Quick Comparison
| CT-388 | Tirzepatide | |
|---|---|---|
| Half-Life | Approximately 168 hours (7 days), supporting once-weekly dosing | 120 hours (5 days) |
| Typical Dosage | Phase 2 trials: doses up to 8 mg subcutaneous once weekly with stepwise escalation over 12-16 weeks. Phase 3 maintenance dosing being established. Higher and lower dose arms are being evaluated to balance weight loss against tolerability. | Weight management (Zepbound): 2.5 mg subcutaneous once weekly for 4 weeks, increasing by 2.5 mg every 4 weeks to maintenance dose of 5-15 mg once weekly. Diabetes (Mounjaro): same escalation schedule, maintenance 5-15 mg subcutaneous once weekly. |
| Administration | Subcutaneous injection (once weekly) | Subcutaneous injection (weekly) |
| Research Papers | 2 papers | 30 papers |
| Categories |
Mechanism of Action
CT-388
CT-388 is a once-weekly subcutaneous dual GLP-1/GIP receptor agonist, mechanistically similar to tirzepatide but with a distinct molecular structure designed for differentiated pharmacology. Activation of both receptors produces complementary metabolic effects: GLP-1 receptor agonism centrally suppresses appetite through hypothalamic and brainstem signalling, slows gastric emptying, and stimulates glucose-dependent insulin secretion from pancreatic beta cells, while GIP receptor agonism enhances beta-cell insulin response, modulates lipid handling in adipose tissue, and amplifies the central anorectic effect of GLP-1 through distinct hypothalamic neuronal circuits.
The molecule was engineered with a balanced potency profile across the two receptors and incorporates fatty acid acylation that enables strong albumin binding, extending half-life to approximately one week. This pharmacokinetic profile supports once-weekly subcutaneous dosing with stable plasma exposure across the dosing interval, which is associated with better gastrointestinal tolerability than less stable formulations that produce sharp peaks and troughs.
In the Phase 2 obesity trial of 469 participants, CT-388 produced up to 22.5% placebo-adjusted body weight reduction at 48 weeks at the highest dose. The weight-loss curve had not yet plateaued at the end of the trial, suggesting further reductions might be achievable with longer dosing. Roche acquired Carmot Therapeutics in late 2024 specifically to obtain CT-388, positioning it as their lead anti-obesity asset competing directly against tirzepatide and the next-generation Lilly and Novo Nordisk pipeline.
Tirzepatide
Tirzepatide is the first approved dual incretin receptor agonist, simultaneously activating both GIP (glucose-dependent insulinotropic polypeptide) and GLP-1 receptors. This dual mechanism represents a paradigm shift in obesity and diabetes treatment because the two receptor systems produce complementary and additive metabolic effects that neither achieves alone.
The GLP-1 receptor component works similarly to semaglutide — suppressing appetite through hypothalamic signaling, slowing gastric emptying, and stimulating glucose-dependent insulin secretion. However, the addition of GIP receptor agonism provides unique benefits. GIP receptors in adipose tissue enhance lipid metabolism and may improve fat storage efficiency, while GIP signaling in the brain appears to amplify the appetite-suppressing effects of GLP-1 through distinct neuronal circuits in the hypothalamus.
At the pancreatic level, the dual stimulation of both GIP and GLP-1 receptors on beta cells produces a more robust insulin secretory response than either pathway alone. Tirzepatide also improves insulin sensitivity in peripheral tissues, reduces hepatic fat content, and lowers triglyceride levels. The molecule is built on a modified GIP peptide backbone with GLP-1 receptor cross-reactivity, attached to a C20 fatty di-acid moiety that enables albumin binding and weekly dosing. Clinical trials have shown weight loss of up to 22.5% of body weight, surpassing GLP-1-only agents.
Risks & Safety
CT-388
Common
nausea, vomiting, diarrhea, constipation, decreased appetite, injection site reactions. Side-effect rates in Phase 2 were comparable to tirzepatide.
Serious
pancreatitis, gallstones, possible muscle mass loss, dehydration.
Rare
thyroid C-cell tumour class warning, severe allergic reactions. Long-term safety data not yet available.
Tirzepatide
Common
nausea (25-35%), diarrhea, constipation, vomiting, reduced appetite, stomach pain, redness at injection site.
Serious
inflammation of the pancreas (pancreatitis), gallstones, very slow stomach emptying (gastroparesis), low blood sugar if combined with other diabetes medications.
Rare
thyroid tumours seen in animal studies, severe allergic reactions, kidney problems.
Full Profiles
CT-388 →
Roche's once-weekly weight loss injection that targets the same two appetite hormones as tirzepatide (GLP-1 and GIP). Originally developed by Carmot Therapeutics before Roche acquired the company in 2024 specifically to obtain this molecule. In a Phase 2 trial of 469 people, it produced up to 22.5% placebo-adjusted body weight loss at 48 weeks — competitive with tirzepatide and showing no sign of plateau at the highest dose. Phase 3 trials started in 2026.
Tirzepatide →
Sold as Mounjaro and Zepbound, this is one of the most effective weight loss medications available. It works by targeting two appetite hormones at once (GIP and GLP-1), making it more powerful than medications like semaglutide that only target one. People in clinical trials lost up to 22.5% of their body weight. Also FDA-approved for type 2 diabetes, and improves cholesterol and blood fat levels.