Cagrilintide vs semaglutide: one trial gave each of them alone, and semaglutide won

This one has a direct answer, which is rare on this site. The trial that made the combination famous also randomised people to each drug alone. Over 68 weeks at the same dose, semaglutide produced 16.1% weight loss and cagrilintide 11.8%, against 2.3% on placebo.

Cagrilintide is the addition, not the base. Its own monotherapy evidence puts it at about 6% against placebo in pooled analysis, and the development programme uses it on top of semaglutide rather than instead of it.

Semaglutide also has something cagrilintide has nothing of. A cardiovascular outcome trial in 17,604 people, where it cut cardiovascular death, heart attack and stroke by a fifth over about three and a half years.

They work on different satiety systems, which is the reason to combine rather than choose: GLP-1 for one, the amylin receptors for the other.

Status. Semaglutide is approved and prescribed. Cagrilintide is investigational and available only in trials.

The two middle rows are the comparison. Same trial, same 68 weeks, same 2.4 mg dose, same population, randomised allocation. Almost every comparison on this site has to be hedged because the figures come from different studies; this one does not.

Semaglutide alone beat cagrilintide alone by about four and a half percentage points, which is roughly a third more weight loss. Both beat placebo comfortably.

One caveat belongs here. These arm-level figures are the manufacturer's, reported under the estimand that asks what the drug does when taken as intended. The published paper reports the combination arm as -20.4% under a different estimand, which is explained on the CagriSema page. The relationship between the two monotherapy arms is unaffected, because both are counted the same way.

Outside that trial, cagrilintide's own evidence is thinner than its partner's. A 2026 meta-analysis of four randomised trials in 5,425 participants found cagrilintide monotherapy produced significant reductions in body weight (MD: -6.08%; MD: -5.89 kg) and blood pressure, without meaningful HbA1c improvement.

Two things in that sentence matter. The weight figure, around 6%, is well below what the same analysis found for the combination and below the 11.8% in the trial arm, which is what happens when shorter and smaller trials are pooled with longer ones. And the absence of an effect on HbA1c marks the clearest difference between the two drugs: semaglutide lowers blood sugar and cagrilintide, on its own, does not meaningfully.

That is the honest summary of cagrilintide alone: a real weight effect, smaller than semaglutide's, without the glycaemic benefit, in a compound that is not approved anywhere.

The asymmetry in the bottom rows is what the weight percentages do not show. Semaglutide has been followed for years in a population at cardiovascular risk and reduced events; cagrilintide has not been followed for outcomes at all.

Semaglutide copies GLP-1, a hormone released from the gut after eating, which slows gastric emptying, signals fullness and improves insulin secretion.

Cagrilintide copies amylin, which the pancreas releases alongside insulin and which acts through calcitonin and amylin receptors in the brainstem. It also slows gastric emptying, by a different route, and is engineered to last a week.

A 2026 cross-species study showed how separate the two pathways are: silencing a specific brainstem neuron population abolished cagrilintide's effect in rats while leaving semaglutide's intact. Two drugs reaching different cells is the reason the combination adds up, and it is also why choosing between them is a different question from choosing between two GLP-1 drugs.

Both were given at 2.4 mg once weekly by subcutaneous injection in the trial that compared them, which is what makes that comparison clean. Semaglutide's 2.4 mg is its approved weight-management dose, reached after a 16-week escalation. Cagrilintide has no approved dose, because it has no approval.

Cagrilintide's full dose detail, including the lower 1.0 mg arms used in the diabetes trials, is on its own record.

Semaglutide is an approved medicine, prescribed for type 2 diabetes and for weight management, with a label and a supply chain.

Cagrilintide is investigational. It has never been approved anywhere as a single agent, and its route to market is as half of the fixed-dose combination, which is itself not yet approved. There is no legitimate way to obtain cagrilintide alone.

Records: cagrilintide, semaglutide, and the combination at CagriSema.

Supported: semaglutide alone produces more weight loss than cagrilintide alone, measured directly in one trial at matched doses; cagrilintide alone produces a real but smaller effect, around 6% in pooled analysis, without a meaningful effect on blood sugar; the two together beat either; semaglutide reduces cardiovascular events and cagrilintide has no outcome data.

Not supported: that cagrilintide is an alternative to semaglutide, since the programme treats it as an addition and there is no approved product; that its tolerability advantage is established, since the comparison of adverse events between the monotherapy arms is not published at that level; that any of this describes material sold outside the trials.

The practical answer to the question people ask is that it is not a choice anyone currently has: one of these is a medicine and the other exists only inside a development programme.

1. Treating cagrilintide as the more powerful new drug. Alone it produced less weight loss than semaglutide in the trial that tested both.
2. Quoting the combination's figure for cagrilintide. The 22.7% belongs to both drugs together.
3. Assuming an amylin drug helps blood sugar. Pooled analysis found no meaningful change in HbA1c on cagrilintide monotherapy.
4. Comparing across trials when a within-trial comparison exists. This is one of the few pairs where it does.
5. Reading investigational as nearly available. Cagrilintide has never been approved as a single agent anywhere.
6. Ignoring the outcome data. One of these two has prevented cardiovascular events in a trial of 17,604 people.