you know, you look at something when 369 00:22:42.519 --> 00:22:47.119 you look at a syndrome like PCOS polycystic ovarian syndrome, 370 00:22:47.160 --> 00:22:52.359 which can contribute to some infertility issues, and it's kind 371 00:22:52.400 --> 00:22:57.240 of a pre diabetic state and that impacts fertility. Again, 372 00:22:57.640 --> 00:23:02.119 fatty tissue stores hormones and shifts hormones, and so we 373 00:23:02.240 --> 00:23:06.799 just don't really know, but there is some some data 374 00:23:06.920 --> 00:23:09.440 and evidence in the subgroups to indicate there might be 375 00:23:09.480 --> 00:23:15.279 some benefit there. Just mind blowing, well, I think, yeah, 376 00:23:15.519 --> 00:23:20.359 so I think that they're at my pliants. So we 377 00:23:21.440 --> 00:23:25.720 in the US, all food is readily available everywhere. You 378 00:23:25.799 --> 00:23:27.839 drive down the highway and there are signs everywhere, and. 379 00:23:27.799 --> 00:23:29.519 We eat French fries for a week more. 380 00:23:29.599 --> 00:23:31.400 Then we go to a restaurant and we're served a 381 00:23:31.440 --> 00:23:36.920 three person portion and we continue to eat that way 382 00:23:37.039 --> 00:23:41.680 and our bodies can't, uh can't keep up, and so 383 00:23:41.839 --> 00:23:44.519 then there's this shifting of hormones that all of the 384 00:23:44.519 --> 00:23:52.799 obesity problem does impact neuroentocrine system, central nervous system, cardiovascular system. 385 00:23:53.160 --> 00:23:56.680 And so this impact is what we're trying to understand better. 386 00:23:56.759 --> 00:23:59.920 And then what actually stimulated us researching this and do 387 00:24:00.039 --> 00:24:03.400 in this episode was recent information that was just released 388 00:24:03.400 --> 00:24:08.119 on cancer rates. Yeah, so anything above ten percent is impressive, 389 00:24:08.240 --> 00:24:12.759 and the recent data looks at reduction in cancer all 390 00:24:12.799 --> 00:24:17.599 sorts of cancer, prostate, ovarian, breast cancer of twenty to 391 00:24:17.640 --> 00:24:18.319 thirty percent. 392 00:24:18.440 --> 00:24:23.480 So again, the latest information on this particular evidence is 393 00:24:23.519 --> 00:24:27.839 that we don't really know. An Umbrella review found no 394 00:24:27.880 --> 00:24:33.240 substantial association between GLP one ra's use and cancer risk 395 00:24:33.319 --> 00:24:41.079 across thyroid, pancreatic, and overall cancer outcomes. So we don't know, 396 00:24:41.519 --> 00:24:44.480 and I think it's important for people to really understand 397 00:24:44.720 --> 00:24:50.599 that in that certainly port eating can cause all kinds 398 00:24:50.599 --> 00:24:52.000 of GI cancers and this and that. 399 00:24:52.799 --> 00:24:55.279 So one of the reason he mentioned thiraid is one 400 00:24:55.319 --> 00:24:58.160 of the contraindications in the next section. We're going to 401 00:24:58.160 --> 00:25:00.559