Peptide (Incretin) Drugs and the Liver

Who the players are. Two companies dominate the weight-loss and diabetes drug market. Novo Nordisk, of Denmark, makes semaglutide, sold as Ozempic for diabetes and Wegovy for weight loss. Eli Lilly, of Indianapolis, makes tirzepatide, sold as Mounjaro and Zepbound, which overtook Novo in 2025 to become the best-selling drug in the world at US$36.5B (Fierce Pharma, Feb 2026). Lilly's next drug, retatrutide, is not yet approved but has just completed its main obesity trials, with weight loss of up to 30% in its first Phase 3 (Pharmaceutical Journal, May 2026). These drugs are grouped as "incretins" because they copy incretin hormones, the gut signals that tell the body a meal has arrived. The best known of those hormones is GLP-1, which is why the drugs are often called GLP-1s.

Why this matters to Resonance. No sponsor of these drugs, whether Lilly, Novo, Boehringer, Sun Pharma or the dozens of smaller companies behind them, stops running trials when a drug is approved; each starts a different and larger set. Those trials measure many things Resonance has nothing to do with: heart attacks and strokes, blood sugar, blood pressure, kidney function, sleep apnoea scores, joint pain. But a growing share of them also need an organ imaged rather than a scale read, and for a weight-loss drug the organs that matter are the liver and the body's fat and muscle. Liver fat, liver scarring, visceral fat and muscle are the four MRI measurements those trials order. Today Resonance Health sells one of them as a regulatory-cleared product (liver fat, HepaFatScan) and offers visceral and subcutaneous fat to trial sponsors as a central-read service, commercial since FY25 (RHT investor presentation, 8 June 2026); its muscle measures and its liver-scarring (fibrosis) device are still in development and not cleared (IAG release, 23 Sep 2026). All of it runs from a standard MRI on any scanner, read centrally. This article sets out why that makes Resonance useful to any obesity-drug sponsor, where that usefulness could become hard to replace, and where the claim should not be pushed. Lilly appears often because it has the largest pipeline and the best public record of how it buys these measurements, not because the case depends on it; Resonance's largest customer today is Sun Pharma (Small Caps, 20 Nov 2024), and its new distribution channel reaches sponsors it has never met (IAG release, 23 Sep 2026).

Three facts carry the argument:

Approval would not end the trials. Lilly's tirzepatide (Mounjaro and Zepbound) sold US$36.5B in 2025 and Novo's semaglutide (Ozempic and Wegovy) about US$33B (Fierce Pharma, Feb 2026), and both franchises are still running Phase 3 and Phase 4 trials years after approval. That is how the system works. A Phase 3 trial is the large, multi-site study a regulator requires before a drug can be sold for a specific use, and each new use needs its own: approval for obesity does not cover MASH, sleep apnoea or heart disease, so a company that wants those on the label has to run a separate Phase 3 for each. Phase 4 trials come after approval and are often a condition of it: the FDA can require post-marketing safety studies, long-term outcome trials and, where a drug was approved on a surrogate marker such as liver fat, a confirmatory trial proving it actually prevents liver failure, which is the position both Rezdiffra and semaglutide for MASH are in today. Retatrutide approval would therefore close its obesity trials and open the MASH, muscle-preservation, label-expansion and head-to-head trials that follow, and the liver and body-composition arms of those trials need an organ imaged rather than a scale read. For Resonance that is more trial work, not less, and the detail is in section 05 below.

The one open question is Resonance's fibrosis device. Its Extended Proof of Concept (EPoC) trial is fully enrolled with analysis underway, and management said in late August 2026 that results were expected within about a month (earnings-call highlights, 4 Sep 2026). As of 7 October 2026 no result has been announced. If it separates F2 from F3 scarring, and the device is then cleared by regulators, Resonance could offer one MRI scan on any scanner, read centrally, covering fat, iron and fibrosis, with body-composition measures alongside. If it does not, the existing fat and body-composition business still rides the same wave.

A caution on the word "dependent". Lilly can buy liver fat and body composition imaging from several vendors, including Perspectum and the imaging CROs themselves. Resonance's case is not that Lilly cannot do without it. It is that, for the measurements it sells today, Resonance already has the harder pieces in place: regulatory clearances for liver iron and liver fat, a central read, a protocol that runs on any MRI scanner, and its own trial sites. The fibrosis product is not on the market. It has no clearance, and its EPoC results are still pending. Only a positive result followed by clearance would let Resonance offer fibrosis alongside fat and iron from one scan.

Fatty liver disease is staged by how much scar tissue the liver has, and that stage decides who gets a dedicated liver drug. This section explains the staging for a reader with no medical background, because the F2-versus-F3 line comes up throughout the rest of the report.

The plain-English version. The liver is the body's chemical factory. When someone carries extra weight or has type 2 diabetes, fat collects inside the liver. For most people that is harmless. In some, the fat irritates the liver, the cells become inflamed and injured, and the liver repairs itself the way skin does: with scar tissue. A little scar is fine. Keep injuring it for years and the scar accumulates until it chokes the organ, which is cirrhosis.

The names have changed recently, which causes confusion. NAFLD (non-alcoholic fatty liver disease) is now called MASLD. NASH, the inflamed form, is now called MASH. Same disease, new labels.

The first three steps can go backwards: lose enough weight, or take one of the new drugs, and fat clears, inflammation settles and scar can slowly remodel. Cirrhosis mostly cannot. That is why catching people at step 3, and watching whether they move forward or back, matters so much.

It also changes what Resonance's products are for. For most of its history the company pitched HepaFatScan as early detection, a painless scan that finds liver fat before the damage becomes irreversible, and its patient materials still talk about proactive imaging. The weakness of that pitch was that finding fat early led nowhere: until 2024 there was no drug to prescribe, so the clinical system had little reason to screen, and the scan was mostly ordered by drug trials and by specialists managing iron overload. The peptides remove that weakness. A liver found early now has a treatment to go to, and the same scan that found it is the one that shows whether the treatment is working six months later. Screening and therapy stop being separate ideas, and Resonance's old positioning and its new one become the same product used twice: once to find the patient, once to follow them.

The F scale. Doctors grade scar tissue on a five-point scale, F0 to F4, by looking at a biopsy sample under a microscope. "F" stands for fibrosis, the medical word for scarring. The scale is about how much scar there is and how it is arranged, not how the patient feels; most people at F2 or F3 feel completely well, which is why the disease is caught late.

The commercially important line sits between F1 and F2. Below it, the advice is lifestyle and weight loss. From F2 upward a patient is "at risk" and qualifies for a dedicated liver drug such as Rezdiffra, at US$47,400 a year, or semaglutide for MASH. F3 is the group most likely to tip into cirrhosis, so it is the group drug companies most want to find and treat. F4 is usually managed differently and excluded from MASH drug trials.

In the general fatty-liver population the at-risk group is small: published screening studies put F2 or worse at about 6% of screened adults and F3 at about 1.6%. Most people with fatty liver are F0 to F1, where there is less to treat. That makes the F2-versus-F3 call the pivotal one, and the one that non-invasive tests are measured against.

Until recently the only trusted way to make that call was a liver biopsy: a needle through the side, a tissue sample the size of a grain of rice, a small risk of bleeding, time off work, and a result that two pathologists often read differently. Biopsy also cannot be repeated every six months to see whether a drug is working. That gap between what the new drugs need and what biopsy can deliver is where MRI-based measurement sits.

MASLD is also the largest and fastest-growing disease segment of the liver diagnostics market, at about a third of an estimated US$40.5B global market in 2026.

Each drug adds one more hormone signal to the one before it, and the third one, glucagon, is the one that acts on the liver directly. All three are once-weekly injections built from gut and pancreatic hormones that the body already uses to manage food.

A few points are easy to get wrong:

A simple way to hold it: semaglutide makes you eat less, tirzepatide makes you eat less more strongly, and retatrutide makes you eat less and also burn more, with the liver doing much of the burning.

Read left to right: each drug keeps everything the one before it does and adds a hormone. Only the third hormone, glucagon, has a direct effect on the liver, and the only drug with it is not yet approved. Sales figures are 2025 reported revenue for the two approved franchises (Fierce Pharma, Feb 2026); the retatrutide range runs from estimates approaching US$15B a year (AJMC, Aug 2026) to Clarivate's US$30B by 2031 (Fierce Pharma, Jan 2026), so it is a forecast with a wide error bar, not a number.

The drugs do not just slow liver disease; the trial data shows they reverse it, and the measurements used to prove that were mostly MRI and biopsy.

The retatrutide liver-fat result is the one to notice. In the Phase 2 substudy the trial investigators specifically looked for a liver toxicity signal because glucagon targets the liver, and found none. Instead the drug cleared liver fat faster and more completely than semaglutide or tirzepatide have in comparable work. Those measurements came from MRI fat-fraction scans, the same kind of measurement Resonance's HepaFatScan makes.

Liver safety. Raised liver enzymes (ALT, AST) were seen in some retatrutide patients without symptoms, and doctors are advised to monitor liver blood tests. People with advanced liver disease were excluded from the Phase 2 work, so safety in cirrhosis is not established. The full Phase 3 safety data, over 80 to 104 weeks in thousands of patients, has not yet been published; the press releases so far are topline only. Rare but serious events listed by independent reviewers include raised liver enzymes, cardiac arrhythmias and pancreatitis.

Two points matter for a diagnostics company. First, a drug that can cause enzyme rises while also clearing liver fat needs a way to tell the two apart, which a direct liver measurement gives and a blood test does not. Second, every one of these programmes has a liver endpoint, and the biopsy-based ones (ESSENCE) took 72 weeks and a needle at each end, while the MRI-based ones (the retatrutide substudy) showed the effect at 24 weeks with no needle.

A liver drug costing US$47,400 a year makes a few hundred dollars of imaging easy to justify, and the imaging is needed at least three times per patient. For decades there was little point screening for liver scarring because there was nothing to offer. Rezdiffra (March 2024) and semaglutide for MASH (2025) changed that, and the retatrutide data suggests the next drug will be stronger again.

The demand comes from three moments in each patient's course:

The scale is real and recent. Madrigal put the diagnosed MASH population at roughly 460,000 patients in May 2026, up nearly 50% in two years, with more than 49,000 on Rezdiffra. About 3.2 million Americans have been prescribed Wegovy and roughly one in eight US adults have tried a GLP-1. Each of those is a liver that someone may want measured.

The regulator has taken a side. When the FDA accepted the first non-invasive Letter of Intent on 27 August 2025, it published its own statement rather than leaving it to the applicant. The director of its hepatology division said non-invasive studies could replace liver histology, and that evaluating therapies without repeated biopsies would help recruitment and speed drug development. Lilly, Novo Nordisk and Boehringer Ingelheim wrote letters of support for the application. That de-risks the whole category of non-invasive liver tests, not just the first entrant. The FDA was equally clear that acceptance is only the first step in a multi-year qualification.

Biopsy got better too. In December 2025 the FDA qualified PathAI's AI-assisted pathology read, which makes biopsy results more reproducible. It does not make biopsy repeatable or painless, so the monitoring case for imaging is untouched, but it gives sponsors a lower-friction way to keep their existing endpoint.

Approval of any of these drugs closes its pivotal trials and opens a larger set, so the opportunity for a company like Resonance grows rather than shrinks. Retatrutide is the clearest upcoming example, but the same holds for Novo's CagriSema and amycretin, Boehringer's survodutide and Sun's utreglutide. Most of what those trials measure (heart outcomes, blood sugar, blood pressure, kidney function, sleep and joint scores) is outside Resonance's field. The liver and body-composition questions are not, and they cannot be answered with a scale.

What a sponsor needs after approval. Lilly is the fullest public example: its pipeline lists eloralintide (an amylin agonist) as an add-on to weekly incretins and bimagrumab (a muscle-preserving antibody) in combination studies, and seven further retatrutide Phase 3 readouts across 2026 and 2027. Novo is running the same playbook with CagriSema, and Boehringer with survodutide in MASH. Each of those programmes carries endpoints that only imaging can supply:

Resonance's largest contract today is a Sun Pharma GLP-1 trial in MASH (section 07), and approval of any one drug adds Phase 3b, Phase 4 and competitor trials to the Australian pipeline rather than removing them. Three things would move Resonance from useful vendor to the one a protocol is built around: a positive EPoC result, which would make it the only supplier of fibrosis, fat, iron and body composition from one scan; a sponsor running the fibrosis device alongside biopsy in a live trial; and the muscle-quality measures reaching clearance. None has happened yet, and the limit of the claim is plain: the sponsors are US$10B-to-60B companies that use several imaging vendors each, and Lilly, Novo and Boehringer all backed FibroScan's FDA application. The industry will need these measurements in volume for a decade; Resonance holds the clearances and infrastructure to supply them; the fibrosis result decides whether it supplies all four or three.

Sponsors do not do this in-house. Lilly has the most complete public record, so it is used here as the worked example: in every published trial where it measured the liver or body fat by MRI, the scans went to an outside central reader, and the same two or three vendors keep appearing. Novo's ESSENCE trial used central pathology and imaging in the same way, and Sun Pharma's MASH trial uses Resonance itself (section 07). The list below is who Resonance is competing with for the next protocol, at any sponsor.

The incumbents are AMRA Medical, which supplies body composition and liver fat, the set Resonance is taking to market through IAG, and Philips' BioTel Research, the imaging core lab that read the retatrutide liver scans and plays the role IAG now plays for Resonance. Resonance's pitch is to replace or sit alongside them on the next protocol. The gap in that vendor set is a fibrosis grade from a standard MRI: SYNERGY-NASH still needed a biopsy for it, FibroScan reads stiffness from ultrasound, and AMRA measures fat and muscle, not scar. That gap is the only reason a sponsor already supplied by AMRA and BioTel would add a small Australian vendor, and SYNERGY-OUTCOMES, a four-year liver outcomes trial of retatrutide and tirzepatide now recruiting, is the kind of study where it would matter.

Resonance's largest contract today is a GLP-1 drug being tested in MASH patients, with liver fat and liver stiffness by MRI as the primary endpoints. This trial is a live example of the dynamic this article describes, running in Perth with Resonance doing the imaging.

RHT announced the contract in November 2024 as a A$13.8M, 24-month agreement to act as Australian sponsor and provide CRO, trial-site and imaging-analysis services for Sun Pharmaceutical's trial of an undisclosed "new drug compound". A trial registration on the Australian register names Sun Pharmaceuticals as sponsor, CRO Services Pty Ltd trading as Resonance Clinical as local sponsor, TrialsWest as the site and Prof John Olynyk, a Perth hepatologist, as principal investigator. RHT has not publicly tied the two together, but the match on sponsor, local sponsor, site and the 60-patient target reported in April 2026 is close enough to treat as the same study.

This trial shows the same dynamic: a GLP-1 peptide, a MASH population defined by F2 to F3 scarring, MRI liver fat and stiffness as the primary endpoints, and every Resonance service line in one protocol. It is Sun's second contract with Resonance after a A$6.3M agreement in 2023, and repeat business is better evidence of trust than any single result. A positive readout would add a published dataset in which Resonance's MRI reads were the primary endpoint of a GLP-1 MASH trial, the credential IAG can carry to other sponsors; a negative one would be the drug failing, not the yardstick. A larger Phase 2b or 3 would run across many countries, where only the imaging read could follow Resonance, and the revenue rolls off in H1 FY27 either way. The stiffness endpoint here is MR elastography, the method the fibrosis device is designed to replace, so a follow-on trial of this kind is where the device would first be used.

Most patients are filtered out cheaply; the expensive measurement is reserved for confirming the stage and then monitoring treatment, and those two steps are where MRI competes.

The funnel narrows fast. A GP sees many patients with obesity or diabetes; a blood score or FibroScan rules most of them out; only the minority who look like F2 or worse reach the confirmatory step. Two forces squeeze that step from both ends: FibroScan already sorts low from medium scarring cheaply enough to triage many patients, and a patient going on a GLP-1 for weight anyway may never need the F2-versus-F3 call. What those forces do not touch is the loop at the bottom: once someone is on a liver drug, a repeatable painless scan every 6 to 12 months has no cheap substitute.

Resonance already sells the liver-fat and body-composition measurements these trials use, and the fibrosis device would complete the set on a single scan. Everything it makes is software that reads a standard MRI: no extra hardware at the site, no contrast injection, analysed centrally in Perth under an ISO 13485 quality system.

The September 2026 alliance with Image Analysis Group makes these products orderable endpoints on IAG's DYNAMIKA platform, which has supported more than 700 trials. It has a 24-month initial term and is aimed at obesity, metabolic disease, MASH and iron-overload trials; the announcement does not state exclusivity, and nothing in it stops Resonance selling into other imaging-CRO networks as well. It gives Resonance global distribution without building an international sales force, and gives IAG's sponsors an Australian trial-delivery partner.

The fibrosis device. Earlier proof-of-concept work on 30 subjects confirmed a fibrosis signal, which RHT describes as separating a liver with no scarring (F0) from one with any scarring (F1 and above) (RHT investor presentation, 8 June 2026). That is the easier question. The EPoC trial (study name DEVIMLA), which enrolled 68 patients with biopsy as the reference standard (RHT investor presentation, 8 June 2026), is designed to answer the harder ones: separating F2 from F3, and reading inflammation and ballooning as a secondary endpoint. Management told the FY26 results webinar on 28 August 2026 that results were expected in the next month or so, with publication to follow, then investigational use inside pharma customers' trials, then an FDA submission built on that data. RHT’s FY26 Annual Report confirms that all MRI and biopsy data has been received and analysis is underway, with the readout expected early in FY27. As of 7 October 2026 no result has been announced, and the device has not yet been accepted into the FDA biomarker qualification process; RHT's roadmap lists CDER biomarker qualification and an FDA 510(k) pathway as FY27 steps (RHT investor presentation, 8 June 2026). Treat the silence as neither good nor bad; the company no longer files quarterly cash-flow reports, so news flow is quieter by design.

What a positive result would mean: one 15-minute scan on any installed MRI, read centrally, returning fat, iron, fibrosis grade and body composition together. For a sponsor running a retatrutide-class trial across dozens of sites, that removes the operator variability of FibroScan, the add-on hardware of MRE and the needle of biopsy in one order.

The table below sets the five options against the criteria a sponsor or clinician actually applies, with the reason each criterion matters.

Two rows carry the argument. "Repeatable every 6 months" is where biopsy drops out, and it is the row the peptides make matter most, because every treated patient now needs a follow-up. "Consistent across sites" is where FibroScan drops out, and it is the row a sponsor running sixty sites in twenty countries reads first. On design, the RHT platform is the only option without a red in either row; the device cells await EPoC, and the price is the open item. The "stages scarring" row is what EPoC has to fill in.

FibroScan (Echosens) and MR elastography (Resoundant) entered the FDA's biomarker programme in 2025, Perspectum's cT1 is already cleared and is the closest product to RHT's, PathAI's AI-assisted biopsy read was FDA-qualified in December 2025, blood panels such as ELF filter patients cheaply but cannot stage them, and AMRA Medical (Sweden) is Lilly's incumbent for MRI body composition and liver fat, the closest rival to Resonance's non-fibrosis products. Section 07 of the August investment review covers each of these in detail and this article does not repeat it.

A positive EPoC would put RHT in direct competition with FibroScan, and the contest is about distribution as much as accuracy. FibroScan has already won the clinic: with units installed in 127+ countries, the marginal scan is five minutes and a few hundred dollars, and no MRI slot can match that where the device is already sitting. Everywhere it is not sitting, the economics reverse. A sponsor running sixty sites in twenty countries has to make sure each one owns a FibroScan, has the right probe for obese patients, has a trained operator and stays calibrated, and every new site is a purchase, an install and a training cycle. Echosens does not publish prices, but the UK's NICE assessment of FibroScan lists a 430 Mini+ console at about £48,000, with probes adding roughly £16,700 and the fat-estimating CAP software £18,500, around £120,000 over seven years once service is included, and one NHS trust's published contract for a single FibroScan was £100,000. Call it £50,000 to 100,000 (US$60,000 to 130,000) per site depending on configuration, before the operator and calibration. Sixty sites that do not already own one is several million dollars of hardware before the first patient is scanned. RHT's product reads a sequence from an MRI the hospital already paid for, so a new site is a connection rather than a procurement, and the result is read in one core lab whoever ran the scanner. The same holds for a hospital network rolling out monitoring across a region. RHT's own constraint is MRI access, scanner time and remote sites without one, but the installed MRI base is many times the installed FibroScan base. FibroScan also holds an FDA head start with letters of support from Lilly, Novo Nordisk and Boehringer, and a stiffness reading that struggles to separate F2 from F3. So FibroScan keeps the clinics that already have one; RHT competes for trials, networks and new geographies, where its distribution cost is near zero and FibroScan's is per device. MRE is the more direct target still, since RHT would offer the same answer without the add-on hardware.

None of those rivals deliver fat, iron, fibrosis and body composition from one standard MRI with a central read, which is the combination an obesity sponsor's trial actually orders. Resonance would be the only vendor to do so if EPoC is positive; today it delivers fat, iron and body composition, not a cleared fibrosis grade.

The EPoC readout is overdue against management's own "next month or so" and is the single event that changes the picture; everything else is a slower confirmation that the platform business is riding the wave.

The retatrutide decision date is an estimate from a planned Q1 2027 submission plus a standard 10 to 12 month review; the trial roll-off date is management's approximate guidance. Signals, in rough order of impact:

Figures on Resonance Health, the competitive landscape, market sizing, drug pricing and the FDA's August 2025 statement are taken from the RHT Shareholder Investment Review, August 2026 and its full PDF, which cite RHT's FY26 Appendix 4E, Annual Report and results webinar of 28 August 2026, Madrigal SEC filings, FDA and Echosens announcements, and the papers listed there. Every link below was loaded and checked against the claim it supports on 7 October 2026. Two journal links (NEJM and Nature Medicine) block automated access; open-access copies are given alongside.

Notes on what this report does not do. It does not value RHT's shares; the investment review it draws on does that and states its own caveats. It does not cover retatrutide's non-liver safety profile beyond the gastrointestinal effects common to the drug class. Fibrosis-stage prevalence (about 6% F2 or worse, 1.6% F3) is from Harrison et al., Journal of Hepatology 2021, cited in the investment review and not re-opened here. All retatrutide Phase 3 figures are company topline releases; full peer-reviewed publications were not available as of 7 October 2026.

This article is general information only and is not financial advice. It does not consider your objectives, financial situation or needs. The author, Daniel Gouvignon, holds shares in Resonance Health (ASX:RHT) and is therefore not independent in the regulatory sense; this analysis reflects a shareholder's perspective and may be biased accordingly. The author is a long-term holder and will disclose any material change in position. It was not commissioned, reviewed or paid for by the company.

Nothing here is a recommendation about any drug. Retatrutide is investigational and not approved anywhere; the trial figures quoted are company topline releases, and the sales figures for it are analyst forecasts with a wide range. Figures on Resonance Health are as at 7 October 2026 and are not updated for later events; the EPoC readout was expected around the end of September 2026 and had not been announced at the time of writing. Micro-cap securities are illiquid and volatile. You can lose your entire investment. Do your own research and consider seeking advice from a licensed adviser before making any investment decision.