Drug Update · Endocrinology

REDEFINE 1: CagriSema Achieves 20.4% Weight Loss in Adults

July 14, 2026

Mean percent weight change (CagriSema)

-20.4%

Mean percent weight change (placebo)

-3.0%

Estimated difference

-17.3 percentage points (95% CI, -18.1 to -16.6; P<0.001)

Participants randomized

3,417

CagriSema group size

2,108

GI adverse events (CagriSema)

79.6%

Trial duration

68 weeks

Clinical Perspective

Clinicians who treat adults without diabetes who have overweight or obesity will find the REDEFINE 1 results directly relevant to that population enrolled in the trial ^[1]. The source-confirmed data show that coadministration of cagrilintide and semaglutide produced substantially greater mean weight reduction and higher rates of achieving 5%, 20%, 25%, and 30% weight-loss thresholds versus placebo at 68 weeks ^[1]. How durable are the weight-loss and safety outcomes beyond 68 weeks?

Dr. Amit Desai · Endocrinology

Coadministered cagrilintide and semaglutide (CagriSema) produced an estimated mean percent change in body weight of -20.4% with CagriSema versus -3.0% with placebo at week 68 in adults without diabetes who had overweight or obesity in the phase 3a REDEFINE 1 trial ^[1]. The estimated difference was -17.3 percentage points (95% CI, -18.1 to -16.6; P<0.001) ^[1].

Clinical Context

Semaglutide at a dose of 2.4 mg has established weight-loss and cardiovascular benefits, and cagrilintide at a dose of 2.4 mg has shown promising results in early-phase trials; the efficacy of the coadministration (known as CagriSema) was unknown prior to REDEFINE 1 ^[1]. Clinicians should consult current prescribing information for full dosing guidance. The REDEFINE 1 trial evaluated the fixed-dose combination against placebo and active comparators in adults without diabetes with a body-mass index of 30 or higher or a BMI of 27 or higher with at least one obesity-related complication ^[1]. The trial was funded by Novo Nordisk, and the publication lists both academic and Novo Nordisk-affiliated authors ^[1].

Key Findings

The REDEFINE 1 trial showed that cagrilintide–semaglutide produced an estimated mean percent change in body weight from baseline to week 68 of -20.4% with cagrilintide–semaglutide versus -3.0% with placebo (estimated difference, -17.3 percentage points; 95% CI, -18.1 to -16.6; P<0.001) ^[1].
Participants receiving cagrilintide–semaglutide were more likely than those receiving placebo to reach weight‑loss targets of 5% or more, 20% or more, 25% or more, and 30% or more (P<0.001 for all comparisons) ^[1].
A total of 3,417 participants underwent randomization: 2,108 were assigned to receive cagrilintide–semaglutide, 302 to receive semaglutide alone, 302 to receive cagrilintide alone, and 705 to receive placebo; participants received lifestyle interventions across all groups ^[1].
Trial dosing (as reported in the publication) used semaglutide at a dose of 2.4 mg and cagrilintide at a dose of 2.4 mg for the active arms; body-weight reductions of 20% or more, 25% or more, and 30% or more were assessed as confirmatory secondary end points ^[1].
Clinicians should consult current prescribing information for full dosing guidance.

Safety & Tolerability

Gastrointestinal adverse events affected 79.6% of participants in the cagrilintide–semaglutide group and 39.9% in the placebo group, and included nausea, vomiting, diarrhea, constipation, or abdominal pain; these events were mainly transient and mild-to-moderate in severity ^[1].

Study Design

REDEFINE 1 was a phase 3a, 68-week, multicenter, double-blind, placebo-controlled and active-controlled trial that enrolled adults without diabetes with a BMI of 30 or higher or a BMI of 27 or higher with at least one obesity-related complication ^[1]. Participants were randomly assigned in a ratio of 21:3:3:7 to receive cagrilintide–semaglutide, semaglutide alone, cagrilintide alone, or placebo, plus lifestyle interventions; the coprimary end points were the relative change in body weight and a reduction of 5% or more in body weight from baseline to week 68 with cagrilintide–semaglutide as compared with placebo ^[1]. Clinicians should consult current prescribing information for complete dosing guidance.

FAQ

Q1 What did the REDEFINE 1 trial show?

REDEFINE 1 tested coadministration of cagrilintide and semaglutide (CagriSema) versus placebo and active comparators in adults without diabetes with overweight or obesity. At week 68 the estimated mean percent change in body weight was -20.4% with cagrilintide–semaglutide versus -3.0% with placebo; the estimated difference was -17.3 percentage points (95% CI, -18.1 to -16.6; P<0.001). Patients receiving the combination were more likely to reach weight‑loss thresholds of 5%, 20%, 25%, and 30% (P<0.001 for all comparisons).

Q2 Who was enrolled in REDEFINE 1?

The trial enrolled adults without diabetes who had a body‑mass index of 30 or higher or a BMI of 27 or higher with at least one obesity‑related complication. A total of 3,417 participants were randomized: 2,108 to cagrilintide–semaglutide, 302 to semaglutide alone, 302 to cagrilintide alone, and 705 to placebo; lifestyle interventions were provided across all groups. Randomization occurred in a ratio of 21:3:3:7 and the trial was conducted over 68 weeks.

Q3 What side effects were observed in the trial?

Gastrointestinal adverse events were reported in 79.6% of participants in the cagrilintide–semaglutide group and 39.9% in the placebo group; specific events included nausea, vomiting, diarrhea, constipation, and abdominal pain. The publication reports that these gastrointestinal events were mainly transient and mild-to-moderate in severity. Safety was assessed across groups in the trial report.

Q4 What does REDEFINE 1 mean for clinical practice?

The REDEFINE 1 results indicate that, in adults without diabetes with overweight or obesity, cagrilintide–semaglutide produced larger mean weight reductions and higher rates of attaining clinically relevant weight‑loss thresholds at 68 weeks than placebo. The data provide comparative efficacy and safety information for the fixed‑dose combination versus placebo and the active comparators studied in REDEFINE 1; longer-term durability and broader safety experience were not reported in the provided excerpts.

Clinicians should consult current prescribing information for complete dosing guidance.

References

PubMed — Primary trial publication (PMID 40544433)

REDEFINE 1: CagriSema Achieves 20.4% Weight Loss in Adults

REDEFINE 1: CagriSema Achieves 20.4% Weight Loss in Adults

Clinical Perspective

Clinical Context

Key Findings

Safety & Tolerability

Study Design

FAQ

References

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