Survodutide and mazdutide: GLP-1/glucagon duals for liver fat
Survodutide (Boehringer Ingelheim/Zealand) and mazdutide (Innovent/Lilly) are GLP-1/glucagon dual agonists in late-stage clinical trials. Unlike tirzepatide (which pairs GLP-1 with GIP), these drugs pair GLP-1 with glucagon — a different metabolic axis with strong effects on hepatic fat content.
The glucagon angle
Glucagon is typically known as the "raise blood sugar" hormone. Chronically, glucagon receptor activation in liver and adipose tissue has different effects:
- Hepatic fatty-acid oxidation. The liver burns fat instead of storing it.
- Reduced hepatic lipogenesis. Less new fat synthesis.
- Modest increase in basal metabolic rate (~3–5%).
- Adipose tissue lipolysis, contributing to fat mobilization.
The fasting-glucose elevation that pure glucagon would cause is offset by the GLP-1 arm's insulin-secretagogue effect. Net glycemic control on a GLP-1/glucagon dual is comparable to GLP-1 alone.
Survodutide
Boehringer Ingelheim and Zealand Pharma. Status as of 2026: completing Phase 3 trials for obesity and MASH.
| Trial | Indication | Notable result |
|---|---|---|
| SYNCHRONIZE-1 | Obesity, Phase 2 | ~19% weight loss at top dose, 46 weeks |
| SYNCHRONIZE-2 | MASH, Phase 2 | ~83% MASH resolution at top dose vs ~18% placebo |
| SYNCHRONIZE-3 (ongoing) | Obesity Phase 3 | Expected primary completion 2026–2027 |
Survodutide's standout result is on liver-fat reduction in MASH patients — significantly better than semaglutide in the same indication.
Mazdutide
Innovent Biologics (Chinese pharma, partnered with Eli Lilly). Originally developed as IBI362.
| Trial | Indication | Notable result |
|---|---|---|
| GLORY-1 | Obesity (Chinese, Phase 3) | ~18.6% weight loss at top dose, 60 weeks |
| DREAMS-1 | T2D (Chinese, Phase 3) | HbA1c reductions comparable to dulaglutide |
Mazdutide received approval in China (June 2025) for chronic weight management in adults. U.S. and EU approvals are still pending; Lilly's involvement suggests parallel global development.
How they compare to existing GLP-1s
| Drug | Mechanism | Top dose weight loss | Liver fat reduction |
|---|---|---|---|
| Semaglutide 2.4 mg | GLP-1 only | ~14.9% | Modest |
| Tirzepatide 15 mg | GLP-1 + GIP | ~20.9% | Significant |
| Survodutide | GLP-1 + glucagon | ~18–19% | Strong (MASH resolution >80%) |
| Mazdutide | GLP-1 + glucagon | ~18.6% | Strong |
| Retatrutide 12 mg | GLP-1 + GIP + glucagon (triple) | ~24.2% | Very strong |
Where each fits
- For obesity with MASH or fatty liver disease: Survodutide and mazdutide are the strongest candidates. The glucagon arm directly addresses liver fat.
- For pure obesity without metabolic liver disease: Tirzepatide is similar in efficacy and is already approved. Survodutide/mazdutide may be slight overkill.
- For T2D: Tirzepatide remains the front-runner. Glucagon-containing duals don't have the same T2D-specific evidence yet.
- For the future of the class: Retatrutide's triple-agonist data suggests adding glucagon to GIP+GLP-1 is even better than any pairwise combination.
Side-effect profile
Similar GI profile to other GLP-1s — nausea, vomiting, diarrhea, constipation. Distinct considerations:
- Resting heart rate increases ~5–7 bpm sustained on glucagon-containing drugs. Worth tracking, especially in patients with cardiovascular history.
- Transient liver-enzyme elevations (ALT, AST) observed in early trials, usually resolving with continued therapy. Mechanism: increased fatty-acid flux through the liver.
- Fasting glucose needs monitoring in T2D patients on combined therapy with insulin or SUs.
When they'll be available
Mazdutide is approved in China; pending in U.S. and EU. Survodutide is in late Phase 3 with completion expected 2026–2027 for both obesity and MASH. Both will likely launch in 2027–2028 in major Western markets.
FAQ
Will survodutide or mazdutide replace tirzepatide?
For patients with concurrent liver fat issues — possibly. For pure obesity, tirzepatide is already approved and effective. The new drugs likely carve out the MASH-and-obesity niche.
Is mazdutide available in the US?
Not as of 2026. Approved in China. U.S. and EU pathways are in progress through Lilly's development arm.
Does the glucagon arm cause hyperglycemia in non-diabetic users?
No, the GLP-1 arm offsets it. Fasting glucose typically stays in range or improves in non-T2D users.
Is heart rate elevation a deal-breaker?
Not usually. A 5–7 bpm sustained increase is modest. Patients with significant cardiovascular history should discuss with their cardiologist before starting any glucagon-containing dual.
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