A combined GLP-1 and amylin drug averaged about 21% weight loss at lower doses in a phase 3 trial
Edited by Samael A. Tejada, Founder & Editor-in-Chief
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CagriSema, a cagrilintide-plus-semaglutide combination, produced average weight loss of 20.7% and 21.0% at two lower dose levels versus 2.0% on placebo over 68 weeks in 309 adults without diabetes, Novo Nordisk reported from the phase 3 REDEFINE 9 trial (November 14, 2026). The drug is not approved in the US.
Two hormones, one injection, and a fifth of body weight gone in sixteen months — in a controlled trial. The numbers are strong; the questions this site asks of every weight-loss result — what happens to muscle, and what happens when treatment stops — remain for the follow-up data.
What did REDEFINE 9 test?
A randomised, double-blind, placebo-controlled phase 3b trial of CagriSema — the amylin analogue cagrilintide combined with the GLP-1 drug semaglutide — at 1.7 mg/1.7 mg and 1.0 mg/1.0 mg, in 309 adults with obesity (BMI at least 30) or overweight (BMI at least 27) with at least one obesity-related complication, without diabetes, over 68 weeks. The trial was not powered to compare the two doses against each other.
What were the results?
On the efficacy estimand, weight loss averaged 20.7% and 21.0% for the two doses versus 2.0% on placebo (treatment differences of about 19 percentage points, p<0.0001); on the treatment-regimen estimand, 19.4% and 18.6% versus 4.6%. Waist circumference fell by about 17 cm on treatment versus 3.6 cm on placebo, and roughly half of treated participants (51.3% and 48.3%) lost at least 20% of body weight, versus 2.7% on placebo. The most frequent adverse events were gastrointestinal, mild-to-moderate in severity; discontinuation for adverse events was 2.9% and 4.9% on treatment versus 4.9% on placebo.
Where does approval stand — and what is unanswered?
CagriSema is investigational and not approved in the US. Novo Nordisk filed for approval of the higher 2.4 mg/2.4 mg dose in December 2025, with an FDA decision expected in the fourth quarter of 2026. Unanswered by this release: body-composition detail — how much of the loss was fat versus lean tissue — and durability after stopping. Both matter for mitochondrial and metabolic health, because muscle is the body's largest glucose-burning, mitochondria-rich tissue; combination drugs that spare it would be a genuine advance, and the claim needs data, not inference.
Frequently asked questions
What is CagriSema?
A fixed combination of cagrilintide (an amylin analogue) and semaglutide (a GLP-1 receptor agonist) in one weekly injection, developed by Novo Nordisk for weight management. It is investigational and not approved in the US.
What is an efficacy estimand?
A statistical framing that estimates the effect if everyone stayed on treatment as directed. The treatment-regimen estimand — 19.4% and 18.6% here — includes people who stopped, and is usually the more conservative, real-world-flavoured number.
Why does a mitochondria site cover a weight-loss drug?
Because muscle is mitochondria-rich tissue and rapid weight loss can include lean mass. This site tracks what these drugs do to body composition and metabolic health — and reports plainly when that data has not been published, as here.
Where the evidence stands
- Established: GLP-1 medicines produce large, trial-proven weight loss, and amylin analogues act on complementary appetite pathways — the rationale for combining cagrilintide with semaglutide.
- Preliminary: CagriSema's lower-dose profile rests on this phase 3b trial's reported results; the drug remains investigational and unapproved in the US, and its regulatory decision is pending.
- Absent: Published body-composition (lean-mass) outcomes for CagriSema and any evidence on mitochondrial function — neither was reported with these results.
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