Podcast Summary

Podcast: The Curbsiders Internal Medicine Podcast
Episode: #514 Hotcakes: Oral Semaglutide, Fish Oil in ESRD, IV Iron During Infection, New US Dietary Guidelines, & Anticoagulation after Ablation in AFib
Date: February 16, 2026
Hosts: Dr. Matthew Watto, Dr. Paul Nelson Williams, Dr. Rahul Ganatra, Dr. Joshua Gilman

Episode Overview

In this "Hotcakes" episode, the Curbsiders team critically appraises a selection of recent, practice-changing articles covering oral semaglutide for obesity, fish oil for cardiovascular risk in dialysis, the safety of IV iron during acute infection, the new US Dietary Guidelines, and anticoagulation management after AFib ablation. The conversation blends clinical insights, methodological scrutiny, humor, and multiple mini-rants on study title acronyms and dietary infographics.

1. Oral Semaglutide for Weight Loss

Segment: 03:12–12:15
Presenter: Dr. Matthew Watto

Key Points

• Background: Oral semaglutide, previously available for diabetes, is now approved for obesity at a higher dose (25 mg).
• Wharton et al. (NEJM 2025): Phase 3 randomized controlled trial; adults with overweight/obesity received oral semaglutide.
  • Results:
    • 13.6% weight loss (semaglutide) vs. 2.2% (placebo); difference -11.4 percentage points.
    • High rate of GI side effects: nausea (~50%), vomiting (~33%).
    • About 20% of participants did not complete the trial, primarily due to adverse effects.
  • Dosage: Stepwise escalation over 12 weeks; maintenance at 25 mg.
  • Cost: Potentially ~$300/month, cheaper than injectable (no pen device).

Notable Quotes

• “Any medication that I prescribed a patient where those patients would then throw up as a result is something that gives me pause regardless of the efficacy.” – Dr. Paul Williams [09:36]
• “I think the drug companies are gonna keep tweaking the formulation... Maybe it’s a dual or tri peptide that's going to give less side effects.” – Dr. Matt Watto [09:51]

Clinical Pearls

• GI side effects are common and dose-dependent.
• Dysesthesia, a previously under-recognized side effect, reported in ~5% of patients at higher doses.

Hotcakes Rating: 3.5/5 (Watto) – “Not that exciting, but important to know it’s out there.” [12:15]

2. Fish Oil for Cardiovascular Events in Hemodialysis Patients (PISCES Trial)

Segment: 15:23–26:53
Presenter: Dr. Paul Williams

Key Points

• Locke et al. (NEJM 2026): Multicenter, double-blind, placebo-controlled RCT in Canada and Australia.
  • Question: Does high-dose fish oil reduce CV events in hemodialysis patients?
  • Intervention: 4g/day of purified fish oil (1.6g EPA, 0.8g DHA); placebo = citrus-flavored corn oil.
  • Results:
    • ~40% lower rate of cardiovascular events in fish oil group (HR 0.57).
    • No increased rate of serious bleeding.
    • Study cohort was a relatively healthier dialysis population (excluded HF, recent hospitalization, etc.).
• Dosing Caveat: OTC fish oil supplements are typically lower quality/dose than used in the trial.

Notable Quotes

• “This is the reason I looked into this in the first place… the PISCES trial, buddy… they nailed the acronym, knocked it out of the park!” – Dr. Paul Williams [26:01]
• “I’m ready to start giving this to patients if it’s kind of harmless and leads to cardiovascular reduction.” – Dr. Rahul Ganatra [23:26]

Debate

• Unclear mechanism behind the observed benefit; apprehension that improvement may be modest.
• Awareness of confounding from public enthusiasm for fish oil and variability in supplement quality.

Hotcakes Rating: 5/5 (Williams) – “Thrilled by this study! Practice-changing.” [26:53]

3. IV Iron During Acute Infection

Segment: 27:31–39:08
Presenter: Dr. Rahul Ganatra

Key Points

• Sohail et al. (Blood, 2026): Retrospective, real-world study (TriNetX database).
  • Question: Is IV iron safe (even beneficial) in hospitalized patients with iron-deficiency anemia and acute infection?
  • Findings: IV iron administration was associated with improved 14- and 90-day survival (up to ~50% RR reduction).
• Methodological Concerns:
  • Immortal Time Bias: Patients had to survive long enough to receive iron – inherently healthier.
  • Propensity Score Matching was used, but residual confounding and missing data limit confidence.
  • Effect Size: Large reduction in mortality with minor change in Hb raises plausibility concerns.

Notable Quotes

• “These results are at high risk of being fully explained by immortal time bias. …This definitely biases towards increased survival in that group and really limits our ability to draw inferences…” – Dr. Rahul Ganatra [34:00]
• “I want it to be true that IV iron is safe in the setting of infection. …But I’m very mistrustful of the 50% relative reduction in mortality.” – Dr. Rahul Ganatra [36:14]

Hotcakes Rating: 1/5 (Ganatra) – “Want this to be true, but only one steam deodorized citrus-scented hotcake.” [38:44]

4. New US Dietary Guidelines

Segment: 42:14–51:30
Presenter: Dr. Rahul Ganatra

Key Points

• Major update released by US government (2026), shaping nutrition policy (SNAP, National School Lunch, etc.).
• Good Elements: Strong recommendations to reduce added sugars, refined carbs, processed foods; prioritize whole foods, fruits, veggies, whole grains.
• Controversial Changes:
  • Protein: Recommends 1.2–1.6g/kg/day (vs. old guideline 0.8g/kg), not fully supported by scientific supplement.
  • Fat: Document lists butter/beef tallow as alternatives to olive oil, despite known LDL/CV risks.
  • Graphic Concern: Steak and cheese visually prominent; could mislead public about portion priorities.
• Impact: Guidelines influence federal nutrition programs more than individual choices.

Notable Quotes

• “It feels like this is in keeping with a larger practice of putting something that sounds reasonable as a vehicle to carry some junk science and garbage that is not reasonable and not actually backed by evidence.” – Dr. Paul Williams [45:25]
• “The protein targets… I have less of a problem with. People should be doing resistance training… Most people are probably getting 1.2g/kg anyway.” – Dr. Matt Watto [50:03]

Overall Take

• “Eat whole foods, eat some vegetables; don’t double down on saturated fats.”
• Cultural meme-ification of recommendations may dilute focus on evidence-based updates.

5. Anticoagulation After AFib Ablation (ALONE-AF & OCEAN Trials)

Segment: 51:30–67:41
Presenter: Dr. Josh Gilman

Key Points

• ALONE-AF (JAMA Aug 2025): South Korean multicenter RCT.
  • Question: Can anticoagulation be safely stopped after successful catheter ablation for AFib?
  • Design: Post-ablation patients without recurrence (confirmed by multiple Holter monitors) randomized to continued vs. discontinued anticoagulation. Follow-up: 2 years.
  • Results: Discontinuation group had fewer composite adverse events (1 stroke/systemic embolism/major bleed vs. 8 in continuation; ARR ~1.9%).
  • Key Driver: Benefit due to less bleeding, not increase in stroke.
  • Population: Mean CHA₂DS₂-VASc ≈ 2 (lower-risk).
• OCEAN Trial (NEJM 2026):
  • Similar design, larger sample; open-label, compared rivaroxaban vs. aspirin after AF ablation.
  • Results: Very low event rates in both arms; no difference in major outcomes, but slightly more major bleeds on anticoagulation.
  • Unique feature: All had post-trial MRI for covert stroke.
• Clinical Implications:
  • Existing CHA₂DS₂-VASc scoring may not accurately predict risk in post-ablation patients in stable sinus rhythm.
  • Data support safely stopping anticoagulation in lower-risk, well-monitored, post-ablation patients without recurrent AF.

Notable Quotes

• “I see such a large number of patients who are thinking, how do I get off anticoagulation? …To see this opportunity is really exciting.” – Dr. Josh Gilman [61:14]
• “Medicine remains endlessly exciting… the fact that this is a conversation we’re having now… it just… wow.” – Dr. Paul Williams [60:49]
• “Maybe we need to devise a new scoring system for patients that remain in normal sinus rhythm after catheter ablation.” – Dr. Josh Gilman [67:30]

Trial Name Humor

• “AF alone af dude, this trial name is psychotic… Anticoagulation one year after ablation for atrial fibrillation in patients with atrial fibrillation alone… atrial fibrillation is in the title seven times… Incredible to me!” – Dr. Paul Williams [61:56]

Hotcakes Rating: 4.5–4.75/5 (Gilman) – “Well-designed, generalizable, and likely to change practice.” [62:58]

Timestamps for Major Segments

• Oral Semaglutide: 03:12–12:15
• Fish Oil in Hemodialysis (PISCES): 15:23–26:53
• IV Iron During Infection: 27:31–39:08
• US Dietary Guidelines: 42:14–51:30
• Anticoagulation after AFib Ablation (ALONE-AF, OCEAN): 51:30–67:41

Bottom Line Clinical Takeaways

• Oral Semaglutide: Highly effective for weight loss, but GI side effects limit adherence; cheaper oral formulation now available.
• Fish Oil in ESRD: High-dose, well-formulated fish oil may significantly reduce CV events in select hemodialysis patients—practice-changing for nephrology.
• IV Iron in Infection: Retrospective data suggesting benefit likely explained by immortal time bias; safety still unproven—do not change practice yet.
• Dietary Guidelines: Emphasize whole foods, less processed sugar; be skeptical of high-protein/fat guidance not evidence-based; watch federal policy roll-out.
• Post-Ablation Anticoagulation: Can (carefully) consider stopping anticoagulation in stable, low-risk post-ablation patients with good rhythm monitoring—likely to impact guidelines and patient management.

Notable Quotes & Memorable Moments

• “This is the reason I looked into this in the first place… the PISCES trial, buddy… they nailed the acronym, knocked it out of the park!” – Paul [26:01]
• “Any medication that I prescribed a patient where those patients would then throw up as a result is something that gives me pause regardless of the efficacy.” – Paul [09:36]
• “These results are at high risk of being fully explained by immortal time bias. …This definitely biases towards increased survival in that group and really limits our ability to draw inferences…” – Rahul [34:00]
• “This is my dream… happy to vet your journal article titles if it pays about the same.” – Paul on being a trial name consultant [62:40]
• “Maybe we need to devise a new scoring system for patients that remain in normal sinus rhythm after catheter ablation.” – Josh [67:30]

Podcast Mood and Tone

Conversational, witty, collegial, with honest critical appraisal of studies—balancing humor (especially about acronyms and dietary graphics) with evidence-based clinical skepticism. The hosts encourage independent judgment and always “do your own homework,” fostering critical literacy among internal medicine peers.