Mazdutide vs. Tirzepatide vs. Survodutide: Glucagon Combos Compared

Mazdutide and survodutide add glucagon to the GLP-1 formula, a different approach from tirzepatide's GIP-plus-GLP-1 design. As of October 2026, tirzepatide (Zepbound, Mounjaro) is the only one of the three approved in the US, mazdutide is approved only in China, and survodutide is still investigational despite positive phase 3 results. On weight loss alone, the glucagon combos have not yet shown numbers that beat tirzepatide; their main promise is in the liver.

Three drugs, two strategies

All three are once-weekly injections that combine GLP-1 activity, which curbs appetite, with a second hormone signal.

• Tirzepatide pairs GLP-1 with GIP, another gut hormone. It is sold as Zepbound for weight management and sleep apnea, per its label, and as Mounjaro for type 2 diabetes. Mounjaro's label added a heart-protection indication in August 2026.
• Mazdutide is a GLP-1 and glucagon dual agonist and an analog of oxyntomodulin, a natural gut hormone that hits both receptors, per Innovent's approval announcement. It comes from Eli Lilly, which licensed China rights to Innovent Biologics in 2019 and kept rights elsewhere, according to Fierce Biotech.
• Survodutide is a glucagon and GLP-1 dual agonist from Boehringer Ingelheim, licensed from Zealand Pharma. It is investigational and not approved by any regulator, per Zealand's survodutide page.

Glucagon acts heavily on the liver, which is why both glucagon combos are being developed for fatty liver disease as well as obesity. The triple agonist retatrutide, which adds glucagon on top of GIP and GLP-1, is a separate story we cover in our retatrutide preview.

Head-to-head table (cross-trial)

Cross-trial comparison: different populations, durations, and analysis methods. Sources: Innovent (GLORY-1), Clinical Trials Arena (DREAMS-2), AJMC (SYNCHRONIZE-1 and -2), Zepbound label, Zealand Pharma H1 2026 report, Zealand Pharma newsroom, Lilly pipeline.

Why the weight-loss numbers do not line up neatly

GLORY-1 enrolled 610 Chinese adults with overweight or obesity and ran 48 weeks. Counting everyone who started, weight fell 11.0% on 4 mg and 14.0% on 6 mg versus a 0.3% gain on placebo, according to Innovent's announcement of the NEJM publication. Results from a single-country trial may not carry over exactly to other populations. The trial also tested 4 mg and 6 mg doses, while an earlier phase 2 cohort on 9 mg showed 15.4% placebo-adjusted loss at just 24 weeks, per Fierce Biotech. Higher-dose phase 3 data could change the picture.

For survodutide, the "up to" figures are top-dose results at 76 weeks using the efficacy estimand, which estimates weight loss as if everyone stayed on treatment, according to AJMC. Tirzepatide's 20.9% comes from its US label and counts everyone who started treatment, including people who stopped, so it is the more conservative way of counting.

Where the glucagon combos might win: the liver

The clearest case for adding glucagon is fatty liver disease. In the phase 3 SYNCHRONIZE-MASLD trial, survodutide met its primary endpoints, and 6 in 10 people on it reached normal liver fat levels, according to Zealand's first-half 2026 report.

Survodutide also holds FDA Fast Track and Breakthrough Therapy designations for noncirrhotic MASH with moderate or advanced fibrosis, and two phase 3 MASH trials (LIVERAGE and LIVERAGE-Cirrhosis) are underway, per Zealand. If it succeeds in biopsy-based MASH trials, it could compete with the two drugs already approved for MASH, Wegovy and Rezdiffra.

Mazdutide also lowered liver fat in GLORY-1. Among participants who started with at least 10% liver fat, it fell by about 66% on 4 mg and 80% on 6 mg, versus about 5% on placebo. Mazdutide also reduced blood pressure, cholesterol, triglycerides, uric acid, and liver enzymes, according to Innovent.

Muscle, side effects, and other open questions

A frequent worry with powerful weight-loss drugs is losing muscle along with fat. For survodutide's top dose in SYNCHRONIZE-1, Zealand reported that lean mass made up no more than 11.3% of the total tissue lost, a figure it revised upward from 10.8% after recalculating the data, per its first-half 2026 report. That suggests most of the weight lost was fat, though independent analysis of the full data is still needed.

On tolerability, the evidence is uneven. Tirzepatide's label gives detailed rates: nausea in 25% to 29% of people across doses and side-effect discontinuations of 4.8% to 6.7%, per the Zepbound label. Survodutide's side effects stand out more: in SYNCHRONIZE-1, 17.8% (3.6 mg) and 20.2% (6.0 mg) of participants stopped because of gastrointestinal effects, versus 2.9% on placebo, per AJMC. Comparable US label data for mazdutide do not exist because it has not been reviewed by the FDA.

Heart outcomes are another gap. Tirzepatide now has a heart label through Mounjaro. Survodutide's SYNCHRONIZE-CVOT trial results are expected later in 2026, according to Zealand. We did not find a published cardiovascular outcomes trial for mazdutide.

If you have type 2 diabetes

Weight loss tends to be smaller in people with type 2 diabetes. Survodutide's top-dose result fell from up to 16.6% without diabetes to up to 13.1% with it in SYNCHRONIZE-2, which was published in NEJM on October 1, 2026. HbA1c fell by up to 1.21 points, versus 0.03 with placebo, per AJMC.

Mazdutide has the most detailed diabetes data of the two glucagon combos. In the 28-week DREAMS-2 trial of 731 Chinese adults already on metformin or other oral diabetes drugs, mazdutide lowered HbA1c by 1.69 points (4 mg) and 1.73 points (6 mg), versus 1.36 with dulaglutide (Trulicity), according to Clinical Trials Arena. Far more people on mazdutide reached both an HbA1c under 7% and at least 5% weight loss: 50% to 64%, versus 19% on dulaglutide.

Tirzepatide, meanwhile, is already an approved diabetes drug as Mounjaro, and since August 2026 its label includes reducing the risk of heart attack, stroke, and cardiovascular death in adults with type 2 diabetes at high risk. For someone with diabetes and heart risk, that proven outcome benefit is a meaningful advantage over drugs that have not finished outcome trials.

Can you get mazdutide or survodutide?

In the US, no, except through clinical trials. Mazdutide is approved in China for chronic weight management, according to Innovent's June 2025 announcement, but Lilly's public pipeline page did not list mazdutide as of October 2026. The page notes that some molecules are not disclosed for competitive reasons, so this does not confirm Lilly has dropped it. Survodutide has no regulatory approval anywhere, and we found no published filing timeline.

Sources

1. Zepbound (tirzepatide) prescribing information
2. Mounjaro (tirzepatide) prescribing information
3. Innovent: Mazdutide approved by China's NMPA for chronic weight management (June 2025)
4. Innovent: GLORY-1 phase 3 results published in NEJM (May 2025)
5. Fierce Biotech: Next-gen Lilly obesity drug slashes weight in Innovent study
6. Clinical Trials Arena: Innovent shows mazdutide efficacy at EASD 2024
7. Zealand Pharma: Survodutide pipeline page
8. Zealand Pharma: Financial results for the first half of 2026
9. Zealand Pharma newsroom (October 1, 2026 survodutide phase 3 announcement)
10. AJMC: Survodutide delivers up to 13.1% weight loss in type 2 diabetes (October 2026)
11. Eli Lilly: Research and development pipeline

Medical disclaimer: This article is general information, not medical advice, and does not replace a licensed clinician who knows your history. Approvals, labels, coverage and prices change; check the linked sources and talk with your prescriber or pharmacist before making decisions about any medication.