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The obese brain goes leptin-deaf. One holdout neuron carries the GLP-1 drug target.

A mouse study in the EMBO Journal finds that when the obese brain stops responding to leptin almost everywhere, one neuron population keeps listening, and it is defined by the receptor the entire GLP-1 weight-loss class targets. It is the cleanest anatomical hint yet for why leptin failed as a drug and GLP-1 did not.

7d ago · GLP-1 · @pavel GLP-1RFAT-METABOLISM 3 min read
Lilly's amylin-tirzepatide combo hit 23.3%. Dropout ran as high as 27%.

Adding the amylin agonist eloralintide to tirzepatide produced 23.3 percent weight loss over 48 weeks against 14.8 percent for tirzepatide alone, Lilly reported at EASD. The extra 8.5 points came with adverse-event discontinuation of up to 27.0 percent across the combination arms versus 2.9 percent on tirzepatide by itself. Phase 3 will test a reformulated, co-formulated version with an adjusted dose-escalation, not the two-injection regimen from this Phase 2b.

10d ago · GLP-1 · @pavel CALCRGIPRGLP-1R 4 min read
Tirzepatide cost less per patient who hit target. Lilly authored the study.

A Lilly-authored US claims analysis found tirzepatide starters were more adherent and more likely to reach strict blood-sugar and weight goals than semaglutide starters, at a lower cost per responder. The eye-popping three-to-one gaps sit at the strictest targets, where the tiny denominator, not the molecule, does most of the work.

11d ago · GLP-1 · @pavel GIPRGLP-1R 4 min read
Adding Semaglutide to Dapagliflozin Tracked With Less Heart Failure But Worse Blood Sugar

A six-month study of 539 people with type 2 diabetes found that pairing dapagliflozin with once-weekly semaglutide tracked with a lower heart failure rate but worse blood sugar control. The retrospective, single-center design means the trade-off is an association, not proof the combination caused either result.

12d ago · GLP-1 · @pavel GLP-1R 3 min read
Enicepatide dropped HbA1c 2.65 points in phase 2, but Roche left the placebo column blank

Roche's September 22 topline for enicepatide (the former CT-388) is impressive on its face: a 2.65-point HbA1c fall and 15.5 percent weight loss over 48 weeks in 447 adults with type 2 diabetes. Every headline number is measured from each patient's own baseline. The one figure the release withholds is what the placebo arm did over the same year, which is the only comparison that tells you what the drug actually added.

14d ago · GLP-1 · @pavel GLP-1RGIPR 4 min read
GLP-1 obesity users split into five adherence paths. Only one in three adults stayed the course.

A MarketScan claims analysis of 201,229 adults and 1,139 children on GLP-1 drugs for obesity found five distinct patterns of use, from immediate dropout to persistent treatment. Only 30.7% of adults and 20.3% of children stayed on, and the Northeast held on more than the South.

22d ago · GLP-1 · @pavel GLP-1RGIPR 3 min read
GLP-1 drugs trimmed antipsychotic weight gain. The evidence base is 664 patients.

A pooled analysis of eight trials found GLP-1 drugs added to antipsychotics cut weight by about 15 pounds and moved blood sugar, with semaglutide the standout. The metabolic surrogates fell, the gut paid for it, and the early-death gap the drugs are meant to close went unmeasured.

24d ago · GLP-1 · @pavel GLP-1R 4 min read
GLP-1 drugs curb binge eating. A panel says screen before prescribing them.

A 45-expert Delphi panel in World Psychiatry set the first structured rules for GLP-1 weight-loss drugs and eating disorders: screen everyone first, generally avoid the drugs in active anorexia or bulimia, and offer psychotherapy alongside. The catch is that the guidance is formalized expert opinion, not evidence, because the studies to test it do not exist yet.

25d ago · GLP-1 · @pavel GLP-1R 4 min read
GLP-1 drugs did not change neck-fusion outcomes, but the study was too small to clear them

Surgeons worry the GLP-1 drugs slow healing after operations that depend on bone knitting. A meta-analysis of six retrospective cohorts and 17,310 patients found no signal across four cervical-fusion outcomes. The confidence intervals were wide enough to hide a real effect, so the null reads as underpowered, not safe.

25d ago · GLP-1 · @pavel GLP-1R 4 min read
GLP-1 users had fewer asthma flares. All four outcomes leaned one way.

In a matched US health-records study of obese asthma patients, GLP-1 users had about 56 percent fewer flares and fewer severe respiratory events over a year. Every outcome leaned the same way, which is also the signature of who gets the drug.

26d ago · GLP-1 · @pavel GLP-1RIMMUNE 4 min read
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