The Curbsiders Internal Medicine Podcast #517 DIGEST: Weight regain after weight loss medications, GLP1/GIP comparisons, valacyclovir for Alzheimer’s, and nudges to encourage deprescribing
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Mar 16, 2026 A rapid review of GLP-1 and GIP therapies, emerging triple-agonists, and cardiovascular trial signals. A look at patterns of weight regain after stopping medication and counseling implications. A surprising trial where valacyclovir worsened cognition in early Alzheimer’s. Behavioral nudges to increase deprescribing and the practical tradeoffs of alerts and clinician burden.
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New Incretin Combinations Are Driving Bigger Weight Loss
- The GLP-1/GIP pipeline is expanding with oral small-molecule GLP-1s, triple agonists like retatrutide, and amylin combos offering larger weight loss than current agents.
- Nora and Matt note retatrutide (GLP‑1/GIP/glucagon) showed ~30–35% weight loss in trials and cagrilentide+semaglutide is in phase 3 for added satiety benefit.
Tirzepatide Shows Cardiovascular Safety Signal In SURPASS‑CVOT
- SURPASS‑CVOT found tirzepatide non-inferior to dulaglutide for major adverse cardiovascular events in people with T2DM and CVD, supporting a cardiovascular indication.
- Alex and Matt emphasize benefits correlate with weight loss and practical prescribing hinges on insurance coverage and indications.
Weight Rapidly Returns After Stopping Antiobesity Drugs
- Stopping weight‑loss meds leads to predictable regain; pooled data show ~0.4 kg/month after cessation and ~0.8 kg/month for incretin mimetics.
- Meta-analysis projects return to baseline weight in ~1.7 years with parallel rises in A1C, BP, and cholesterol.
