The shortage years, and what they taught about interruption
Cost is the modal reason for discontinuation in every dataset we have seen, and it is absent from the clinical literature.
Tirzepatide
Page 12 of 18 of this archive, newest first.
Eating enough protein on a suppressed appetite is an arithmetic problem before it is a nutritional one
The resistance-training and energy-deficit literature supports a higher protein intake. None of it was conducted in people taking an incretin.
A guide to the results that will resolve themselves
The panel drawn during a week of vomiting is measuring the vomiting.
Maintenance dosing: what is licensed, what is practised, and what is evidenced
Dose reduction is not withdrawal, and the trials that tested withdrawal cannot be read as testing it.
Why no trial in this class has reported a strength endpoint
The composition data comes from imaging substudies enrolling a few score participants at selected sites. It is the best evidence available and it is thin.
Non-responders, and the honest state of the evidence about them
The mechanism is well described. The variance is not.
Is semaglutide better than dulaglutide, or differently balanced?
What adding GIP activity does, on the current evidence, and what remains unresolved.
What the older diet-and-exercise trials found in the hip
Weight loss reduces bone mineral density at load-bearing sites. Whether that translates into fractures in this population is unmeasured.
Sarcopenia is a diagnosis, not a synonym for losing lean mass
The gap between a defensible recommendation and a confident one is where most of the harm in this subject lives.
Why receptor selectivity is the least discussed number in incretin pharmacology
The class is described as though every molecule in it did the same thing. At the receptor, they demonstrably do not.
What we would need to measure to explain the response distribution
A catalogue of open questions, with an assessment of how likely each is to be resolved.
What we would need to randomise to answer this properly
One randomised trial has combined a GLP-1 receptor agonist with supervised exercise. Its result is the single most useful piece of evidence in this area.
Non-responders, and the honest state of the evidence about them
A catalogue of open questions, with an assessment of how likely each is to be resolved.
Two sessions a week, and the evidence behind the prescription
The recommendation survives scrutiny. The reasoning offered for it frequently does not.
Bone density during rapid weight loss: what is known, which is less than you would hope
The evidence base is one secondary analysis, several small studies and a large amount of extrapolation from bariatric surgery.
A supply gap is a pharmacological event
One omitted dose is a labelling question. Four omitted doses is a clinical one. The two are routinely conflated.
Randomised withdrawal is the cleanest design in this field and the least discussed
The regain trajectories, arm by arm, with the estimands named.
Why "muscle-sparing" is a marketing term and not a measurement
The rule that a quarter of weight lost is lean tissue has been in textbooks for decades and does not survive close reading.
Is survodutide better than retatrutide, or differently balanced?
Head-to-head data exists for some of these comparisons and not for others. This piece says which.
The out-of-range flag is a statistical convention with a printer attached
A flag is a probability statement about a population. It is not a statement about the person holding the printout.