Key takeaways:
- CagriSema is a once-weekly mixture of semaglutide and cagrilinitide.
- For adults with obese or weight problems, weight reduction was as much as 22.7% in these with out diabetes and 13.7% in these with diabetes.
CHICAGO — The mix of once-weekly cagrilintide 2.4 mg and semaglutide 2.4 mg conferred better weight reduction at 68 weeks in contrast with placebo in sufferers with obese or weight problems with or with out diabetes, researchers reported.
Outcomes of the REDEFINE 1 trial evaluating cagrilintide/semaglutide (CagriSema, Novo Nordisk) with placebo in sufferers with obese or weight problems and the REDEFINE 2 trial evaluating CagriSema with placebo in sufferers with weight problems and sort 2 diabetes had been introduced on the American Diabetes Affiliation Scientific Periods and concurrently printed in The New England Journal of Drugs.
“[CagriSema] is a mixture of a GLP-1 and an amylin analog,” Melanie J. Davies, CBE, MB, ChB, MD, FRCP, FRCGP, professor of diabetes drugs on the College of Leicester, United Kingdom, who introduced the outcomes of REDEFINE 2, informed Healio. “Amylin analogs have been round, however not a long-acting one like this. We had been wanting to have a look at the results on weight and, in REDEFINE 2, glycemic management.”
REDEFINE 1
For REDEFINE 1, resesarchers randomly assigned in a 21:3:3:7 ratio 3,417 contributors with obese or weight problems however with out diabetes (imply age, 47 years; 67.6% girls) to obtain subcutaneous administration of CagriSema, semaglutide 2.4 mg alone (Wegovy, Novo Nordisk), cagrilintide 2.4 mg alone or placebo, respectively. All had a BMI of 30 kg/m2 or better or 27 kg/m2 or better with a minimum of one obesity-related complication. The first outcomes had been change in physique weight and proportion of sufferers with a minimum of 5% discount of physique weight at 68 weeks.
At 68 weeks, the estimated imply % change in physique weight was –20.4% within the CagriSema group in contrast with –3% within the placebo group (estimated distinction, –17.3 proportion factors; 95% CI, –18.1 to –16.6; P < .001), in accordance with W. Timothy Garvey, MD, FACE, MABOM, endocrinologist and professor on the College of Alabama (UAB) at Birmingham and principal investigator of the UAB Diabetes Analysis Middle.
Common weight reduction at 68 weeks was 11.5% within the cagrilintide-only group and 14.9% within the semaglutide-only group.
W. Timothy Garvey
Amongst contributors who had been totally adherent to their routine, imply weight reduction was –22.7% within the CagriSema group, and 40.4% of contributors assigned CagriSema who had been totally adherent misplaced a minimum of 25% of physique weight at 68 weeks.
In contrast with the placebo group, the CagriSema group extra typically achieved weight lack of 5%, 20%, 25% and 30% at 68 weeks (P < .001 for all), Garvey and colleagues discovered.
The share of contributors who achieved a minimum of 25% weight reduction was 34.7% within the CagriSema group, 14.8% within the semaglutide group and 6.5% within the cagrilintide group, whereas the share that achieved a minimum of 30% weight reduction was 19.3% within the CagriSema group, 8.7% within the semaglutide group and 1.6% within the cagrilintide group, in accordance with the researchers.
Systolic blood stress fell –9.9 mm Hg within the CagriSema group in contrast with –3.2 mm Hg within the placebo group (estimated between-group distinction, 6.7 mm Hg; 95% CI, 7.8 to five.6; P < .001) and diastolic BP fell –5.1 mm Hg within the CagriSema group and –1.9 mm Hg within the placebo group (estimated between-group distinction, 3.2 mm Hg; 95% CI, 3.9 to 2.5), in accordance with Garvey and colleagues. The researchers additionally discovered that the CagriSema group had better modifications in HbA1c, glucose, insulin, lipid and C-reactive protein ranges than the placebo group.
In contributors with prediabetes, 87.7% of the CagriSema group and 32.2% of the placebo group achieved normoglycemia by 68 weeks.
The prevalence of gastrointestinal uncomfortable side effects corresponding to nausea, vomiting, diarrhea, constipation, stomach ache or hepatobiliary situations was 79.6% within the CagriSema group and 39.9% within the placebo group, with most occasions being delicate to average and non permanent, the researchers discovered.
REDEFINE 2
For REDEFINE 2, Davies and colleagues randomly assigned in a 3:1 ratio 1,206 contributors with a BMI of 27 kg/m2 or better and sort 2 diabetes with an HbA1c of seven% to 10% to obtain CagriSema or placebo, respectively. The first endpoints had been the identical as in REDEFINE 1.
The imply age was 55.9 years within the CagriSema group and 56.5 years within the placebo group. Girls comprised 47.5% of the CagriSema group and 46.4% of the placebo group.
At 68 weeks, within the remedy coverage estimand, the estimated imply % change in physique weight was –13.7% within the CagriSema group in contrast with –3.4% within the placebo group (estimated distinction, –10.4 proportion factors; 95% CI, –11.2 to –9.5; P < .001), in accordance with the researchers. For the trial-product estimand, the estimated imply % change in physique weight was –15.7% within the CagriSema group and –3.1% within the placebo group (estimated distinction, –12.6 proportion factors; 95% CI, –13.4 to –11.7), Davies and colleagues reported.
Members within the CagriSema group had been extra probably than these within the placebo group to attain weight lack of 5% (83.6% vs. 30.8%) and 20% (22.9% vs. 0.5%) at 68 weeks (P < .001 for each), the researchers discovered.
Modifications in waist circumference and BMI additionally favored the CagriSema group, in accordance with Davies and colleagues.
“The agent was capable of obtain strong and clinically significant weight reduction in sufferers with kind 2 diabetes,” Davies informed Healio. “In previous research, the load loss we see in sufferers with kind 2 diabetes is round 30% to 40% lower than we see in folks with out diabetes. So 13.7% is amongst the perfect we’ve ever seen with a remedy, by way of weight reduction, in kind 2 diabetes.”
The CagriSema group had better discount in HbA1c than the placebo group within the treatment-policy estimand (–1.8 proportion factors vs. –0.4 proportion factors; estimated distinction, –1.4; 95% CI, –1.6 to –1.2; P < .001), Davies and colleagues discovered.
An HbA1c of 6.5% or much less at 68 weeks was achieved by 73.5% of the CagriSema group and 15.9% of the placebo group, in accordance with the researchers.
For the 199 contributors with steady glucose monitoring, the imply proportion of time spent within the glycemic goal vary at 86 weeks was 86.8% within the CagriSema group and 50.2% within the placebo group; each teams had been beneath the goal vary lower than 1% of the time, in accordance with Davies and colleagues.
Change in systolic BP at 68 weeks favored the CagriSema group (estimated distinction, –4.1 mm Hg; 95% CI, –6 to –2.1; P < .001), as did modifications in diastolic BP, C-reactive protein and lipids, the researchers discovered.
Gastrointestinal adversarial occasions occurred in 72.5% of the CagriSema group and 34.4% of the placebo group, and most occasions had been delicate to average and non permanent, in accordance with the outcomes.
“We’ve obtained very highly effective brokers which can be capable of decrease HbA1c and weight in sufferers with kind 2 diabetes,” Davies informed Healio. “These outcomes are amongst the perfect we’ve ever seen. That is the second dual-approach agent after tirzepatide (Mounjaro/Zepbound, Eli Lilly) to point out actually good outcomes. What units [CagriSema] aside is the mechanism of motion, with the amylin analog. Within the steady glucose monitoring subgroup, we noticed it was very efficient from a glycemic management perspective.”
The outcomes on BP and different cardiovascular threat elements had been encouraging, and “we haven’t seen it in human research but, however we all know that it could impression on the metabolic adaptation that we see,” Davies informed Healio. “It does appear to have an impression on vitality expenditure that maybe the opposite brokers don’t have, and a theoretical profit on physique composition and bone. We’ll see if that bears out sooner or later.”
References:
For extra info:
Melanie J. Davies, MD, might be reached at melanie.davies@uhl-tr.nhs.uk.
Sources/Disclosures
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Garvey WT, et al. Symposium – Efficacy and security of CagriSema 2.4 mg/2.4 mg in adults with obese/weight problems —The REDEFINE 1 and REDEFINE 2 scientific trials. Offered at: American Diabetes Affiliation Scientific Periods; June 20-23, 2025; Chicago.
Disclosures:
The REDEFINE 1 and a pair of research had been funded by Novo Nordisk. Davies stories monetary ties with AbbVie, Amgen, AstraZeneca, Boehringer Ingelheim, Eli Lilly, GlaxoSmithKline, Novo Nordisk, Pfizer, Regeneron, Roche, Sanofi and Zealand. Garvey stories monetary ties with Alnylam, Boehringer Ingelheim, Eli Lilly, F. Hoffman-La Roche, Fractyl Well being, Gan & Lee Prescribed drugs USA, Imogen, Keros, Neurocrine Biosciences, Novo Nordisk, Pfizer, Regeneron and Zealand. Please see the research for all different authors’ related monetary disclosures.
