Chronic weight management in adults with obesity
Amount
Up to 24 mg (with dose escalation)
Frequency
Once weekly
Duration
48 weeks (Phase 2)
Route
SCSchedule
Once weekly
Timing
Dose escalation from lower starting dose to maintenance dose to mitigate GI adverse events. Same day each week.
Duration
48 weeks (Phase 2); Phase 3 planned
Repeatable
Yes
Fasting glucose and HbA1c
When: Baseline and every 12 weeks
Why: Monitor glycemic effects
Lipid panel
When: Baseline and 12 weeks
Why: Assess metabolic parameters
Liver function tests (ALT, AST)
When: Baseline and 12 weeks
Why: Monitor hepatic function
CBC with differential
When: Baseline
Why: Baseline blood cell counts
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CT-388 (also known as RO7795068) is a signal-biased dual glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptor agonist developed by Roche/Genentech. Roche acquired CT-388 through its $2.7 billion acquisition of Carmot Therapeutics in 2023.
CT-388 is distinguished from other dual GLP-1/GIP agonists by its biased signaling profile. It was designed to have potent activity at both GLP-1 and GIP receptors while minimizing beta-arrestin recruitment at both receptors. This minimizes receptor internalization and desensitization, which preclinical data suggests leads to prolonged pharmacological activity compared to balanced agonists.
In Phase 2, weekly subcutaneous CT-388 at 24 mg achieved 22.5% placebo-adjusted weight loss at 48 weeks in 469 adults with obesity, with no plateau observed. These results position CT-388 among the most effective anti-obesity therapies in clinical development.
CT-388 activates both GLP-1 and GIP receptors with a unique signaling profile:
Signal-biased dual agonism:
GLP-1 receptor activation:
GIP receptor activation:
The biased signaling mechanism is the key differentiator. Standard GLP-1/GIP agonists activate both the cAMP (G-protein) and beta-arrestin signaling pathways. Beta-arrestin recruitment leads to receptor internalization and desensitization, reducing drug effectiveness over time. CT-388's minimal beta-arrestin coupling may maintain receptor availability on the cell surface, allowing sustained cAMP signaling.
In Phase 1b, CT-388 achieved 18.8% placebo-adjusted weight loss at 24 weeks, with 100% of treated participants achieving at least 5% weight loss and 45% achieving at least 20%.
The Phase 2 trial enrolled 469 adults with obesity or overweight and evaluated three subcutaneous dose levels of CT-388 versus placebo over 48 weeks.
Key results at the highest dose (24 mg):
CT-388 improved glycemic control in mice and monkeys, reduced body weight, suppressed appetite, and improved metabolic dysfunction-associated steatohepatitis (MASH) pathology in mice.
Roche has announced plans to initiate two Phase 3 trials in Q1 2026.
Effects of CT-388, a once-weekly signaling-biased dual GLP-1/GIP receptor agonist, on weight loss and glycemic control in preclinical models and participants with obesity, published in Cell Metabolism (Roche/Genentech/Carmot Therapeutics investigators, 2025; PMID: 41319798):
Phase 2 Trial of CT-388 in Adults with Obesity, published in Roche press release / conference presentation (Roche/Genentech investigators, 2026):
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0View community protocolsTirzepatide: FDA-approved dual GIP/GLP-1 agonist with up to 22.5% weight loss. Covers SURPASS/SURMOUNT trials, dosing, and semaglutide comparison.
Semaglutide: FDA-approved GLP-1 agonist for weight loss and diabetes. Covers STEP/SUSTAIN trials, Ozempic vs Wegovy dosing, and cardiovascular benefits.
VK2735: dual GLP-1/GIP agonist by Viking Therapeutics. Phase 2 showed 14.7% weight loss in 13 weeks. SC and oral formulations. Phase 3 VANQUISH underway.
Retatrutide: Triple GIP/GLP-1/glucagon agonist with up to 24% weight loss. Covers mechanism, Phase 2/3 trial data, dosing, and side effects.
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Retatrutide holds a clear advantage in both efficacy and development timeline. Its triple-receptor mechanism produced 28.7% weight loss in Phase 3 -- substantially greater than CT-388's 22.5% in Phase 2 -- and it is approximately 2-3 years ahead in the regulatory pathway. However, this superior efficacy comes at a cost: higher GI side effect rates and a novel dysesthesia safety signal. CT-388's signaling-biased approach offers a potentially better-tolerated dual agonist with impressive Phase 2 results and no plateau at 48 weeks. For patients who cannot tolerate triple agonist side effects, CT-388 may eventually represent a compelling alternative. Both remain investigational and are not available outside clinical trials.
Tirzepatide remains the proven standard with FDA approval, extensive phase 3 data, and commercial availability. CT-388 is a compelling next-generation competitor with a novel signaling-biased mechanism that produced 22.5% weight loss in phase 2 at 48 weeks -- potentially competitive with tirzepatide's 20.9% at 72 weeks in SURMOUNT-1. CT-388's key innovation is minimizing beta-arrestin-mediated receptor desensitization, which may explain the sustained weight loss trajectory observed. However, CT-388 must still complete phase 3 trials to confirm these results in larger populations.
A comprehensive guide to every GLP-1 receptor agonist drug, from FDA-approved semaglutide and tirzepatide to pipeline therapies like retatrutide, amycretin, MariTide, and oral orforglipron.
Every GLP-1 and incretin drug ranked by clinical weight loss data as of 2026, from retatrutide at 28.7% to oral orforglipron at 11.2%, with comparison tables and trial details.
A comprehensive comparison of GI side effects across GLP-1 drugs, from semaglutide and tirzepatide to next-generation biased agonists like ecnoglutide and CT-388 that may improve tolerability.
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