Is survodutide better than tirzepatide for weight loss?

It is too early to answer definitively. Survodutide's Phase 2 data showed up to 18.7% weight loss at 46 weeks, which is impressive but cannot be directly compared to tirzepatide's Phase 3 SURMOUNT data showing 20.9% at 72 weeks. Phase 3 survodutide results (expected 2026-2027) will provide a fair comparison. For now, tirzepatide has the stronger evidence base.

What makes survodutide different from tirzepatide?

The key difference is the second receptor target. Tirzepatide targets GLP-1 + GIP receptors, while survodutide targets GLP-1 + glucagon receptors. Glucagon agonism promotes direct fat burning, thermogenesis, and hepatic fat oxidation. GIP co-agonism enhances appetite suppression through different central nervous system pathways. Both strategies enhance the GLP-1 backbone but through different metabolic mechanisms.

When will survodutide be available?

Survodutide is currently in Phase 3 clinical trials (ACHIEVE program for obesity, SYMPHONY for MASH). The earliest possible FDA approval is estimated at 2027-2028, assuming positive Phase 3 results and a standard regulatory timeline. It is currently only available through enrollment in clinical trials.

Is survodutide better for fatty liver disease?

Survodutide has a strong mechanistic rationale for MASH treatment because the glucagon receptor is heavily expressed in the liver and glucagon signaling directly promotes hepatic fat oxidation. Phase 2 MASH data showed 47-64% MASH resolution rates. However, tirzepatide is also being studied for MASH. Until both have Phase 3 liver data, a definitive comparison is premature.

Does survodutide raise blood sugar since it has glucagon activity?

Glucagon does raise blood glucose, but survodutide's GLP-1 component counterbalances this effect. In Phase 2 trials, glycemic control was maintained or improved in participants, including those with type 2 diabetes. The dual mechanism is specifically designed so that the GLP-1 agonism offsets the hyperglycemic tendency of glucagon receptor activation.

Survodutide vs Tirzepatide: The Next-Gen GLP-1 Comparison

The Dual Agonist Landscape: Two Strategies, Different Targets

The GLP-1 weight loss space is evolving beyond single-receptor agonists like semaglutide. The next frontier involves dual and triple agonists that target multiple metabolic receptors simultaneously. Two compounds define this emerging competition: tirzepatide (Mounjaro/Zepbound) and survodutide (BI 456906).

Both are dual agonists, but they target different receptor combinations — and this distinction matters enormously for their clinical profiles, side effects, and potential applications.

Tirzepatide is a GLP-1/GIP dual agonist. It stimulates both the GLP-1 receptor and the glucose-dependent insulinotropic polypeptide (GIP) receptor.
Survodutide is a GLP-1/glucagon dual agonist. It stimulates the GLP-1 receptor and the glucagon receptor.

These are fundamentally different therapeutic strategies. Understanding why requires a brief look at what each co-targeted receptor does.

Mechanisms Compared: GIP vs Glucagon Co-Agonism

Tirzepatide's GIP Component. GIP was historically considered an "obesity-promoting" hormone because it enhances nutrient storage. The discovery that pharmacological GIP receptor agonism combined with GLP-1 agonism actually enhances weight loss was initially counterintuitive. The current understanding is that high-dose GIP agonism may produce a form of receptor desensitization that functionally antagonizes GIP signaling, while the direct central nervous system effects of GIP receptor activation in the brain contribute to appetite suppression. Tirzepatide's SURMOUNT trials showed approximately 20-22% weight loss at the highest dose — surpassing anything semaglutide achieved alone.

Survodutide's Glucagon Component. Glucagon is the counter-regulatory hormone to insulin: it raises blood glucose, stimulates lipolysis (fat breakdown), and increases energy expenditure. Activating the glucagon receptor directly promotes fat burning and thermogenesis. The challenge is that glucagon also raises blood sugar, which is problematic in a metabolic disease context. The solution: combine glucagon agonism with GLP-1 agonism, letting the GLP-1 component offset glucagon's hyperglycemic effect while preserving its metabolic benefits. This creates a compound that simultaneously suppresses appetite (GLP-1), burns fat (glucagon), and maintains glycemic control (GLP-1 counterbalancing glucagon).

For the broader context of how these compounds compare to single agonists, see our semaglutide vs tirzepatide comparison and our weight loss goals page.

Clinical Trial Data

Tirzepatide (SURMOUNT Program — Completed):

Trial	Dose	Duration	Weight Loss
SURMOUNT-1	5/10/15 mg weekly	72 weeks	-15.0% / -19.5% / -20.9%
SURMOUNT-2 (T2D)	10/15 mg weekly	72 weeks	-12.8% / -14.7%
SURMOUNT-3 (+ lifestyle)	10/15 mg weekly	72 weeks	-18.4% / -21.1% (from run-in)

Survodutide (Phase 2 Data):

Trial	Dose	Duration	Weight Loss
Phase 2 Obesity	0.6-4.8 mg weekly	46 weeks	Up to -18.7% (4.8 mg)
Phase 2 MASH	2.4-6.0 mg weekly	48 weeks	-13% to -16% (dose-dependent)

Interpreting the Numbers. Tirzepatide's SURMOUNT data is Phase 3 (large, well-powered trials). Survodutide's data is Phase 2 (smaller, dose-finding trials). Direct comparison of Phase 2 and Phase 3 numbers is inherently imprecise. That said, survodutide's 18.7% weight loss at 46 weeks is striking — if the trajectory continued to 72 weeks (the standard comparison duration), it could potentially match or approach tirzepatide's 20%+ results. Phase 3 data for survodutide is expected in 2026-2027.

The MASH Advantage: Where Survodutide May Win

One area where survodutide has a compelling theoretical advantage is metabolic dysfunction-associated steatohepatitis (MASH, formerly known as NASH) — fatty liver disease with inflammation and fibrosis.

Why glucagon matters for MASH. The glucagon receptor is expressed heavily in the liver. Glucagon receptor activation promotes hepatic fatty acid oxidation (burning fat stored in the liver), reduces de novo lipogenesis (new fat formation), and stimulates amino acid catabolism. These are precisely the metabolic pathways that are dysregulated in MASH. A compound that can directly activate hepatic glucagon signaling while simultaneously providing GLP-1-mediated appetite suppression and glycemic control is a targeted approach to the root metabolic dysfunction.

In the Phase 2 MASH trial, survodutide demonstrated significant improvements in liver histology. Approximately 47-64% of patients achieved MASH resolution (depending on dose) at 48 weeks, compared to 14% with placebo. Liver fibrosis improvement was also observed, though fibrosis endpoints require longer follow-up for definitive conclusions.

Tirzepatide is also being studied for MASH (SYNERGY-NASH trial), and GLP-1 agonism alone has shown liver benefits. However, the direct hepatic glucagon receptor activation gives survodutide a mechanistic rationale that tirzepatide's GIP co-agonism does not share.

Side Effect Profiles

Both compounds share the GLP-1 class side effects — nausea, vomiting, diarrhea, decreased appetite, and constipation. The differences lie in the co-agonist-related effects:

Tirzepatide: GI side effects are the primary tolerability concern. In SURMOUNT-1, nausea occurred in approximately 24-33% of patients (dose-dependent), and discontinuation rates due to adverse events were 4-7%. The GIP component does not add distinctive new side effects beyond the GLP-1 class profile. Tirzepatide is generally well-tolerated through slow dose titration.

Survodutide: The glucagon component introduces additional considerations. Elevated heart rate has been observed (glucagon has chronotropic effects). In Phase 2 trials, mean heart rate increased by 3-6 beats per minute. GI side effect rates were comparable to other GLP-1 agonists. Importantly, the glucagon-mediated blood glucose elevation appears to be adequately offset by the GLP-1 component — glycemic control was maintained or improved in trial participants.

The heart rate signal will be closely watched in Phase 3 trials. If confirmed, it could be a meaningful differentiator for patients with cardiac arrhythmia risk.

Approval Timeline and Availability

Tirzepatide: Already FDA-approved for type 2 diabetes (Mounjaro, 2022) and chronic weight management (Zepbound, 2023). Widely available with expanding insurance coverage. A known, accessible option today.

Survodutide: In Phase 3 clinical trials as of early 2026 (ACHIEVE program for obesity, SYMPHONY program for MASH). Developed by Boehringer Ingelheim. Earliest possible FDA approval is likely 2027-2028, depending on trial timelines and regulatory review. Not yet available outside of clinical trials.

For the other next-generation compound in this space, see our coverage of retatrutide, the first triple agonist (GLP-1/GIP/glucagon), which combines elements of both tirzepatide and survodutide. Our retatrutide Phase 3 analysis covers its clinical progress.

The Bottom Line

Tirzepatide and survodutide represent two different philosophies of multi-receptor metabolic intervention. Tirzepatide's GLP-1/GIP approach is proven, approved, and available — with the strongest weight loss data of any approved medication. Survodutide's GLP-1/glucagon approach is mechanistically compelling, particularly for MASH, but requires Phase 3 confirmation and is years from market availability.

For patients making treatment decisions today, tirzepatide is the actionable choice. For researchers and clinicians following the field, survodutide represents a potentially important expansion of the therapeutic toolkit — especially if its MASH data holds up in larger trials. The GLP-1 agonist class continues to diversify, and multi-receptor strategies are clearly the future of metabolic pharmacotherapy.