Is ALT worth drawing at baseline before starting cagrilintide?

What I am working with: ALT · cagrilintide.

I would like to set this up properly once, rather than adjust it repeatedly.

My budget is real but not tight, and my tolerance for uncertainty is low.

What would you do, and what would make you change course?

Start 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.

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.

Headline results, principal programmes

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.

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.

One qualification: a trial that demonstrates an endpoint at a given dose has demonstrated it at that dose. Extrapolating the endpoint down the dose ladder is an assumption, not a finding.

None of this replaces a clinician who can see the whole picture, and the whole picture is usually where the answer is.

edited 23 Dec 2025 by ravenna_pace — updated for the 2026 guidance change

Concretely, 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 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.

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.

SURMOUNT-1 reported mean weight reductions of approximately 15, 19 and 21 per cent at tirzepatide 5, 10 and 15 mg respectively at 72 weeks[1].

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.

Convert everything to an absolute effect before you compare two interventions. Relative effects are not comparable across different baseline risks.

In practice, the hazard ratio is the relative effect. What changes decisions is the absolute effect, and converting between them requires the event rate in the control arm, which is usually in the same table and rarely in the abstract.

A fasting lipid panel drawn during rapid weight loss reads oddly for a mechanical reason: mobilised adipose tissue delivers free fatty acids to the liver, and hepatic triglyceride export rises. Triglycerides can transiently increase while the person is doing exactly the right thing. Draw the panel when weight has been stable for a few weeks if you want an interpretable number.

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.

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.

The papers are readable. Read the paper rather than the summary of the paper, especially where the summary is enthusiastic.

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.

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.

FLOW tested a composite renal endpoint — kidney failure, sustained 50 per cent eGFR decline, or renal or cardiovascular death — in type 2 diabetes with chronic kidney disease, and was stopped early for efficacy[1].

Worth being explicit that this is interpretation of published data and not medical advice. Laboratory results belong in a conversation with whoever ordered them.

Read the confidence interval, read the estimand, and compute the absolute effect yourself. It takes two minutes and it changes how the result feels.

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.

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 PIONEER programme established oral semaglutide’s efficacy and the constraints on its administration, and the bioavailability figure of roughly one per cent is what drives the fasting and water-volume requirements[1].

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.