What I have: a GLP-1 receptor agonist · cagrilintide.
I have used one of these for a while and I am considering switching, which requires a reason.
What I care about is reproducibility, because a result I cannot repeat is not useful to me.
Which axes does this decision turn on?
Put another way, read the estimand before the effect size. Almost every apparent contradiction between two published figures from the same trial resolves once you notice that one is a trial-product estimand and the other is a treatment-policy estimand.
Creatinine is a muscle-derived metabolite, so a substantial loss of lean mass lowers serum creatinine and mathematically raises estimated GFR without anything happening to the kidney. If you have lost twenty kilograms, your creatinine-based eGFR is flattering you. Cystatin C is not muscle-dependent and is the measure to use when the two disagree.
HbA1c is a weighted average, not a flat one: roughly half the signal comes from the most recent month. That is why a value drawn six weeks after a change already reflects most of the effect, and why a value drawn during rapid haematological turnover reflects something other than glycaemia.
SELECT reported a hazard ratio of 0.80 (95% CI 0.72–0.90) for the primary composite major adverse cardiovascular event endpoint with semaglutide 2.4 mg in overweight or obese adults with established cardiovascular disease and without diabetes[1].
Read the confidence interval, read the estimand, and compute the absolute effect yourself. It takes two minutes and it changes how the result feels.
edited 13 Aug 2024 by Dr_Colm_Fitzhenry — expanded the table to cover the lower concentration
Aggregated, published test results and vendor ratings built from submitted batches. Methodology stated, dataset browsable, no listing fees.
Browse resultsStart with the population. The inclusion criteria of the trial determine what its result can be extrapolated to, and the extrapolation people want is usually to a population the trial excluded.
Absolute risk reduction, worked: if the control-arm event rate is 8.0 per cent over the follow-up period and the hazard ratio is 0.80, the treated rate is approximately 6.4 per cent, the absolute risk reduction is 1.6 percentage points, and the number needed to treat is 1 ÷ 0.016 ≈ 63 over that period. A 20 per cent relative reduction and a number needed to treat of 63 are the same finding stated two ways, and only one of them sounds impressive.
Worth being precise here: apoB and LDL-C disagree because they measure different things: LDL-C is the cholesterol mass carried in the LDL fraction, ApoB is a count of atherogenic particles. Small dense particles carry less cholesterol each, so a person with many small particles has a concordantly higher ApoB than their LDL-C suggests. When they disagree, ApoB is the better risk marker.
The caveat is the population. Trial participants were screened, monitored and supported; the effect size in an unmonitored setting is not the trial effect size, and it is not obvious in which direction the difference runs.
If the trend across three draws is flat, the difference between draws one and two was noise. Most of what people react to is noise.
It helps to be literal here: a single laboratory value is a point on a noisy curve. What you want is a trend across at least three draws under comparable conditions, and "comparable" is doing a lot of work in that sentence.
Estimated average glucose from HbA1c: eAG in mg/dL = 28.7 × A1c − 46.7, or in mmol/L, 1.59 × A1c − 2.59. An A1c of 6.5 per cent is therefore about 140 mg/dL or 7.8 mmol/L. The relationship is a population regression, so an individual can sit well off the line.
Liver enzymes are a poor surrogate for hepatic histology in both directions: substantial steatohepatitis with normal transaminases is common, and modest enzyme elevation with minimal fibrosis is common. If the question is fibrosis, the answer comes from a non-invasive score such as FIB-4 or a stiffness measurement, not from ALT.
STEP 1 reported a mean weight change of approximately −14.9 per cent with semaglutide 2.4 mg versus −2.4 per cent with placebo at 68 weeks[1]; the difference between the figures quoted from this trial in different places is an estimand difference.
The papers are readable. Read the paper rather than the summary of the paper, especially where the summary is enthusiastic.
This is a question about what the trial was designed to answer, and the honest response is that it was not designed to answer this.
The rodent thyroid C-cell findings that generated the labelled warning appear to be species-specific: rodent C-cells express GLP-1 receptors at high density, human C-cells at very low density, and human calcitonin data across large trial populations has not reproduced the signal. A family history of medullary thyroid carcinoma or MEN2 is nonetheless a genuine contraindication rather than a theoretical one.
Convert everything to an absolute effect before you compare two interventions. Relative effects are not comparable across different baseline risks.
The confidence interval is the informative part. A point estimate with an interval spanning no effect is a different object from the same point estimate with a tight interval, and the abstract presents them identically.
The early fall in estimated glomerular filtration rate on treatment is haemodynamic rather than structural. Reduced intraglomerular pressure lowers the filtration rate acutely and preserves the glomerulus chronically — the same pattern seen with renin-angiotensin blockade and with SGLT2 inhibition. A dip of a few millilitres per minute in the first weeks, followed by a shallower long-term slope, is the desired trajectory, not a warning sign.
SUSTAIN 6 was the original cardiovascular outcomes trial for semaglutide in type 2 diabetes and is the reference point for the class effect that SELECT later extended to a non-diabetic population[1].
I would resist reading a subgroup finding as a result. Subgroups in these trials were not powered, and a striking subgroup in a large trial is the expected consequence of multiplicity.
None of this replaces a clinician who can see the whole picture, and the whole picture is usually where the answer is.
edited 14 Jun 2024 by lipid_panel_q — tightened the wording; no substantive change
Ask PeptideStack is a static archive. Posting is closed, but the norms are worth stating: answer the question that was asked, show your working, cite the trial or the certificate, and say plainly where the evidence runs out.