What Is Enicepatide (RO7795068)? The Dual GLP-1/GIP Agonist Moving Into Phase 3

Enicepatide is one of Roche’s most important emerging metabolic drug candidates.

Previously known as CT-388 and also identified as RO7795068, enicepatide is an investigational once-weekly dual GLP-1/GIP receptor agonist being developed for obesity, overweight and type 2 diabetes. (genentech-medinfo⁠)

What makes it particularly interesting is that the programme has now moved beyond early proof-of-concept research.

In September 2026, Roche reported positive Phase 2 results in people with type 2 diabetes and overweight or obesity, while Phase 3 obesity trials are already recruiting. (Roche⁠)

What Is Enicepatide?

Enicepatide is an investigational peptide-based medicine designed to activate two incretin receptors:

• GLP-1
• GIP

It is administered by once-weekly subcutaneous injection.

The compound was originally developed as CT-388 and is now being developed by Roche under the name enicepatide. (genentech-medinfo⁠)

What Do GLP-1 and GIP Do?

GLP-1 and GIP are naturally occurring hormones released after eating.

GLP-1 contributes to:

• appetite regulation
• satiety
• insulin release
• blood-glucose control
• slowing of gastric emptying

GIP also contributes to insulin signalling and nutrient handling.

Combining the two pathways in a single molecule is intended to produce complementary metabolic effects.

How Is Enicepatide Different From a Standard GLP-1 Agonist?

A conventional GLP-1 receptor agonist primarily activates one receptor.

Enicepatide activates both:

GLP-1 + GIP

That makes it part of the same broad class of dual incretin research as tirzepatide and several other next-generation obesity drugs.

But enicepatide has its own molecular design and receptor-signalling profile.

What Does “Biased Agonist” Mean?

Enicepatide is described by Roche as a biased dual GLP-1/GIP receptor agonist.

That means it does not necessarily activate every signalling pathway downstream of those receptors equally.

Roche reports that enicepatide is biased toward cAMP signalling, with minimal or no recruitment of a signalling protein called β-arrestin at either receptor. (genentech-medinfo⁠)

Researchers are interested in biased agonism because different intracellular signalling pathways can influence:

• effectiveness
• receptor desensitisation
• duration of action
• tolerability

Whether this produces a meaningful clinical advantage will ultimately need to be demonstrated in direct human comparisons.

What Did the Phase 2 Diabetes Trial Show?

In September 2026, Roche announced results from the Phase 2 CT-388-104 study.

The trial enrolled adults with type 2 diabetes and overweight or obesity.

At the highest tested dose of 24 mg, Roche reported an average HbA1c reduction of 2.65 percentage points at 48 weeks. (Roche⁠)

Participants began with an average HbA1c of around 8.1%.

That represents a substantial change in glycaemic control.

What Happened in People With Poorer Baseline Glucose Control?

The results were even more striking in participants who began with HbA1c above 8.5%.

Roche reported an average HbA1c reduction of approximately 4.13 percentage points at the 24 mg dose. (Roche⁠)

This suggests enicepatide may have particularly strong glucose-lowering effects in people starting with more severe dysglycaemia.

That finding will need confirmation in larger Phase 3 trials.

How Many Participants Reached Normal Glucose Levels?

At 48 weeks, Roche reported that:

• 90% of participants receiving 24 mg reached HbA1c of 6.5% or below
• 62% reached HbA1c below 5.7%

The latter falls within the laboratory range generally used to define normoglycaemia. (Roche⁠)

These are impressive Phase 2 findings, although they come from a company-reported trial and still need confirmation in a larger late-stage programme.

What About Weight Loss?

Weight reduction was also substantial.

At the 24 mg dose, participants experienced average weight loss of approximately 15.5% at 48 weeks. (Roche⁠)

Importantly, Roche reported that the weight-loss curve had not reached a clear plateau by week 48.

That suggests additional weight reduction may potentially occur with longer treatment, although this cannot be assumed until longer studies are completed.

Why Is the Lack of a Plateau Interesting?

Many metabolic drugs produce rapid early weight loss followed by a gradual slowing.

If a treatment continues producing weight reduction without reaching a plateau during the studied period, researchers naturally want to know what happens with longer exposure.

But this does not mean weight will continue declining indefinitely.

Biological adaptation eventually limits weight reduction with most therapies.

Longer Phase 3 trials will provide a clearer picture.

What Were the Side Effects?

Roche reported that the most common adverse effects were gastrointestinal, consistent with the broader incretin class.

These effects were mostly mild to moderate.

Treatment discontinuation due to adverse events was reported in approximately 2% of participants receiving enicepatide, compared with none in the placebo group. (Roche⁠)

No new major safety signal was identified in the Phase 2 programme.

However, Phase 2 studies are not large enough to identify every potential uncommon or long-term adverse effect.

Has Enicepatide Reached Phase 3?

Yes.

Two major Phase 3 obesity studies are already recruiting.

These are:

ENITH-1 — obesity or overweight without type 2 diabetes.

ENITH-2 — obesity or overweight with type 2 diabetes.

Genentech currently lists both studies as recruiting Phase 3 trials. (genentech-medinfo⁠)

What Is ENITH-1?

ENITH-1 is studying once-weekly enicepatide in adults with obesity or overweight who do not have type 2 diabetes.

The trial is comparing several doses of enicepatide with placebo.

Its purpose is to evaluate both:

• weight-management effectiveness
• safety

Roche lists the study under ClinicalTrials.gov identifier NCT07351045. (forpatients.roche.com⁠)

What About Type 2 Diabetes?

ENITH-2 is studying enicepatide in adults with obesity or overweight who also have type 2 diabetes.

This population is particularly important because both:

• weight reduction
• glycaemic control

need to be evaluated together.

The earlier Phase 2 findings suggest that glucose control may be one of enicepatide’s strongest potential differentiators.

Is Enicepatide Being Combined With Petrelintide?

Yes.

This is one of the most interesting parts of Roche’s obesity programme.

Roche announced plans for a Phase 2 multi-arm study evaluating fixed-dose combinations of enicepatide and petrelintide. (Roche⁠)

The combination would bring together:

GLP-1/GIP signalling from enicepatide

with

amylin signalling from petrelintide

That effectively creates a three-pathway metabolic strategy without requiring all three receptor activities to be engineered into a single peptide.

Why Combine Incretin and Amylin Pathways?

GLP-1 and GIP influence appetite, glucose control and nutrient handling.

Amylin also influences satiety and food intake but operates through a different hormonal pathway.

Combining these systems could potentially provide:

• greater weight reduction
• different appetite effects
• improved tolerability
• better long-term adherence

The combination remains experimental, and direct evidence is still being generated.

How Is Enicepatide Different From Tirzepatide?

Both activate:

GIP + GLP-1

But they are different molecules with different receptor-signalling characteristics.

Enicepatide’s biased signalling profile is one feature Roche hopes could differentiate it.

Tirzepatide already has extensive clinical data and regulatory approval.

Enicepatide remains investigational.

Direct comparative trials would be needed before claiming that one is better than the other.

How Is Enicepatide Different From VK2735?

Again, both activate GIP and GLP-1.

VK2735 is being developed in both injectable and oral formats.

Enicepatide is currently focused on a once-weekly injectable programme and combination strategies with petrelintide.

The real differences will emerge from:

• efficacy
• tolerability
• dose requirements
• body-composition effects
• glucose control
• long-term safety

How Is Enicepatide Different From Ribupatide?

Ribupatide also targets GIP and GLP-1.

The three compounds therefore occupy a very competitive research space.

Each developer is attempting to optimise slightly different properties such as:

• receptor balance
• signalling bias
• pharmacokinetics
• tolerability
• formulation
• combination potential

This competition is likely to produce increasingly sophisticated incretin drugs.

Is Enicepatide a Peptide?

Yes.

Enicepatide is a peptide-based dual incretin receptor agonist.

It therefore fits naturally within research into next-generation metabolic peptides.

Is Enicepatide Approved?

No.

Enicepatide remains an investigational drug.

It has progressed into Phase 3 trials, but it has not yet been approved for routine clinical use.

The current Phase 3 programme will need to establish its:

• long-term effectiveness
• safety
• optimal dose
• effects across different populations
• cardiovascular profile
• comparative value against established therapies

Why Is Enicepatide Worth Watching?

The obesity pipeline already contains several dual GIP/GLP-1 agonists.

So simply targeting those two receptors is no longer enough to make a molecule particularly unusual.

What makes enicepatide interesting is the combination of:

• biased receptor signalling
• substantial Phase 2 glucose reduction
• meaningful weight reduction
• low reported discontinuation rates
• Phase 3 progression
• planned combination with an amylin analogue

That gives the programme several different potential development paths.

The Bottom Line

Enicepatide, previously known as CT-388 and RO7795068, is an investigational once-weekly dual GLP-1/GIP receptor agonist now in Phase 3 development. (genentech-medinfo⁠)

In a 48-week Phase 2 trial involving adults with type 2 diabetes and overweight or obesity, Roche reported:

• average HbA1c reduction of 2.65 percentage points
• average weight reduction of 15.5%
• 90% of participants at the highest dose reaching an HbA1c of 6.5% or below
• 62% reaching normoglycaemic HbA1c levels

all at the 24 mg dose. (Roche⁠)

The compound has now entered the Phase 3 ENITH programme, while Roche is also exploring combinations of enicepatide with the amylin analogue petrelintide. (genentech-medinfo⁠)

Those developments make enicepatide one of the more important emerging metabolic peptides to watch.

This article is for research and educational purposes only. Enicepatide remains investigational and is not presented as an approved or established treatment.