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An approach dive on what GLP-1 receptor agonists actually do beyond glucose and weight, built to answer the question Monday's sweep left open — that the evidence for anything harder than weight loss is thin. It starts with a new FPIN help desk answer in the August American Family Physician on GLP-1s and stroke prevention, and uses its second cited study as a worked example of immortal time bias and the healthy-user effect, since the study reports that urinary tract infections and candidiasis were less common in drug users, which no drug does. It then walks the outcome trials one at a time with PICO — SELECT for cardiovascular prevention without diabetes, FLOW for kidney disease, SOUL for oral semaglutide, STEP-HFpEF for heart failure with preserved ejection fraction, and STRIDE for peripheral artery disease — decomposing the composite endpoints to show which component is carrying each result. It closes on SURPASS-CVOT and the August 2026 FDA approval of tirzepatide for cardiovascular risk reduction, which is the first of these granted on noninferiority to an active comparator rather than superiority to placebo, and on the NAION labeling change European regulators made in June 2025.

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A pediatrics episode on headache in children and adolescents, built on the Cribsiders episode with pediatric neurologist John Gaitanis and updated with two things that changed after it aired. The first is the August 2025 FDA approval of fremanezumab for episodic migraine down to age six, which makes a CGRP monoclonal antibody a pediatric option for the first time; the second is the March 2025 labeling change across the whole CGRP class for hypertension and Raynaud phenomenon. The episode covers how to take a headache history from a child who cannot give you one, the red flags that actually earn imaging and the far longer list that does not, why pediatric migraine looks different from adult migraine in the diagnostic criteria themselves, the CHAMP trial and its enormous placebo response, the acute and preventive drug options with doses, and the documented diagnostic disparity by race. It closes on the combined oral contraceptive and migraine-with-aura question, where the American and European guidance disagree.

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I cannot remove this autotext; do not send me a voice note. Largely drawn from Penn Primary Care's recent two-part series