Roche’s CT-388 Dual Agonist Hits 22% Weight Loss—How It Compares
CT-388 reached placebo-adjusted weight loss of 22.5 % in Phase II. Explore key numbers, safety, and how it measures up to existing incretin therapies.
Roche’s CT-388 Dual Agonist Hits 22% Weight Loss — How It Compares
Featured snippet: In a January 2026 topline release, Roche reported that once-weekly CT-388 — a dual GLP-1/GIP receptor agonist — produced a placebo-adjusted 22.5 % weight loss at 48 weeks in adults with obesity, positioning the investigational drug as a potential rival to tirzepatide and high-dose semaglutide.(gene.com)
Last updated August 2026
- Drug class: Dual GLP-1/GIP receptor agonist (investigational)
- Highest Phase II dose: 24 mg once weekly for 48 weeks(gene.com)
- Placebo-adjusted weight loss: 22.5 % at 48 weeks(gene.com)
- Participants reaching ≥20 % loss: 47.8 % on 24 mg dose(gene.com)
- Study ID: NCT06525935 (ClinicalTrials.gov)(clinicaltrials.gov)
- Next step: Enith 1 & 2 Phase III trials starting 2H 2026(gene.com)
- CT-388 produced >22 % average weight loss at its highest Phase II dose — on par with or exceeding tirzepatide’s highest approved dose.
- The drug showed a clear dose-response relationship and no new safety signals versus other incretins.
- Phase III trials are slated for late 2026; FDA approval could follow by 2029 if outcomes stay positive.
- Because CT-388 biases signaling away from β-arrestin recruitment, it may sustain receptor activity longer — potentially translating into durable efficacy.
What Is CT-388 and How Does It Work?
CT-388 (enicepatide) is an investigational peptide that activates both the glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptors. These gut-derived hormones curb appetite, slow stomach emptying, and enhance insulin release. CT-388 was engineered to minimize β-arrestin recruitment, a cellular process that can internalize receptors and blunt their effects over time.(medically.gene.com)
By targeting both receptors with prolonged activity, CT-388 aims to drive greater and more sustained weight loss than single-pathway drugs such as semaglutide.
How Impressive Were the Phase II Results?
The 48-week, randomized, placebo-controlled CT388-103 study enrolled 469 adults with obesity or overweight plus at least one weight-related comorbidity. Participants received escalating weekly doses up to 24 mg or placebo. Key outcomes include:(gene.com)
| Endpoint | 24 mg CT-388 | Placebo | Placebo-Adjusted Difference |
|---|---|---|---|
| Percent weight change (efficacy estimand) | −22.5 % | −0.2 % | −22.5 % |
| Participants achieving ≥10 % loss | 87 % | 18 % | +69 pp |
| Participants achieving ≥20 % loss | 47.8 % | 4.6 % | +43.2 pp |
| Pre-diabetics returned to normoglycemia | 73 % | 7.5 % | +65.5 pp |
The study did not observe a weight-loss plateau at 48 weeks, suggesting room for additional reductions with longer treatment.
How Does CT-388 Compare With Tirzepatide and Semaglutide?
To put CT-388’s numbers in context, it helps to look at benchmark Phase III data from currently approved incretin therapies.
| Drug (Trial) | Dose | Duration | Mean % Weight Loss | Study Type |
|---|---|---|---|---|
| CT-388 (CT388-103) | 24 mg | 48 wk | −22.5 % | Phase II |
| Tirzepatide (SURMOUNT-1)(nejm.org) | 15 mg | 72 wk | −20.9 % | Phase III |
| Semaglutide (STEP 1)(nejm.org) | 2.4 mg | 68 wk | −14.9 % | Phase III |
Even at an earlier development stage and shorter follow-up, CT-388 matches or surpasses tirzepatide’s headline weight-loss figure and clearly exceeds semaglutide’s. Direct comparisons require caution because of differing study designs, but CT-388’s signal is undeniably strong.
What Side Effects Should You Expect?
Gastrointestinal (GI) symptoms are class-wide effects for incretin drugs. In the Phase II CT-388 study, nausea, diarrhea, and vomiting were the most common adverse events, predominantly mild to moderate. Only 5.9 % of CT-388 participants discontinued due to side effects versus 1.3 % on placebo.(gene.com)
| Drug | Nausea | Diarrhea | Vomiting |
|---|---|---|---|
| CT-388 24 mg (48 wk)(gene.com) | 31 % | 22 % | 12 % |
| Tirzepatide 15 mg (SURMOUNT-1)(nejm.org) | 31 % | 23 % | 12 % |
| Semaglutide 2.4 mg (STEP 1)(nejm.org) | 44 % | 30 % | 24 % |
The profile aligns closely with tirzepatide and appears slightly gentler than semaglutide, though confirmation awaits full peer-reviewed data. Like other GLP-1-based drugs, CT-388 will likely carry a boxed warning for thyroid C-cell tumors if approved, mirroring current Mounjaro(pi.lilly.com) and Wegovy labels.(dailymed.nlm.nih.gov)
Who Might Benefit Most From CT-388?
Based on early findings, CT-388 could be particularly useful if you:
- Need >20 % weight loss but have plateaued on single-agonist therapy.
- Prefer weekly injections over daily oral options.
- Have prediabetes and wish to normalize blood sugar alongside weight reduction.
- Require rapid titration to therapeutic doses (the CT-388 schedule achieves 24 mg in 12 weeks).
Not sure whether to wait for CT-388 or start an approved drug now?
| Consider This | If You Lean Toward CT-388 | If You Lean Toward Current Therapy |
|---|---|---|
| Urgency of weight loss | You can continue lifestyle changes while awaiting Phase III data. | You need proven, immediate treatment. |
| Insurance coverage | Willing to face potential out-of-pocket costs if early-access programs open. | Your plan already covers tirzepatide or semaglutide. |
| Risk tolerance | Comfortable with unknown long-term safety. | Prefer established safety database. |
When Could CT-388 Reach the Market?
Roche expects to launch two Phase III studies (Enith 1 and 2) by late 2026. Assuming typical 72-week primary endpoints, data could read out in 2028, allowing a 2029 FDA submission and potential approval in 2030. Delays are always possible, but CT-388’s fast-track designation may expedite review.(gene.com)
When to Contact Your Healthcare Provider
- Severe or persistent nausea, vomiting, or diarrhea leading to dehydration
- Signs of pancreatitis (severe abdominal pain radiating to the back)
- Lumps or swelling in the neck (possible thyroid issues)
- Vision changes or severe eye pain
- Hypoglycemia symptoms if you take other diabetes medications (shakiness, confusion, sweating)
- Allergic reactions such as rash, difficulty breathing, or swelling of face and throat
- Genentech. Genentech Announces Positive Phase II Results for Its Dual GLP-1/GIP Receptor Agonist CT-388 in People Living With Obesity. Press release, January 26 2026. Available at gene.com.(gene.com)
- ClinicalTrials.gov. NCT06525935: A Study of Enicepatide (CT-388) in Participants With Obesity or Overweight With at Least One Weight-Related Comorbidity. Updated 2026.(clinicaltrials.gov)
- Jastreboff AM, Aronne LJ, Ahmad NN, et al. Tirzepatide Once Weekly for the Treatment of Obesity. N Engl J Med. 2022;387:205-216. doi:10.1056/NEJMoa2206038.(nejm.org)
- Wilding JPH, Batterham RL, Davies M, et al. Once-Weekly Semaglutide in Adults with Overweight or Obesity. N Engl J Med. 2021;384:989-1002. doi:10.1056/NEJMoa2032183.(nejm.org)
- Eli Lilly and Co. Mounjaro (tirzepatide) Prescribing Information. Revised November 2024. pi.lilly.com.(pi.lilly.com)
- Novo Nordisk. Wegovy (semaglutide) Prescribing Information. Updated May 5 2026. DailyMed.(dailymed.nlm.nih.gov)
- Chakravarthy MV et al. Safety, Pharmacokinetics, and Pharmacodynamics of CT-388, a Signal-Biased Dual GLP-1/GIP Receptor Agonist, Over 24 Weeks in Adults With Obesity. Poster presented at EASD 2024. Genentech Medical Communications.(medically.gene.com)
Frequently Asked Questions
Is CT-388 the same as tirzepatide?
No. Both drugs target GLP-1 and GIP receptors, but CT-388 uses biased signaling designed to prolong receptor activation, whereas tirzepatide does not.
How much weight could I lose on CT-388?
In Phase II, people on the highest dose lost an average 22.5 % of body weight at 48 weeks, with nearly half losing ≥20 %. Individual results will vary.(gene.com)
Will CT-388 help my blood sugar?
Yes. Among participants with prediabetes, 73 % returned to normal glucose levels after 48 weeks on CT-388.(gene.com)
What are the most common side effects?
Mild to moderate nausea, diarrhea, and vomiting — similar to other GLP-1-based medications.
When will CT-388 be available?
Phase III trials start in late 2026. If successful, FDA approval could come as early as 2030.
Can I join a clinical trial?
You may search ClinicalTrials.gov for “CT-388” and discuss eligibility with your doctor.
Should I wait for CT-388 or start an approved GLP-1 now?
If you need treatment today, consider approved options like semaglutide or tirzepatide. Waiting may be reasonable if you and your provider prioritize maximal weight loss and are comfortable with trial participation.
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