The glucagon receptor arm, and why it is the hardest to reason about
A dual agonist is one molecule with two receptor activities. A co-formulation is two molecules in one pen. The coverage treats them as synonyms.
Semaglutide
Page 6 of 18 of this archive, newest first.
A year after stopping: what the trials found at the far end
The variance around the mean regain trajectory is large and unexplained, exactly as it is for the weight loss.
The dose that got you here and the dose that keeps you here
A survey of the maintenance evidence, which is shorter than the survey of the withdrawal evidence.
Diminishing returns, quantified
Where the curve flattens, what flattens with it, and what does not.
Non-responders, and the honest state of the evidence about them
The mechanism is well described. The variance is not.
What SELECT tells us about maintenance, and what it does not
Dose reduction is not withdrawal, and the trials that tested withdrawal cannot be read as testing it.
The ceiling is a tolerability finding, not an efficacy one
Higher doses of these molecules have been studied. In general they produced modest additional efficacy and disproportionate additional symptom burden, which is why the…
Load, not cardio: the distinction the general advice keeps losing
Mass and function are different endpoints and training affects them differently. Most coverage treats them as one.
Dual, triple, co-formulated: a taxonomy the coverage keeps collapsing
Head-to-head data exists for some of these comparisons and not for others. This piece says which.
Diminishing returns, quantified
Escalation beyond the label is common in this market. Reporting that it happens is not the same as reporting that it works.
Why the fifth week of a mazdutide dose feels different from the first
The exposure curve explains the timing of both the benefit and the side effects. It is almost never shown to the person injecting.
The supplement trade found this drug class quickly, and the citations did not improve
A survey of what the meta-analyses support, with the populations named.
The label says four weeks. The clinic says whatever holds.
The published ladder exists because a protocol needed a single number. Practice has never followed it exactly, and the regulatory file never assumed it would.
SURPASS-3 was built to answer the stopping question, and it did
Three randomised withdrawal designs have tested what happens when treatment stops. Their results are consistent and they are consistently misreported.
The shortage years, and what they taught about interruption
Why the reason for stopping changes what happens afterwards.
What the trial protocols permitted, and what the labels omitted
Reducing a dose is not going backwards. In a tolerability-limited class it is the mechanism by which the ceiling is found.
Do you need the top of the ladder?
What the trials measured was continuation against withdrawal. What patients want to know is continuation at a lower dose, and that study has largely not been done.
What TRIUMPH-1 tells us about maintenance, and what it does not
Dose reduction is not withdrawal, and the trials that tested withdrawal cannot be read as testing it.
What STEP 4 and SURMOUNT-4 actually established
Weight reduction in the long programmes flattens at roughly sixty to seventy-two weeks. The timing is consistent, predictable and almost never mentioned in advance.
What the outcome trials measured in the kidney
Estimated glomerular filtration rate is a calculation with muscle mass in the denominator of its assumptions. In this population that matters.