How do I convert the TRIUMPH-3 hazard ratio into an absolute risk reduction?

My laboratory results are from the same laboratory each time, drawn fasting, which I gather matters.

I want the working, not the result — I need to be able to redo it with different numbers.

I care about the precision as well as the value — I want to know how many figures are real.

Is my approach right even if my number is wrong?

Answer first: the cardiovascular signal in this class is a reduction in major adverse cardiovascular events in populations already at elevated risk, not a general cardioprotective claim for everyone.

A twenty per cent relative reduction on a baseline three-year event rate of eight per cent is an absolute reduction of about one and a half points, which is a number-needed-to-treat somewhere in the region of sixty to seventy. Both framings are true and they read very differently.

The heart-failure question is separate again, and the evidence there is largely in the preserved-ejection-fraction population with obesity, where the trials measured symptoms and function rather than mortality.

SELECT is the trial to read for primary-prevention-adjacent populations without diabetes; SUSTAIN-6 and LEADER are the diabetes-population outcome trials for semaglutide and liraglutide respectively.

Ask for the absolute risk reduction and the number needed to treat. If a source will not give you both, it is selling something.

What the outcome trials established is that the class does not increase cardiovascular risk and, in the higher-risk populations studied, reduces it. Those are two separate findings from the same programme.

Baseline risk decides how much the relative reduction is worth. The same twenty per cent applied to a one per cent annual risk and a five per cent annual risk produce very different absolute numbers.

Mechanically, cardiovascular composites in this programme are typically cardiovascular death, non-fatal myocardial infarction and non-fatal stroke. When one component drives the result, that is worth knowing, because the components differ in how much they matter.

The cardiovascular safety requirement for new glycaemic agents is why these trials exist at all: regulators required an outcome programme, and the benefit finding was in that sense an unexpected dividend.

These are trial populations on licensed product. Research-grade material of unverified content is not the thing that was studied.

Read SELECT for the without-diabetes population and the earlier outcome trials for the with-diabetes one. They are not the same result.

The short version: real effect, modest absolute size, largest in those with the highest baseline risk — which is the ordinary shape of a cardiovascular result.

Resting heart rate rises by roughly two to four beats per minute across the class. The mechanism is not fully settled, the magnitude is consistent, and it has not translated into an adverse outcome signal in the trials that looked.

Heart-rate elevation in this class is documented consistently enough across agents that it should be treated as a class effect rather than as a finding about any one molecule.

Heart rate up a few beats, blood pressure down a few millimetres, events down about a fifth in high-risk populations. That is the honest summary.

edited 10 Jul 2025 by Dr_Bram_Verhoeven — removed a claim I could not source

More usefully, the mechanism question and the outcome question are separate. The outcome data stand whether or not the mechanistic story is settled, and the mechanistic story is not settled.

SELECT randomised people with established cardiovascular disease and overweight or obesity but without diabetes to semaglutide 2.4 mg, and reported roughly a twenty per cent relative reduction in the primary composite. The absolute difference over about three years was on the order of one and a half percentage points.

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].

Nothing here is medical advice. If cardiovascular risk is the actual question, it is a conversation for a clinician with your numbers in front of them.

Population, baseline risk, endpoint definition. In that order, then the effect size.