Cagrilintide vs Retatrutide
A long-acting amylin analogue given once weekly. Alone it produced up to 10.8% weight loss over 26 weeks against 3.0% on placebo [1]; the 20.4% figure people quote is the CagriSema combination with semaglutide, not cagrilintide on its own [3]. Not approved anywhere — the combination is under FDA review.
The world's first triple-action weight loss peptide that simultaneously activates three hormone receptors—GIP, GLP-1, and glucagon—delivering unprecedented weight loss results of up to 24% body weight in clinical trials [1][2].
Written by Michael Carroll — Owner, Director of Research · Reviewed by the Peptide Initiative Research Team · Editorial standards
Quick comparison
Dose range
Cagrilintide
0.3–4.5 mg
Retatrutide
4–8 mg
Frequency
Cagrilintide
Once weekly
Retatrutide
Once weekly
Administration
Cagrilintide
Subcutaneous injection
Retatrutide
Subcutaneous injection
Cycle length
Cagrilintide
Continuous — trials ran 26 to 68 weeks with no planned stop
Retatrutide
12+ weeks
Onset speed
Cagrilintide
Gradual (3-4 weeks)
Retatrutide
Moderate (1-2 weeks)
Evidence level
Cagrilintide
Strong human trials (Phase 3 or FDA approved)
Retatrutide
Moderate human trials (Phase 1-2)
Benefit ratings
Appetite Control
Weight Loss
GLP-1 Synergy
Weight Loss Power
Metabolic Health
Compound specifications
Cagrilintide
Molecular formula
C194H312N54O59S2
Molecular weight
4409 g/mol
Half-life
159-195 hours (~7-8 days)
Bioavailability
~100% (subcutaneous)
CAS number
1415456-99-3
Retatrutide
Molecular formula
C221H342N46O68
Molecular weight
4731 g/mol
Half-life
~6 days (allows once-weekly dosing)
Bioavailability
High via subcutaneous injection
CAS number
2381089-83-2
Dosing compared
Cagrilintide
Subcutaneous
0.3 mg
Once weekly · 26 weeks in the dose-finding trial
The lowest dose studied as monotherapy. Roughly 100 participants took it for 26 weeks; the cagrilintide groups as a whole lost 6.0% to 10.8% of body weight against 3.0% on placebo, with 0.3 mg at the bottom of that range [1]. Participants reached their assigned dose through an escalation period of up to 6 weeks; in the combination trials cagrilintide and semaglutide were co-escalated in 4-week steps over 16 weeks [2]. So there is a titration to your own target dose — there is not a ladder from one dose level to the next, because the dose groups ran in parallel and nobody crossed between them [1].
0.6 mg
Once weekly · 26 weeks in the dose-finding trial
A studied dose level, about 100 participants, 26 weeks [1]. Also one of the six cagrilintide doses tested alongside semaglutide 2.4 mg in the phase 1b trial [2].
1.2 mg
Once weekly · 26 weeks alone; 20 weeks in combination
In combination with semaglutide 2.4 mg this dose produced 15.7% weight loss at 20 weeks against 9.8% for semaglutide plus placebo — about 6 points of additional loss attributable to cagrilintide [2].
2.4 mg
Once weekly · 26 to 68 weeks depending on the trial
The dose that went forward. Every phase 3 trial uses 2.4 mg, both alone and as half of the fixed-dose CagriSema combination: REDEFINE 1 in 3,417 adults with obesity [3], REDEFINE 2 in 1,206 adults with type 2 diabetes [6], and REIMAGINE 2 in 2,713 people with type 2 diabetes, which carried a cagrilintide 2.4 mg monotherapy arm of 152 [7]. In the phase 1b trial 2.4 mg with semaglutide gave 17.1% weight loss at 20 weeks against 9.8% on semaglutide plus placebo [2]. Participants reached their assigned dose through an escalation period of up to 6 weeks; in the combination trials cagrilintide and semaglutide were co-escalated in 4-week steps over 16 weeks [2]. So there is a titration to your own target dose — there is not a ladder from one dose level to the next, because the dose groups ran in parallel and nobody crossed between them [1].
4.5 mg
Once weekly · 26 weeks in the dose-finding trial
The highest dose ever given to humans, and the top of the monotherapy dose-response: 10.8% weight loss (11.5 kg) at 26 weeks against 3.0% (3.3 kg) on placebo, and against 9.0% (9.6 kg) for liraglutide 3.0 mg — a 1.8 percentage point edge over liraglutide, p=0.03 [1]. It was not the dose taken into phase 3. A dedicated cardiac study escalated 53 healthy participants to 4.5 mg and found no clinically relevant QTc prolongation against placebo [8].
Retatrutide
Subcutaneous
Weeks 1-4
2 mg
Once weekly · Weeks 1-4 (then escalate 2 mg every 4 weeks)
Phase 2 obesity trial initiated higher-dose arms at 2 mg weekly with stepwise 2 mg increases every 4 weeks to limit GI effects [1].
Maintenance after titration
4-8 mg
Once weekly · Maintenance after titration
Mid-range maintenance doses; 8 mg produced ~22% mean weight loss at 48 weeks in the phase 2 trial [1][3].
Maintenance (highest studied)
12 mg
Once weekly · Maintenance (highest studied)
Highest studied dose; produced ~24% mean weight reduction at 48 weeks [1]. Still investigational (not FDA-approved).
Best suited for
Cagrilintide
Weight loss and appetite control
Cagrilintide excels at reducing hunger by mimicking amylin, a hormone your pancreas naturally releases after meals. Phase 2 trials showed people losing up to 10.8% of body weight with cagrilintide alone - and that's without combining it with other medications.
Boosting GLP-1 medication results
When you hit a plateau with semaglutide or want even better results, cagrilintide adds a second satiety pathway. The CagriSema combination achieved over 20% weight loss in clinical trials - significantly more than either drug alone.
People who want once-weekly convenience
Unlike older amylin medications that required three daily injections, cagrilintide's extended half-life of about a week means you only inject once weekly. Set a reminder on your phone and you're done.
Those seeking natural-feeling appetite reduction
Cagrilintide works by enhancing your body's own fullness signals rather than forcing you to eat less. Many users report feeling genuinely satisfied with smaller meals rather than fighting willpower battles.
Metabolic health improvement
Beyond weight loss, cagrilintide helps with blood sugar control and metabolic markers. It slows stomach emptying and reduces post-meal glucose spikes, making it valuable for people with or at risk for type 2 diabetes.
Retatrutide
Significant Obesity Management
If you need to lose a substantial amount of weight, retatrutide is showing unprecedented results. Phase 2 trials demonstrated average weight loss of 24% at the highest dose—that's nearly 60 pounds for someone weighing 250 lbs [1]. No other medication has matched this [1].
Type 2 Diabetes with Obesity
Retatrutide tackles both problems at once. It dramatically improves blood sugar control (HbA1c reductions of up to 2%) while delivering major weight loss [6]. The dual benefit makes it especially valuable for diabetics struggling with weight.
Metabolic Syndrome Warriors
If you're dealing with the cluster of issues that includes high blood sugar, excess belly fat, abnormal cholesterol, and high blood pressure, retatrutide's triple mechanism attacks multiple aspects of metabolic dysfunction simultaneously [5].
Fatty Liver Disease (MASLD)
Early research shows retatrutide may significantly reduce liver fat [7]. For people with non-alcoholic fatty liver disease, this peptide offers hope through weight loss plus direct metabolic improvements that benefit liver health.
Side effects
Cagrilintide
Common
- Nausea
- Constipation
- Diarrhea
- Injection site reactions
Uncommon
- Vomiting
- Headache
Serious
- Severe allergic reactions
Retatrutide
Common
- Nausea
- Diarrhea
- Constipation
- Decreased appetite
Uncommon
- Increased heart rate
- Injection site reactions
Serious
- Pancreatitis
- Gallbladder problems
Safety & evidence
Cagrilintide
Evidence level
Strong human trials (Phase 3 or FDA approved)
FDA status
Not approved anywhere. Cagrilintide alone is not in any regulatory filing; the fixed-dose CagriSema combination with semaglutide was submitted to the FDA on 18 December 2025 and is under review.
Safety overview
Gastrointestinal effects are the dominant finding and they are common, not rare. In the 26-week dose-finding trial, gastrointestinal adverse events occurred in 41% to 63% of cagrilintide participants across the dose groups against 32% on placebo, with nausea in 20% to 47% against 18%; 73 of 906 participants (10%) stopped treatment permanently and 30 (4%) did so because of adverse events [1]. In the 68-week phase 3 obesity trial the combination with semaglutide produced gastrointestinal adverse events in 79.6% against 39.9% on placebo, mainly transient and mild to moderate [3]; in the type 2 diabetes phase 3 the figures were 72.5% against 34.4% [6]. In the 2,713-person REIMAGINE 2 trial, adverse events were reported by 82.2% (125 of 152) of those on cagrilintide 2.4 mg alone against 70.5% (105 of 149) on placebo [7]. A dedicated cardiac study in 105 healthy participants found no clinically relevant QTc prolongation at the highest studied dose of 4.5 mg against placebo [8].
Contraindications
- Pregnancy or breastfeeding — no human data
- Known hypersensitivity to cagrilintide or any excipient
- There is no approved label, so there is no authoritative contraindication list — everything here is inferred from trial exclusion criteria and the amylin class
Retatrutide
Evidence level
Moderate human trials (Phase 1-2)
FDA status
Research compound
Safety overview
Retatrutide has shown a generally favorable safety profile in Phase 1 and Phase 2 clinical trials involving over 600 participants [1][6]. Most side effects are gastrointestinal and tend to improve over time [3]. The medication appears well-tolerated when doses are increased gradually. No major safety signals have emerged, but larger Phase 3 trials are still ongoing [3].
Contraindications
- Personal or family history of medullary thyroid carcinoma (MTC)
- Multiple Endocrine Neoplasia syndrome type 2 (MEN 2)
- Pregnancy or planning to become pregnant
- History of severe pancreatitis
- Known allergy to GLP-1 receptor agonists
Which is right for you?
Choose Cagrilintide if...
- Weight loss
- Appetite control
- Metabolic health
- GLP-1 augmentation
Choose Retatrutide if...
- Significant weight loss
- Type 2 diabetes management
- Metabolic health improvement
- Body composition optimization