CagriSema vs Retatrutide: Weight Loss Trials Compared

CagriSema vs Retatrutide at a Glance

CagriSema and retatrutide cannot be ranked against each other because no head-to-head clinical study exists and their clinical trials used different designs. Novo Nordisk tested CagriSema over 68 weeks in REDEFINE 1 and 84 weeks in REDEFINE 4. Eli Lilly tested retatrutide over 80 weeks in TRIUMPH-1. The two study programs enrolled distinct participant groups in separate clinical trials.

Dosing structures differ as well. CagriSema is a fixed-dose pairing of two separate agents delivered in a single weekly injection. Retatrutide was evaluated across three distinct dosage strengths. Furthermore, each trial program reported its own placebo response, with REDEFINE 1 observing a 2.3% placebo reduction while TRIUMPH-1 observed a 2.2% reduction. Because these percentages reflect trial averages rather than guaranteed individual outcomes, declaring one candidate drug superior based on cross-trial arithmetic is unreliable.

What Each Drug Is

CagriSema is an investigational fixed-dose combination of cagrilintide and semaglutide developed by Novo Nordisk. Each once-weekly subcutaneous dose combines cagrilintide, a long-acting amylin receptor agonist, with semaglutide, a long-acting glucagon-like peptide-1 (GLP-1) receptor agonist. Novo Nordisk submitted CagriSema to the FDA for chronic weight management in December 2025, supported by data from the REDEFINE 1 and REDEFINE 2 trials. Novo Nordisk stated that an FDA decision is anticipated by late 2026. No commercial price, official label, or clinical dosing guidance exists today.

Retatrutide is Eli Lilly's investigational triple agonist that activates the GLP-1, GIP and glucagon receptors. It is administered by injection. Retatrutide is not approved by the FDA for any therapeutic use and remains unavailable through commercial medical channels. Eli Lilly is evaluating the molecule in its ongoing TRIUMPH Phase 3 clinical program. Eli Lilly stated that additional readouts from the TRIUMPH-2 and TRIUMPH-3 studies will be shared later in 2026, without establishing a date for FDA submission.

Media outlets often describe retatrutide using the informal shorthand "GLP-3". That label is informal media phrasing rather than a recognised biological hormone or official regulatory class. See our guide on what GLP-3 means.

Can You Get Either One Today?

Neither CagriSema nor retatrutide is available to patients today because both medications remain unapproved investigational compounds. Neither compound has an FDA-approved prescribing label or established commercial pricing. Anyone who needs treatment now should ask a licensed clinician about approved options. To see how these pipeline candidates compare to approved treatments, readers can review our guides on CagriSema vs Wegovy, CagriSema vs Zepbound, retatrutide vs tirzepatide, and retatrutide vs semaglutide.

CagriSema vs Retatrutide Trial Results Side by Side

Clinical trial data demonstrates substantial average weight loss for both medications, but variations in study length and dosing prevent direct comparison. REDEFINE 1 was a Phase 3 trial. Published in the New England Journal of Medicine (NEJM) on 22 June 2025, it evaluated 3,417 adults with obesity or overweight and one or more comorbidities, without type 2 diabetes. Participants had a mean baseline BMI of 38 kg/m2. CagriSema produced a mean 22.7% weight loss at 68 weeks if all participants adhered to treatment, compared to 2.3% for placebo. Regardless of adherence, CagriSema achieved a 20.4% reduction versus 3.0% for placebo. 97.6% of participants on CagriSema lost at least 5% of their body weight under the full-adherence estimand, according to the REDEFINE 1 NEJM release.

REDEFINE 2 enrolled 1,206 adults. Over 68 weeks in adults with type 2 diabetes and overweight or obesity, CagriSema produced a 15.7% mean weight loss versus 3.1% for placebo under full adherence. REDEFINE 4 enrolled 809 adults. Novo Nordisk announced on 23 February 2026 that CagriSema did not meet its primary endpoint of non-inferiority to tirzepatide 15 mg. The trial was open-label. It ran for 84 weeks. Under full adherence, CagriSema achieved a 23.0% weight reduction compared to 25.5% for tirzepatide 15 mg. Under the treatment-regimen estimand, CagriSema delivered a 20.2% reduction compared to 23.6% for tirzepatide, as detailed in the Novo Nordisk REDEFINE 4 announcement.

Eli Lilly evaluated retatrutide in TRIUMPH-1. The trial enrolled 2,339 adults with obesity without type 2 diabetes over 80 weeks. Participants were randomised to receive 4 mg, 9 mg, or 12 mg of retatrutide or a placebo. According to the Lilly TRIUMPH-1 announcement, average weight loss was 19.0% (about 47.2 lb) with 4 mg, 25.9% (about 64.4 lb) with 9 mg, and 28.3% (about 70.3 lb) with 12 mg. Placebo lost 2.2% (about 5.5 lb). In the 12 mg cohort, 65.3% of participants reached a BMI below 30 kg/m2. You can also explore our summary of retatrutide Phase 3 results for further context.

Eli Lilly shared additional data from other Phase 3 trials in the same program. TRIUMPH-2 enrolled adults with type 2 diabetes. Over 80 weeks, retatrutide produced average weight reductions of 12.7% on 4 mg, 19.1% on 9 mg, and 20.8% on 12 mg, compared to 4.0% for placebo. In TRIUMPH-4, a 68-week trial in adults with obesity and knee osteoarthritis receiving the 12 mg dose, participants achieved an average weight loss of 28.7%. However, Eli Lilly has not published knee pain, joint stiffness, or physical function scores from that trial. Consequently, whether retatrutide relieves osteoarthritis pain remains unconfirmed.

The numbers cannot be ranked because published press releases evaluate different trials. Retatrutide participants had 80 weeks to lose weight in TRIUMPH-1, which provides 12 additional weeks of treatment compared to the 68-week REDEFINE 1 trial. Dosing protocols also differed. Retatrutide was evaluated up to a high 12 mg dose, whereas CagriSema was delivered at a single fixed concentration. Neither compound has ever been tested against the other in a shared trial protocol. The retatrutide estimand is not stated here, so check the Lilly TRIUMPH-1 announcement before setting it beside the CagriSema full-adherence figures.

Side Effects and What Is Not Known

CagriSema trials documented frequent gastrointestinal adverse reactions. In the REDEFINE 1 trial, gastrointestinal adverse events occurred in 79.6% of CagriSema participants compared to 39.9% in the placebo group. Nausea affected 55.0% of CagriSema patients versus 12.6% on placebo. Constipation occurred in 30.7% versus 11.6%, and vomiting occurred in 26.1% versus 4.1%. Novo Nordisk reported that these digestive events were mostly transient and mild to moderate in severity. Discontinuation of treatment due to adverse events was 6.0% with CagriSema compared to 3.7% with placebo. In REDEFINE 2, adverse event discontinuation reached 8.4% for CagriSema versus 3.0% for placebo.

Read the Lilly TRIUMPH-1 announcement and ask a clinician about tolerability. Top-line data from TRIUMPH-1 noted statistically significant improvements versus placebo in waist circumference, systolic blood pressure, non-high-density lipoprotein (non-HDL) cholesterol, triglycerides, and high-sensitivity C-reactive protein (hsCRP), but exact numerical changes are not published here.

Major clinical evidence gaps remain for retatrutide. Published trials have not evaluated its effects on chronic kidney disease, obstructive sleep apnea, or low back pain.

What Would Change the Comparison

Direct head-to-head clinical trials, FDA decisions, and published retatrutide safety data would change this comparison. A direct trial with matched study lengths, unified inclusion criteria, and identical endpoint definitions is necessary to determine whether one medication provides superior metabolic outcomes or better tolerability.

Regulatory actions will also clarify the landscape. Novo Nordisk anticipates an FDA decision on CagriSema by late 2026. For retatrutide, safety data is not given here and Lilly has stated no FDA submission date.

Verdict: Which One to Follow

We cannot name a better drug. Neither is approved for medical use. No trial has tested them against each other. When looking strictly at top-line figures, retatrutide achieved an average 28.3% weight loss at its highest 12 mg dose over 80 weeks in TRIUMPH-1. CagriSema produced a 22.7% mean loss at 68 weeks under full adherence in REDEFINE 1. However, differing trial lengths and dose designs make cross-trial ranking unreliable.

CagriSema has a submitted FDA application, with Novo Nordisk having submitted its application to the FDA in December 2025 and anticipating a decision by late 2026. However, it failed to demonstrate non-inferiority against tirzepatide 15 mg in the REDEFINE 4 trial. Retatrutide reached up to a 28.3% average weight loss in TRIUMPH-1 (80 weeks, 12 mg), but retatrutide safety data is not given here and Lilly has stated no FDA submission date.

If you are evaluating cagrisema vs retatrutide as future weight management options, speak with a licensed clinician about currently available treatments. Take our assessment.