by A/Prof Jon Segal and Dr James Haridy
“Two Guys Talking $#it” is a podcast where two Gastroenterologists break down complex topics into engaging, educational, and occasionally humorous conversations. From liver health to gut microbiota and everything in between, A/Professor Jonathan Segal and Dr James Haridy deliver insights, share the latest research, and discuss clinical pearls with the odd guest in tow. Comments, suggestions, questions please contact us on twitter @2guystalkingit or leave a comment below..
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12/18/2024
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August 9, 2026
<p>Professor Nick Talley has spent 35 years building the field of neurogastroenterology, and he'd like us all to stop saying "functional". He is one of the global top medical researchers, a distinguished Australian gastroenterologist, and educator known for his seminal work on neurogastrointestinal disorders and co-authoring classic clinical examination textbooks.</p><p></p><p>His argument is that the label sends patients and doctors looking in the wrong place. A lot of these people don't have a brain problem, they have a duodenal one, and he makes the case for a term he prefers: neurogastrointestinal disorder. From there he takes us through the pathophysiology his group has spent years building, subtle duodenal eosinophilia that ordinary pathologists aren't counting, an abnormal duodenal microbiome, and food antigens setting off an immune response that eventually becomes self-sustaining.</p><p></p><p>Then the practical stuff. Why he biopsies the duodenum, why he reaches for antihistamine blockade, why amitriptyline and not nortriptyline, when mirtazapine is the right call, and what he does when everything has failed. Plus when a gastric emptying study actually changes anything, why lactulose breath tests are not helpful, his approach to cyclic vomiting, and a reminder that rumination is not vomiting.</p><p></p><p><b>Keywords:</b> functional dyspepsia, DGBI, neurogastroenterology, duodenal eosinophilia, eosinophilic duodenitis, gastroparesis, Rome V, amitriptyline, microbiome, cyclic vomiting, SIBO, breath testing, Nick Talley</p><p></p><p>As always comments, questions, feedback and suggestions please send to: </p><p>X: @2guystalkingit </p><p>Email: <a rel="noopener noreferrer nofollow" href="mailto:2guystalkingit@gmail.com" target="_blank">2guystalkingit@gmail.com</a></p><p></p><hr /><p></p><h2>Chapters</h2><p>00:19 Intro </p><p>03:32 Welcome Nick </p><p>04:22 What functional dyspepsia is, and why it's probably several diseases </p><p>06:48 Rome V, and why "functional" is a terrible word </p><p>08:14 How Nick explains the diagnosis to patients </p><p>09:00 Workup and first-line treatment: scoping, routine duodenal biopsies, PPIs, tricyclics, antihistamines </p><p>13:21 Adding an antihistamine on top of a PPI </p><p>13:49 Duodenal eosinophilia: can your pathologist actually see it? </p><p>15:43 EoE and functional dyspepsia: separate pathways </p><p>17:03 Six-food elimination, biologics, and the budesonide trial </p><p>19:28 The duodenal microbiome and swallowed streptococci </p><p>22:20 Refractory disease: mirtazapine, SNRIs, quetiapine, hypnotherapy 26:01 Smoking, alcohol, NSAIDs, exercise and diet </p><p>29:08 Exclusive enteral nutrition </p><p>30:02 Gastric emptying, gastroparesis, G-POEM and rumination </p><p>33:50 Cyclic vomiting syndrome </p><p>36:39 Why amitriptyline and not nortriptyline </p><p>37:51 Breath testing: what's useful and what's worthless </p><p>40:39 What Nick is excited about in the next five years </p><p>44:11 A weird and wonderful therapy for IBS </p><p>46:27 A career in academic medicine </p><p>50:42 Why pharma abandoned DGBI </p><p>52:16 Wrap-up</p>
June 12, 2026
<p>We're back for Season 2, and Jon and James kick things off with one of their favourite topics: Incretin mimetics. The gut is the biggest endocrine organ in the body, and the data in steatotic liver disease is now as good as anything we have in Hepatology for steatotic liver disease.</p><p></p><p>James and Jon cover the basic pharmacology, how to start and titrate these drugs in practice, what to tell patients about stopping them, the muscle loss question, endoscopy and anaesthesia, and a brief look at where the evidence is going across cardiovascular disease, kidney disease, sleep apnoea, IBD, and cancer. There is a lot going on with these drugs and this episode is the primer.</p><p></p><p>As always comments, questions, feedback and suggestions please send to: </p><p>X: @2guystalkingit </p><p>Email: <a rel="noopener noreferrer nofollow" href="mailto:2guystalkingit@gmail.com" target="_blank">2guystalkingit@gmail.com</a></p><hr /><h2>Chapters</h2><p>00:00 Intro: Season 2 is here </p><p>03:00 What are incretins? The gut as endocrine organ </p><p>06:30 Origin story: Gila Monster and the GLP-1 breakthrough 08:30 The drugs: semaglutide, tirzepatide, and what's coming 10:00 How they actually work: satiety, the brain, and fat oxidation </p><p>12:00 Who to start: patient selection and caution groups </p><p>13:30 Lean MASH and Southeast Asian BMI thresholds </p><p>16:00 Exercise, muscle loss, and the resistance training argument </p><p>18:30 Side effects: nausea, constipation, lipase, mood </p><p>21:00 Endoscopy and anaesthesia: what to do </p><p>24:00 Titrating in practice: James's approach </p><p>28:00 Stopping the drug: weight regain and the SURMOUNT data </p><p>33:00 Personalising treatment: who can stop, who shouldn't 35:00 Eating disorders, body image, and screening </p><p>37:00 MASH data: ESSENCE and Synergy-NASH trials </p><p>39:30 Oral formulations: what's available and caveats </p><p>40:30 Where bariatric surgery still fits </p><p>42:00 Broader indications: IBD, CVD, CKD, cancer </p><p>45:00 Global obesity trends and the public health message 47:00 Wrap-up</p><hr /><h2>Papers discussed</h2><p><a rel="noopener noreferrer nofollow" href="https://www.nejm.org/doi/full/10.1056/NEJMoa2413258" target="_blank">ESSENCE trial</a></p><p><a rel="noopener noreferrer nofollow" href="https://www.nejm.org/doi/abs/10.1056/NEJMoa2401943" target="_blank">Synergy-NASH trial</a></p><p><a rel="noopener noreferrer nofollow" href="https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(26)00656-2/abstract" target="_blank">SURMOUNT-MAINTAIN</a></p><p><a rel="noopener noreferrer nofollow" href="https://www.cell.com/cell-metabolism/abstract/S1550-4131(25)00114-7" target="_blank">Tirzepatide and fat oxidation, Cell Metabolism 2025</a></p><p><a rel="noopener noreferrer nofollow" href="https://pmc.ncbi.nlm.nih.gov/articles/PMC11227080/" target="_blank">GLP-1 receptor agonists and 13 obesity-associated cancers</a></p><p><a rel="noopener noreferrer nofollow" href="https://www.nejm.org/doi/full/10.1056/NEJMoa2307563" target="_blank">SELECT trial</a></p><p><a rel="noopener noreferrer nofollow" href="https://www.nejm.org/doi/10.1056/NEJMoa2403347" target="_blank">FLOW trial</a></p><p><a rel="noopener noreferrer nofollow" href="https://www.nejm.org/doi/10.1056/NEJMoa2404881" target="_blank">SURMOUNT-OSA</a></p><p><a rel="noopener noreferrer nofollow" href="https://www.nejm.org/doi/10.1056/NEJMoa2403664" target="_blank">STEP 9: Semaglutide in obesity and knee osteoarthritis</a></p><p><a rel="noopener noreferrer nofollow" href="https://acrjournals.onlinelibrary.wiley.com/doi/10.1002/art.70134" target="_blank">Psoriatic Arthritis paper</a></p>
June 8, 2026
<p>We're back. After a longer-than-planned hiatus involving life, work, and the general chaos of being two busy clinicians: Two Guys Talking $#it is returning for Season 2.</p><p></p><p>The spark? Jon got stopped in a hospital corridor by a non-gastro colleague who'd been listening to the IBS episode with Alex Ford and had shared it with her neighbour. Turns out the show has fans in unexpected places, and that was enough to get us back in front of a microphone.</p><p></p><p>Season 2 kicks off with one episode a month and a lineup that already has a few things in the works. Same format, same vibe, no Backstreet Boys cover. Glad to have you back.</p><p></p><p>As always comments, questions, feedback and suggestions please send to:<br />X: @2guystalkingit<br />Email: <a rel="noopener noreferrer nofollow" href="mailto:2guystalkingit@gmail.com" target="_blank">2guystalkingit@gmail.com</a></p>
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“Two Guys Talking $#it” is a podcast where two Gastroenterologists break down complex topics into engaging, educational, and occasionally humorous conversations. From liver health to gut microbiota and everything in between, A/Professor Jonathan Segal and Dr James Haridy deliver insights, share the latest research, and discuss clinical pearls with the odd guest in tow.
Comments, suggestions, questions please contact us on twitter @2guystalkingit or leave a comment below..
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