Retatrutide vs VK2735: Triple Agonist vs Dual Agonist for Weight Loss

Introduction

In the next two years, obesity medicine will have more options than it's had in its entire history. Two of the most anticipated are retatrutide and VK2735 — both in Phase 3, both expected to reach patients by 2027–2028, and both targeting a very different patient than the current standard of care.

They share a foundation: both activate GLP-1 and GIP receptors. But retatrutide adds a third — glucagon. That single difference drives a dramatically different efficacy profile and a different side effect picture.

VK2735 comes with its own advantage: it exists in both subcutaneous and oral formulations, with Phase 3 trials running for both. If the oral form reaches approval, VK2735 could become the first oral dual GLP-1/GIP agonist on the market.

Neither drug is approved. Neither is available. But patients who are tracking what's coming need to understand what these two drugs actually do — and how they compare.

How Retatrutide and VK2735 Compare at a Glance

What VK2735 Is and How It Works

VK2735 is Viking Therapeutics' dual GLP-1/GIP receptor agonist — the same receptor combination as tirzepatide (Zepbound/Mounjaro), but a different molecule with a distinct pharmacology profile.

Mechanism:

• GLP-1: Appetite suppression, slows gastric emptying, stimulates insulin release
• GIP: Enhances GLP-1 effects, improves tolerability, may reduce nausea compared to GLP-1-only medications

The GLP-1 + GIP combination is what makes tirzepatide significantly more effective than semaglutide (GLP-1 only). VK2735 operates on the same principle.

Two formulations in development:

• Subcutaneous injection (weekly) — Phase 3 VANQUISH-1 (obesity) and VANQUISH-2 (obesity + type 2 diabetes)
• Oral tablet — Phase 2 VENTURE-Oral completed, Phase 3 registration studies planned

The oral formulation is what makes VK2735 strategically interesting beyond its efficacy. If approved, it would be the first oral GLP-1/GIP dual agonist — a category that doesn't currently exist.

What the Phase 2 Trial Data Shows

VK2735 Subcutaneous — VENTURE Trial (13 Weeks)

The Phase 2 VENTURE trial was short — only 13 weeks — but the results were striking. VK2735 achieved 14.7% weight loss at the highest subcutaneous dose in 13 weeks, with no plateau observed. This places it among the fastest-acting obesity drugs ever studied.

Key secondary endpoints:

• Nearly 97% of patients achieved ≥5% weight loss
• Approximately 80% achieved ≥10% weight loss
• Dose-dependent response across all cohorts
• Favorable tolerability — adverse events mostly mild to moderate GI effects

VK2735 Oral — VENTURE-Oral Trial (13 Weeks)

Presented at the European Congress on Obesity in May 2026, the oral formulation achieved 12.2% weight loss (approximately 26.6 lbs) at the highest dose over 13 weeks. Progressive weight loss was observed from Week 1 through Week 13 without plateau.

The oral Phase 2 enrolled 280 adults with BMI ≥30 kg/m². Over half had pre-diabetes — a population similar to the broader obesity treatment target.

Why 13-Week Data Requires Caution

VK2735's Phase 2 data covers only 13 weeks. Retatrutide's pivotal data runs 80 weeks. These are not comparable on a per-week basis — early weight loss rates are typically higher than long-term rates as body composition adapts.

What we don't yet know about VK2735:

• Does the 14.7% trajectory continue at the same pace beyond week 13?
• Does weight loss plateau at 20–22% (like tirzepatide), or does it continue?
• What are the VANQUISH-1 and VANQUISH-2 results at 52 and 78 weeks?

VANQUISH-1 (general obesity) results are expected in 2026–2027. Until then, long-term projections for VK2735 are extrapolations, not data.

Retatrutide's Phase 3 Results vs VK2735's Phase 2 Trajectory

Retatrutide — TRIUMPH Trials

TRIUMPH-4 (68 weeks, obesity + osteoarthritis, n=751): 28.7% average weight loss at 12mg.

TRIUMPH-1 (80 weeks, general obesity, n=2,339): 28.3% average weight loss at 12mg. Secondary endpoints: 45.3% of patients achieved ≥30% weight loss. 65.3% reached a BMI below 30. A prespecified 104-week extension showed continued loss reaching 30.3% — with no plateau at 80 weeks.

Note: VK2735 Phase 3 results are not yet available. VENTURE data covers only 13 weeks. Comparisons across trials should be interpreted with caution.

Why Retatrutide Produces More Weight Loss Than VK2735

The answer is the glucagon receptor.

Retatrutide is a triple agonist. VK2735 is a dual agonist — the same receptor combination as tirzepatide (GLP-1 + GIP). The ceiling for GLP-1/GIP dual agonists, based on tirzepatide's pivotal data, is approximately 22–25% average weight loss at 72 weeks.

Retatrutide's glucagon activation adds a third mechanism:

• Increases basal metabolic rate
• Enhances hepatic fat burning
• Drives energy expenditure independent of calorie restriction

This is why retatrutide's 28.3% average weight loss significantly exceeds what tirzepatide achieves — and why VK2735, if it follows a similar trajectory to tirzepatide, is unlikely to match retatrutide's efficacy even in long-term Phase 3 data.

VK2735's 14.7% at 13 weeks is impressive — faster than early tirzepatide data suggested. But if VANQUISH-1 results land at 22–24% at 52+ weeks, that would represent a meaningful gap compared to retatrutide at 28–30%.

For a detailed explanation of how retatrutide's triple mechanism drives its efficacy, see our complete retatrutide guide.

The Case for VK2735: Why It Matters Despite Lower Efficacy

VK2735 doesn't need to beat retatrutide to be important. It needs to be better than what's currently available — and based on Phase 2 data, it likely is.

Why VK2735 may be the right choice for many patients:

An oral option is coming. If the VK2735 oral Phase 3 succeeds, it would offer dual GLP-1/GIP agonism in pill form — something that doesn't currently exist. Foundayo (orforglipron) is a GLP-1-only pill. VK2735 oral would add GIP activation, which may translate to meaningfully higher weight loss than Foundayo's 11.2%.

Potentially better tolerability. VK2735's Phase 2 data showed favorable GI tolerability. No dysesthesia (the abnormal skin sensations seen in 20.9% of retatrutide patients at 12mg). If VANQUISH confirms this profile, VK2735 may have a significantly better side effect burden than retatrutide.

Competition drives access. Multiple effective obesity medications entering the market simultaneously creates pricing pressure. The more drugs compete, the more likely patients are to gain access through insurance. VK2735's commercial success matters even for patients who want retatrutide.

Adequate for many patients. A patient at BMI 32 with no severe comorbidities may achieve their health goals at 20–22% weight loss. For them, VK2735's projected efficacy is sufficient — and the oral option, if tolerable, removes the injection barrier entirely.

For detailed information on retatrutide's unique side effect profile, see our retatrutide side effects guide.

VK2735 Phase 3 Program: What VANQUISH Will Show

The VANQUISH Phase 3 program consists of two subcutaneous trials:

VANQUISH-1: General obesity (BMI ≥30 or ≥27 with comorbidities), no diabetes. Enrollment completed November 2025. Results expected 2026–2027. Duration: 52 weeks.

VANQUISH-2: Obesity with type 2 diabetes (BMI ≥30 or ≥27 overweight). Enrollment completed March 2026. Duration: 78 weeks.

Oral Phase 3 registration studies are planned but not yet initiated as of June 2026.

What to watch for in VANQUISH-1:

• Does weight loss plateau below 20%, or does it reach tirzepatide-level 22–25%?
• Discontinuation rates — will they be lower than retatrutide's 11.3–18.2%?
• Cardiovascular risk factor improvements (blood pressure, lipids, HbA1c)
• Any unexpected side effects at longer treatment durations

If VANQUISH-1 results confirm 20%+ weight loss with favorable tolerability, VK2735 becomes one of the most compelling obesity drugs in the pipeline — not because it beats retatrutide, but because it offers a meaningful step up from tirzepatide with potentially better tolerability.

Retatrutide vs VK2735: Who Should Wait for Which?

Both drugs are in development. Neither is available. The question is which pipeline drug better fits a given patient's needs.

Retatrutide is likely the better choice for patients who:

• Have severe obesity (BMI ≥40) and need maximum weight loss
• Have multiple metabolic complications (fatty liver, insulin resistance, osteoarthritis)
• Have already tried tirzepatide or a GLP-1/GIP dual agonist without adequate response — retatrutide's glucagon component offers a genuinely different mechanism
• Don't mind weekly injections and want the highest available efficacy

VK2735 may be the better choice for patients who:

• Are waiting for an oral option — the oral Phase 3 could deliver GLP-1/GIP dual agonism without injection
• Have had tolerability issues with current injectables — early data suggests a favorable GI profile
• Need 18–22% weight loss rather than 28%+ — adequate for moderate obesity
• Want a drug from a large pharma-backed pipeline (Viking's partnership discussions could shape commercial access)

The most likely scenario: both drugs reach the market. Physicians prescribe based on individual patient profiles — retatrutide for maximum efficacy cases, VK2735 (especially oral) for patients prioritizing convenience and tolerability.

What Retatrutide and VK2735 Mean for the Future of Obesity Treatment

The arrival of two new obesity medications simultaneously — one with triple agonism, one with an oral form — represents a shift in what's possible.

The current standard, tirzepatide, achieves 22.5% average weight loss at 72 weeks. Retatrutide adds ~6 percentage points beyond that with glucagon activation. VK2735 may land near tirzepatide's range — but in a pill.

For the roughly 100 million Americans with obesity, the bottleneck has never been efficacy alone. It's been access, cost, format, and tolerability. Retatrutide addresses efficacy ceiling. VK2735 oral addresses format. Together, they represent the expansion of obesity medicine to patients it couldn't previously reach.

Conclusion

Retatrutide and VK2735 are not competing for the same patient. They represent different solutions to different problems.

Retatrutide is the efficacy answer — 28.3% average weight loss at 80 weeks, confirmed in 2,339 patients, with no plateau. If your obesity requires maximum pharmacological intervention, nothing in the current pipeline matches it.

VK2735 is the access answer — a drug that may deliver meaningful weight loss in both injectable and oral forms, with a potentially gentler side effect profile than anything currently available. It won't produce bariatric surgery-level results, but it may bring GLP-1/GIP dual agonism to patients who can't or won't inject.

VANQUISH-1 results, expected in 2026–2027, will determine whether VK2735's Phase 2 promise translates to Phase 3 confirmation. Until then, retatrutide holds the strongest clinical evidence of any drug in this class.

For the latest on retatrutide's timeline and what comes next before FDA approval, see our TRIUMPH-1 results page.

Sources

• Jastreboff AM, et al. TRIUMPH-1 Phase 3 topline results, including 80-week and 104-week extension data. Eli Lilly. May 21, 2026.
• Eli Lilly TRIUMPH-4 Phase 3 topline results. December 2025.
• Viking Therapeutics. Phase 2 VENTURE trial results — subcutaneous VK2735. Published in Obesity, January 2026.
• Viking Therapeutics. Phase 2 VENTURE-Oral Dosing trial data presented at ECO 2026. May 12, 2026.
• Viking Therapeutics. VANQUISH-2 enrollment completion announcement. March 26, 2026.