Does glucagon agonism raise blood sugar?

On its own it would. In these compounds the GLP-1 component offsets it, and the balance between the two activities is a deliberate design parameter.

Is mazdutide available outside China?

No. It holds Chinese approval but no US or EU authorisation.

What is oxyntomodulin?

A naturally occurring gut peptide that activates both GLP-1 and glucagon receptors. It is the biological precedent this drug class is built on.

Glucagon Agonists: Survodutide and Mazdutide

The short answer

Survodutide and mazdutide are GLP-1/glucagon dual agonists. Adding glucagon-receptor activity increases energy expenditure and mobilises hepatic fat, which is why both have been studied in metabolic liver disease alongside obesity. Mazdutide is approved in China; survodutide remains investigational with Phase 3 data reported.

Key facts

Survodutide: BI 456906 (Boehringer Ingelheim / Zealand Pharma)
Mazdutide: IBI362 (Innovent / Eli Lilly)
Class: GLP-1 / glucagon dual receptor agonists
Mazdutide status: Approved in China; not US or EU
Mazdutide Phase 3: ~20% reduction on 9 mg
Additional target: Hepatic fat / metabolic liver disease

Why adding glucagon seems backwards

Glucagon raises blood glucose, so deliberately activating its receptor in people with metabolic disease looks like the wrong direction. The resolution is that glucagon does more than mobilise glucose: it increases resting energy expenditure and drives hepatic lipid oxidation. When paired with sufficient GLP-1 agonism, the glucose-raising effect is offset while the energy-expenditure and liver-fat effects remain. The balance between the two activities is the central design problem.

Survodutide

Survodutide, developed by Boehringer Ingelheim with Zealand Pharma under the code BI 456906, is a GLP-1/glucagon dual agonist. Its Phase 2 programme reported reductions in liver fat that positioned it as a candidate in metabolic dysfunction-associated steatohepatitis as well as obesity, and it has progressed into Phase 3 including a cardiovascular outcomes study and a Japanese programme registered as SYNCHRONIZE-JP.

Research material referenced

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Mazdutide

Mazdutide, developed by Innovent Biologics in collaboration with Eli Lilly under the code IBI362, is a GLP-1/glucagon dual agonist derived from oxyntomodulin. Phase 3 work in Chinese adults with obesity reported approximately 20% weight reduction on the 9 mg dose. It has been approved in China but holds no authorisation in the United States or European Union, and further trials continue across obstructive sleep apnoea and type 2 diabetes remission.

Where the glucagon arm may matter most

The distinguishing claim for this class is not weight reduction alone, since retatrutide and CagriSema report larger figures. It is the direct effect on hepatic fat. Metabolic liver disease is a large and poorly served indication, and a compound that addresses liver fat and body weight together has a different clinical case from one that addresses weight alone.

How this relates to retatrutide

Retatrutide contains glucagon-receptor agonism as one of its three activities, so it shares this mechanism rather than competing with it. The difference is that retatrutide adds GIP on top, making it a triple rather than dual agonist. Studying the duals in isolation is part of how the field works out how much each receptor contributes.

Frequently asked questions

Does glucagon agonism raise blood sugar?: On its own it would. In these compounds the GLP-1 component offsets it, and the balance between the two activities is a deliberate design parameter.
Is mazdutide available outside China?: No. It holds Chinese approval but no US or EU authorisation.
What is oxyntomodulin?: A naturally occurring gut peptide that activates both GLP-1 and glucagon receptors. It is the biological precedent this drug class is built on.

Extended research context

The GLP-1 & Incretin Science deep dive

Deep dive: the two routes to a bigger effect

Every compound trying to beat GLP-1 alone has taken one of two routes. The first adds more receptors from the same hormone family: GIP in tirzepatide, GIP and glucagon in retatrutide. The second adds a non-incretin satiety hormone, which in practice means amylin: CagriSema combines cagrilintide with semaglutide, and amycretin engages both receptors from one molecule. Both routes work, because they recruit signalling pathways that do not fully overlap. Neither has escaped the constraint that binds all of them, which is that gastrointestinal tolerability worsens as effect size grows.

Deep dive: why a percentage is not a result

The most-quoted numbers in this field are the least comparable. REDEFINE 1 reported 22.7% and 20.4% for the same compound in the same trial, the first among participants who adhered to treatment, the second across everyone randomised. TRIUMPH-1 reported 28.3% in an uncomplicated obesity population while TRIUMPH-3 reported up to 22.6% in adults with established cardiovascular disease, using the same compound. Before any two figures can be compared they have to match on estimand, population, duration, comparator and whether the number is placebo-adjusted. Most published comparisons match on none of them.

Deep dive: what happens after the trial stops

Every headline figure describes weight while treatment continues. The STEP-1 extension found that a year after semaglutide was stopped, participants had given back roughly two-thirds of what they lost, moving from 17.3% mean reduction to a net 5.6%, though average weight remained below baseline and nearly half stayed at least 5% down. Meta-analysis puts regain at around 0.8 kg per month. This is why maintenance studies such as TRIUMPH-6 matter more to the field's future than another two points of peak reduction.

Research applications

▸Comparing incretin and amylin compounds on a like-for-like basis
▸Interpreting estimands, thresholds and placebo-adjusted figures in trial reports
▸Tracking the obesity pipeline across sponsors and jurisdictions
▸Understanding receptor pharmacology behind GLP-1, GIP, glucagon and amylin
▸Distinguishing licensed medicines from investigational compounds

Handling checklist

✓Identify which estimand a quoted percentage comes from before citing it
✓Check the trial population and baseline BMI against the comparison you are making
✓Confirm the duration and whether the reduction curve had plateaued
✓Read discontinuation rates alongside efficacy figures
✓Verify every NCT identifier against ClinicalTrials.gov rather than secondary reporting

Common research-handling mistakes

Learnt from thousands of researcher orders across our UK labs.

✗ Comparing headline percentages across different trials

Fix: Population, duration, estimand and comparator all differ; the numbers are not interchangeable.

✗ Quoting the larger of two figures from the same trial

Fix: Name the estimand. Efficacy and treatment-policy answer different questions.

✗ Treating peak reduction as a durable outcome

Fix: Substantial regain follows cessation across the class; peak figures describe a maintained state.

✗ Assuming an oral route means a weaker mechanism

Fix: Route and receptor count are independent. Orforglipron is weaker because it hits one receptor, not because it is a tablet.

✗ Reading investigational compounds as available treatments

Fix: Most of this pipeline holds no authorisation anywhere; mazdutide is approved only in China.

Continue researching

Peer-reviewed guides, comparators and matched reference materials.

Primary sources & clinical trials

Peer-reviewed research and registered trials from PubMed, ClinicalTrials.gov, PubChem, FDA and NIH. All links open in a new tab and point to the primary source, so every claim can be verified at origin.

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Glucagon-Containing Dual Agonists: Survodutide and Mazdutide