Enicepatide (CT-388, RO7795068) is Roche’s investigational once-weekly GLP-1 and GIP dual agonist, designed to signal in a “biased” way that keeps its receptors on the cell surface. In a 48-week phase 2 trial, the 24 mg dose produced 22.7% average weight loss vs 0.2% on placebo, with no plateau. Phase 3 trials started in March 2026, and it is not approved anywhere.
The single most important fact: enicepatide is an experimental drug available only in Roche’s trials. As of November 7, 2026, two pivotal obesity trials (ENITH-1 and ENITH-2) are recruiting, with estimated primary completion in July and August 2028. Roche has also registered a head-to-head diabetes trial against tirzepatide and a cardiovascular outcomes trial. No body-composition data have been released. Roche itself lists muscle preservation as an unmet need in obesity care.
This page summarizes what the published studies, company presentations and trial registrations report. It is for education only and is not medical advice.
| Property | Detail |
|---|---|
| Drug class | Dual GLP-1 and GIP receptor agonist; cAMP signal-biased peptide |
| Codes | CT-388 (Carmot Therapeutics); RO7795068 and RG6640 (Roche) |
| Developer | Roche, via its acquisition of Carmot Therapeutics (announced December 4, 2023) |
| Route | Subcutaneous injection once weekly |
| Doses studied | 0.5–7.5 mg single doses and 5–12 mg weekly (phase 1); 4–24 mg weekly (phase 2) |
| Half-life | Supports once-weekly dosing; a numeric human value is not given in the sources we could access |
| Status (November 7, 2026) | Phase 3 (ENITH program); not approved; no regulatory filing |
| WADA status | Not named on the 2026 List; unapproved, so it falls under S0 (non-approved substances) |
What it is
Enicepatide is a single peptide that activates two incretin receptors, GLP-1 and GIP. That is the same pair targeted by tirzepatide, ribupatide and VK2735. It was the lead asset of Carmot Therapeutics, a California biotech. Roche agreed to buy Carmot for $2.7 billion in cash plus up to $400 million in milestones. The deal also included the oral GLP-1 drug CT-996 and the injectable CT-868 (Roche, December 2023).
Signal bias
When a hormone activates a receptor, the receptor can send signals through several routes inside the cell. Two matter here:
- cAMP signaling drives the insulin and appetite effects.
- Beta-arrestin recruitment helps pull the receptor inside the cell (internalization), which can dampen the response over time.
Enicepatide was designed to trigger cAMP signaling at both receptors with minimal beta-arrestin recruitment. In cell tests, it activated the GLP-1 and GIP receptors with minimal receptor internalization compared with the natural hormones (Chakravarthy et al., Mol Metab 2026). The hypothesis is that receptors left on the cell surface keep responding, which would sustain weight loss. That is a laboratory rationale. No trial has shown that enicepatide outperforms an unbiased drug like tirzepatide.
How it compares with related drugs
| Drug | Receptors | Status (November 2026) | Library page |
|---|---|---|---|
| Tirzepatide | GIP and GLP-1 | Approved | Tirzepatide |
| Enicepatide | GIP and GLP-1, signal-biased | Phase 3 | This page |
| Ribupatide | GIP and GLP-1 | Under review in China | Ribupatide |
| VK2735 | GIP and GLP-1 | Phase 3 | VK2735 |
| Petrelintide | Amylin (partner molecule in Roche’s combination trials) | Phase 2–3 | Petrelintide |
| Semaglutide | GLP-1 | Approved | Semaglutide |
Pharmacokinetics
The phase 1 study (NCT04838405) gave single doses of 0.5–7.5 mg or four weekly doses of 5–12 mg to otherwise healthy adults with overweight or obesity. The authors reported that pharmacokinetics supported once-weekly dosing and were consistent across mice, monkeys and humans. Mean weight change at day 29 was −4.7% to −8.0% across doses vs −0.5% on placebo, and glucose control improved during fasting and a glucose tolerance test (Chakravarthy et al., Mol Metab 2026). A numeric half-life is not stated in the abstract.
Regulatory status
Status checked on November 7, 2026 using ClinicalTrials.gov and Roche releases:
- Not approved, not filed. No regulator has received an application. Roche’s July 2026 half-year presentation lists enicepatide among new molecules heading toward regulatory submission (Roche HY 2026 presentation). Results from the pivotal trials are not due until 2028.
- Phase 3 and late-stage trials:
| Trial | NCT number | Design | Planned size | Status and key dates |
|---|---|---|---|---|
| ENITH-1 | NCT07351045 | Obesity or overweight without type 2 diabetes vs placebo | 2,000 | Recruiting; started March 16, 2026; primary completion est. July 24, 2028 |
| ENITH-2 | NCT07351058 | Obesity or overweight with type 2 diabetes vs placebo | 1,600 | Recruiting; started March 23, 2026; est. August 7, 2028 |
| China phase 3 | NCT07670416 | Chinese adults, with or without type 2 diabetes | 300 | Recruiting; started July 3, 2026; est. February 24, 2028 |
| ENI-SPIRE-2 | NCT07889648 | Open-label, vs tirzepatide, type 2 diabetes on oral drugs; HbA1c at week 72 | 948 | Not yet recruiting; planned start December 2026 |
| Enith-MACE | NCT07918846 | Cardiovascular outcomes (5-point MACE) in overweight or obesity with heart disease | 8,200 | Not yet recruiting; planned start January 2027 |
| ZYNERGY (phase 2) | NCT07589686 | Dose-finding with the amylin analogue petrelintide | 486 | Not yet recruiting; planned start November 30, 2026 |
ENI-SPIRE-2 is the first registered head-to-head trial against tirzepatide. Because it measures blood sugar in diabetes rather than weight loss in obesity, it will not settle which drug causes more weight loss.
What the research shows
Obesity without diabetes (CT388-103, phase 2)
This 48-week, double-blind trial (NCT06525935) randomized 469 adults with obesity, or overweight with at least one weight-related condition, and no type 2 diabetes. Participants were assigned to placebo or one of five dose-escalation cohorts up to 24 mg weekly (Roche, January 2026). Full results were presented at the American Diabetes Association meeting in June 2026 (Roche ADA 2026 investor presentation):
| Target dose | Weight change at 48 weeks (efficacy estimand) | Placebo-adjusted difference (treatment-regimen estimand) |
|---|---|---|
| Placebo | −0.2% | — |
| 4 mg | −6.7% | −5.0 points |
| 8 mg | −14.2% | −10.7 points |
| 12 mg | −16.6% | −11.7 points |
| 16 mg | −18.4% | −13.4 points |
| 24 mg | −22.7% | −18.3 points |
The efficacy estimand assumes participants stayed on treatment; the treatment-regimen estimand counts everyone regardless. At 24 mg the placebo-adjusted difference was 22.5 points under the efficacy estimand. Among people on 24 mg:
- 95.7% lost at least 5% of body weight, 87% at least 10%, 47.8% at least 20% and 26.1% at least 30%;
- 54% ended below a BMI of 30, vs 13% on placebo;
- 73% of those with prediabetes reached normal blood sugar, vs 7.5% on placebo.
Weight was still falling at week 48, which is why the phase 3 trials run longer.
Obesity with type 2 diabetes (CT-388-104, phase 2)
This trial (NCT06628362) enrolled 447 adults with type 2 diabetes and overweight or obesity. At 48 weeks on 24 mg, HbA1c fell by 2.65 points from a baseline of 8.1%. In people starting above 8.5%, it fell by 4.13 points. Ninety percent reached an HbA1c of 6.5% or lower, and 62% reached below 5.7%. Mean weight loss was 15.5%, again without a clear plateau (Roche, September 2026). These are changes from baseline in a topline release. Placebo-adjusted values have not been published.
Body composition: no data yet
Enicepatide is not an anabolic drug, and no DXA or MRI body-composition data have been released. Roche’s January 2026 phase 2 release did not mention lean mass. A search of all enicepatide and CT-388 records on ClinicalTrials.gov on November 7, 2026 found no listed outcome for lean mass, fat-free mass, DXA or muscle.
Roche treats muscle loss as a gap in current treatment. Its June 2026 investor presentation listed “muscle mass preservation” among unmet needs and stated that “up to 40% of weight loss comes from muscle loss” (Roche ADA 2026 presentation). Independent reviews put the average lean share lower: 29.1% across 40 DXA reports of GLP-1-based drugs (Dubin et al., Obesity 2026) and 33.3% in a meta-analysis of incretin trials with at least 10% weight loss (Busk-Cirera et al., Diabetes Obes Metab 2026).
Roche’s main muscle-sparing strategy is a separate drug. Emugrobart (RG6237, GYM329) is an antibody against latent myostatin, a protein that limits muscle growth. In the GYMINDA phase 2 trial (NCT06965413), it is tested in combination with tirzepatide, not enicepatide. For athletes, note that myostatin inhibitors, including myostatin-neutralizing antibodies, are prohibited at all times under S4.3 of the WADA 2026 Prohibited List. Related compounds on this site include bimagrumab and apitegromab.
Use alongside testosterone or anabolic steroids
No trial has combined enicepatide with TRT or anabolic steroids. A 2026 review of GLP-1 drugs and testosterone found no randomized trials of the combination on body composition (Canal de Velasco et al., Cureus 2026). Extrapolating from approved drugs to an investigational one adds a further layer of uncertainty.
Side effects and risks
Gastrointestinal effects
Gastrointestinal side effects rose with dose in the obesity phase 2 trial (Roche ADA 2026 presentation):
| Adverse event | Placebo (n=79) | 4 mg | 8 mg | 12 mg | 16 mg | 24 mg (n=76) |
|---|---|---|---|---|---|---|
| Any gastrointestinal disorder | 28% | 49% | 47% | 52% | 58% | 65% |
| Nausea | 19% | 33% | 36% | 39% | 41% | 46% |
| Constipation | 8% | 26% | 23% | 22% | 24% | 24% |
| Diarrhea | 10% | 14% | 14% | 16% | 18% | 32% |
| Vomiting | 0% | 8% | 12% | 25% | 23% | 21% |
| Any serious adverse event | 0% | 4% | 3% | 3% | 1% | 5% |
Most gastrointestinal events were mild to moderate, and no deaths occurred. Pooled across active arms, 5.9% stopped treatment because of adverse events vs 1.3% on placebo (Roche, January 2026). In the diabetes trial, 2.0% stopped for adverse events vs 0.0% on placebo (Roche, September 2026).
Gaps in the safety data
- Small trials. Fewer than 1,000 people have completed phase 2. Rare events such as pancreatitis or gallbladder disease cannot be judged.
- Topline data. The phase 2 results are company-reported and not yet in a peer-reviewed journal.
- Class warnings. Approved GLP-1-based drugs such as semaglutide carry warnings for thyroid C-cell tumors in rodents, pancreatitis, gallbladder disease and heart rate increase (Wegovy label, DailyMed). Whether these apply to enicepatide is not yet known.
Unregulated products
Enicepatide is available only inside Roche’s trials. Products sold online as “CT-388” or “enicepatide” are not Roche’s drug, and their identity, purity, dose and sterility cannot be assumed.
Legal status and use in sport
Enicepatide is not named on the WADA Prohibited List, and GLP-1 drugs as a class are not prohibited. However, S0 bans “any pharmacological substance” with “no current approval by any governmental regulatory health authority for human therapeutic use,” including “drugs under pre-clinical or clinical development” (WADA 2026 Prohibited List). As an investigational drug, enicepatide falls under S0 and is prohibited at all times.
WADA’s 2026 Monitoring Program tracks markers of semaglutide and tirzepatide, the approved drugs in this class (WADA 2026 Monitoring Program). Anti-doping reviews conclude that current evidence does not show incretin drugs improve physical performance in humans, while noting that these drugs reduce lean mass along with fat (La Vignera and Condorelli, Int J Mol Sci 2026).
Key takeaways
- A biased GLP-1/GIP agonist. Enicepatide targets the same receptors as tirzepatide but was designed to activate cAMP signaling with minimal receptor internalization.
- Large phase 2 weight loss. The 24 mg dose gave −22.7% at 48 weeks vs −0.2% on placebo; 26.1% of people lost at least 30%.
- Phase 3 since March 2026. ENITH-1 and ENITH-2 report around mid-2028; a diabetes trial against tirzepatide and an 8,200-person cardiovascular trial are planned to start by early 2027.
- Nausea is common at the top dose. At 24 mg, 46% reported nausea and 21% vomiting; 5.9% stopped for adverse events across active arms.
- No lean-mass data. No body-composition results or registered lean-mass outcomes exist; Roche is testing a myostatin antibody (WADA-prohibited) with tirzepatide, not with enicepatide.
- Banned in tested sport for now. As an unapproved drug it falls under WADA S0.
Sources
- Roche. Roche to acquire Carmot Therapeutics. Press release, December 4, 2023. Roche.
- Chakravarthy MV, Rodriguez R, Hergarden A, et al. 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. Mol Metab. 2026;103:102291. PubMed.
- Roche. Phase II results for CT-388 in people with obesity or overweight. Press release, January 27, 2026. Roche.
- Roche. ADA 2026 investor event presentation. June 8, 2026. Roche.
- Roche. Positive phase II results for enicepatide in people living with type 2 diabetes and overweight or obesity. Press release, September 22, 2026. Roche.
- Roche. HY 2026 results presentation. July 23, 2026. Roche.
- ClinicalTrials.gov. ENITH-1: a clinical study to evaluate the effects of enicepatide (RO7795068) in participants with obesity or overweight. NCT07351045. ClinicalTrials.gov.
- ClinicalTrials.gov. ENITH-2: a clinical study to evaluate the effects of enicepatide (RO7795068) in participants with obesity or overweight and type 2 diabetes. NCT07351058. ClinicalTrials.gov.
- ClinicalTrials.gov. ENI-SPIRE-2: enicepatide versus tirzepatide in type 2 diabetes. NCT07889648. ClinicalTrials.gov.
- ClinicalTrials.gov. Enith-MACE: enicepatide in participants with overweight or obesity and cardiovascular disease. NCT07918846. ClinicalTrials.gov.
- ClinicalTrials.gov. Other enicepatide trials: phase 2 CT388-103, NCT06525935; phase 2 CT-388-104, NCT06628362; phase 3 in Chinese adults, NCT07670416; ZYNERGY, NCT07589686. ClinicalTrials.gov.
- ClinicalTrials.gov. GYMINDA: RO7204239 (emugrobart) in combination with tirzepatide. NCT06965413. ClinicalTrials.gov.
- Dubin RL, Sanders TN, Schwab HM, et al. Glucagon-Like Peptide-1 Receptor Agonist-Based Agents and Body Composition: Filling More Gaps. Obesity (Silver Spring). 2026;34(Suppl 2):51–63. PubMed.
- Busk-Cirera L, Carlsen IØ, Madsen LB, et al. Effects of Incretin-Based Therapies, Diet and Exercise Interventions, and Bariatric Surgery on Fat-Free Mass in Adults With Overweight or Obesity: A Systematic Review and Meta-Analysis. Diabetes Obes Metab. 2026;28(9):7737–7751. PubMed.
- Canal de Velasco LM, González Flores JE, Kraus Fischer G, et al. Testosterone Replacement Therapy as a Potential Strategy to Preserve Lean Mass in Men With Persistently Low Serum Testosterone Receiving GLP-1 Receptor Agonists: A Narrative Review. Cureus. 2026;18(3):e105734. PubMed.
- La Vignera S, Condorelli RA. Incretin-Based Therapies in Sports: Pharmacological Mechanisms, Performance-Enhancing Potential, and Anti-Doping Implications—A Narrative Review. Int J Mol Sci. 2026;27(14):6116. PubMed.
- Novo Nordisk. Wegovy (semaglutide) injection prescribing information. Revised June 2026. DailyMed.
- World Anti-Doping Agency. The 2026 Prohibited List. WADA 2026 Prohibited List.
- World Anti-Doping Agency. The 2026 Monitoring Program. WADA.