Two ways of adding a second signal
The first generation of GLP-1 drugs used one hormone signal. The current race is about adding a second one, and CagriSema and tirzepatide represent the two main strategies.
Tirzepatide is a single 39 amino acid peptide engineered to activate two incretin receptors at once: GLP-1 and GIP. Both are gut hormones released after meals; both raise glucose-dependent insulin release. One molecule, two receptors, one weekly injection.
CagriSema keeps semaglutide as its GLP-1 half and adds a different hormone entirely. Cagrilintide is a long-acting analogue of amylin, which the pancreas releases alongside insulin and which signals fullness through receptors in the hindbrain. Two separate peptides, co-formulated at 2.4 mg each, in one weekly injection.
Both companies bet that two satiety signals beat one. The direct trial between them, reported in February 2026, is one of the few places where the bets have been compared on the same people.
Side by side
| CagriSema | Tirzepatide Stocked locally | |
|---|---|---|
| Structure | Two peptides: cagrilintide 2.4 mg + semaglutide 2.4 mg | One peptide, 39 amino acids, C20 fatty diacid chain |
| Receptors | Amylin + GLP-1 | GIP + GLP-1 |
| Dosing | Weekly | Weekly |
| Half-life | Semaglutide about 1 week; cagrilintide long-acting | About 5 days |
| Pivotal obesity trial | REDEFINE 1: 20.4% vs 3.0% at 68 weeks (all randomised) | SURMOUNT-1: 20.9% (15 mg) vs 3.1% at 72 weeks (all randomised) |
| Head-to-head (REDEFINE 4, 84 weeks) | 20.2% all randomised; 23.0% on treatment | 23.6% all randomised; 25.5% on treatment |
| GI adverse events in pivotal trial | 79.6% vs 39.9% placebo | Most common event class; mostly mild to moderate |
| Regulatory status (Sep 2026) | Filed with US FDA December 2025; not approved anywhere | Approved (Mounjaro 2022, Zepbound 2023) |
| Philippines | Not registered | Mounjaro on prescription at Watsons and Rose |
The pivotal trials, separately
REDEFINE 1 (2025) enrolled 3,417 adults with obesity or overweight and no diabetes for 68 weeks, randomised 21:3:3:7 to CagriSema, semaglutide alone, cagrilintide alone or placebo. Counting everyone randomised regardless of whether they kept taking it, mean weight change was 20.4% on CagriSema versus 3.0% on placebo, a 17.3 point difference. Gastrointestinal adverse events affected 79.6% on CagriSema and 39.9% on placebo, and were described as mainly transient and mild to moderate.
SURMOUNT-1 (2022) enrolled 2,539 adults with obesity or overweight and no diabetes for 72 weeks, including a 20-week escalation. Mean weight change was 15.0%, 19.5% and 20.9% on 5, 10 and 15 mg, against 3.1% on placebo. 57% of the 15 mg group lost 20% or more of body weight, against 3% on placebo. Adverse events led to discontinuation in 4.3%, 7.1% and 6.2% across the three doses versus 2.6% on placebo.
On paper, then, the two pivotal results look nearly identical: 20.4% and 20.9% by the same intention-to-treat logic, in similar populations over similar durations. That apparent tie is exactly why a direct trial was needed.
The direct trial: REDEFINE 4
REDEFINE 4 randomised 809 adults with obesity and at least one comorbidity to CagriSema 2.4/2.4 mg or tirzepatide 15 mg, both weekly, for 84 weeks. It was open label: participants and investigators knew who was on what. The primary endpoint was non-inferiority of CagriSema on weight loss.
Novo Nordisk reported the topline in February 2026:
- Counting everyone randomised: 20.2% on CagriSema, 23.6% on tirzepatide.
- Among those who stayed on treatment: 23.0% on CagriSema, 25.5% on tirzepatide.
- Primary endpoint: not met. CagriSema did not show non-inferiority to tirzepatide.
Novo described CagriSema's tolerability as consistent with its earlier trials, with gastrointestinal events that were mostly mild to moderate and diminished over time, and did not give discontinuation figures in the release. Full peer-reviewed results have not been published as of September 2026, so the numbers above come from the company.
Two cautions apply. An open-label design can shift behaviour in both arms, and the comparison used tirzepatide's top dose against CagriSema's only dose; Novo has said a higher-dose CagriSema trial would start in the second half of 2026. Even so, this is the class's clearest direct answer so far, and it went to the single-molecule dual agonist.
Why the pivotal trials looked equal and the direct trial did not
Cross-trial comparison hides differences that a head-to-head exposes: baseline weight, how many participants dropped out and how their missing data were handled, escalation schedules, and site and era effects. REDEFINE 1 and SURMOUNT-1 were run three years apart in different countries by different sponsors. Put the drugs in the same trial and a 3.4 point gap appeared on the all-randomised basis.
That is the general lesson of the semaglutide vs liraglutide comparison too: the STEP 8 head-to-head, not the separate pivotal trials, is what settled the question there.
Side effects reported
Both drugs sit inside the GLP-1 class profile. For CagriSema in REDEFINE 1: nausea 55% versus 12.6% on placebo, constipation 30.7% versus 11.6%, vomiting 26.1% versus 4.1%, with discontinuation for adverse events around 6% versus under 4%. For tirzepatide in SURMOUNT-1: gastrointestinal events most common, concentrated during escalation, with the discontinuation figures above. The Zepbound label carries the class boxed warning on thyroid C-cell tumours seen in rats and warnings on pancreatitis, gallbladder disease and severe gastrointestinal reactions, and says not to combine it with other GLP-1 agonists. Any approved CagriSema label would be expected to carry semaglutide's equivalent warnings. See the side effect management guide.
Status in the Philippines
Tirzepatide is an approved medicine, sold as Mounjaro on prescription at Watsons and Rose Pharmacy; no Philippine registration for Zepbound has been identified. Prescribing belongs with a licensed Philippine physician. Watsons prices checked on its own pages on 26 August 2026 ran from PHP 11,650 for the 2.5 mg pen to PHP 29,900 for 12.5 or 15 mg, each pen holding four weekly doses; the full table and the monthly arithmetic are on cost reality in the Philippines.
CagriSema is not approved in any country and not registered with FDA Philippines. Anything offered locally under the name is either a research-market product of unknown make-up or a home mix of separately bought cagrilintide and semaglutide, neither of which is what REDEFINE tested. Enforcement against unregistered GLP-1 sellers has been active in 2026: two arrests in Tondo on 13 May for selling unregistered tirzepatide online, and an NBI and FDA Philippines raid on a Pasig clinic on 27 May.
The wider race
Tirzepatide's 25.5% in REDEFINE 4 is itself now the benchmark others chase. Retatrutide, which adds a glucagon signal to GIP and GLP-1, reported 28.3% at 80 weeks in TRIUMPH-1 and is covered on GLP-3 and retatrutide explained; survodutide pairs GLP-1 with glucagon. None of those figures is a head-to-head against tirzepatide, and REDEFINE 4 is a reminder of how much that distinction matters.
Storage
Tirzepatide pens are refrigerated at 2 to 8°C and may sit at room temperature up to 30°C for 21 days, after which the pen must be discarded. CagriSema has no approved label and so no official instruction; the peptides it contains are handled like other GLP-1 peptides in research, at 2 to 8°C and never frozen. In Manila, 30°C is an ordinary afternoon, so a brownout plan and an insulated pouch for transport apply to either.
