The metformin PMP trial at the University of California, Irvine is testing whether people with pseudomyxoma peritonei can take 850 mg of metformin a day for up to 18 months. It is a small, single-site study, and the main question right now is tolerability, not whether tumors shrink.

Members started asking about this trial within days of it showing up on ClinicalTrials.gov, and the question was almost always the same one. Why a diabetes pill.

It’s a fair thing to ask. Metformin has been in use since the 1950s, it costs almost nothing, and it has been pointed at a long list of cancers over the years without much coming of it. What makes this trial different is the research that came first.

What the metformin PMP trial actually is

The study is registered as NCT07693452. It opened in June 2026 at the Chao Family Comprehensive Cancer Center at UC Irvine. The principal investigator is Dr. Oliver S. Eng, a surgical oncologist who came to UCI from the University of Chicago, where he helped run one of the country’s leading peritoneal surface malignancy programs. The trial grew out of research from Dr. Eng and his colleagues at UCI.

Everyone who enrolls gets the drug. There is no placebo group. The dose is 850 mg by mouth once a day, which is lower than doses used to treat type 2 diabetes. Dr. Eng has described it as closer to what he called a prophylactic dose, chosen deliberately so side effects stay mild. Treatment runs up to 18 months, with scans at baseline and then every six months.

The trial is open to people with PMP from an appendiceal mucinous neoplasm who have recurrent or refractory disease after cytoreductive surgery and HIPEC, or unresectable disease, or who are not scheduled for surgery. Dr. Eng has confirmed that both low-grade and high-grade appendiceal mucinous neoplasms count. You are not eligible if your disease is resectable and surgery is already booked, if you are already taking metformin for something else, or if you have had a bad reaction to it before.

The research that pointed them here

Cells make energy in more than one way. Plenty of cancers are known for burning sugar fast and inefficiently, which is the version most of us have heard about. There’s another route, run inside the mitochondria, that’s slower and gets far more out of the same fuel. Different tumors lean on these routes in different proportions.

Dr. Eng’s group has spent roughly four years on how PMP tumors survive in the abdomen, where the blood supply is patchy and nutrients aren’t evenly available. Part of that has involved taking tumors removed during surgery and growing them in the lab. In 2023 the group published an analysis in Annals of Surgical Oncology comparing peritoneal tumors from low-grade appendiceal mucinous neoplasms against peritoneal tumors from adenocarcinoma. Using metabolomics and RNA sequencing, they found the two had distinctly different metabolic profiles, with differences in how they handle lipids, glutathione, and that mitochondrial energy route.

Metformin is known to interfere with that same mitochondrial process. If PMP turns out to be particularly reliant on it, then blocking it could slow these tumors down in a way it wouldn’t slow down a different cancer. That is a hypothesis, not a finding. The 2023 paper identifies metabolic differences and says plainly that more research is needed. It does not show that PMP depends on this pathway, and it does not test metformin.

On a recent webinar hosted by ACPMP, Dr. Eng said his lab has since seen what he called a significant response in tumor samples they grew. That is laboratory evidence, not evidence that metformin helps patients, and those results have not been published, so nobody outside his group can evaluate them yet. What they do explain is why his team moved from the lab into a clinical trial as quickly as they did.

What this study can and cannot prove

The primary endpoint of the metformin PMP trial is feasibility. Specifically, whether participants take at least 80 percent of their scheduled doses over the first six months. Patients track it in a pill diary and the drug is dispensed by the UCI pharmacy. That is the study’s primary measure.

A feasibility endpoint isn’t a disappointment. It’s how a first study is supposed to work, and it’s the step that earns funding for a larger one. It does mean this trial is not designed to tell anyone whether metformin shrinks mucin. There’s a secondary endpoint tracking progression-free survival with scans at 6, 12, and 18 months, so they will be watching. But fifteen people in a single-arm study with no comparison group can’t separate a drug effect from the natural pace of a disease that’s often slow to begin with. If someone’s scans hold steady for 18 months, we won’t know what to credit.

Some other limits. The published paper rests on eight tumor samples, which is small even by rare cancer standards. The laboratory data showing an actual metformin effect hasn’t been published. And metformin has been tested in other cancers, including ovarian and pancreatic, with mixed results. Dr. Eng said as much himself.

Then there’s geography. The metformin PMP trial has one site, in Orange, California, in the U.S. You have to be there in person to enroll, then again at 30 days, then every six months after that. Metabolic bloodwork is checked at baseline and at one month. Roughly a third of our community lives outside the United States, and I don’t yet have a straight answer on whether international patients can take part, or whether scans can be done closer to home. Those are two of the questions I’m putting to Dr. Eng directly.

Who this covers, and who it leaves out

The protocol is written around pseudomyxoma peritonei arising from appendiceal mucinous neoplasms. Goblet cell adenocarcinoma, signet ring cell disease, appendiceal neuroendocrine tumors, and non-mucinous appendiceal adenocarcinoma all sit outside what this particular study covers. So does PMP from a non-appendiceal origin.

If that’s you, I’ve asked Dr. Eng what he’d say to those patients and what his lab is working on next. He has described the metformin work as the tip of the iceberg and said his team has found other pathways in PMP that nobody has described before. I intend to get more out of him on that.

Common questions about the metformin PMP trial

Can I just ask my doctor to prescribe metformin instead of joining a trial?
Please don’t do that on the strength of this article. Nobody knows yet whether metformin helps PMP. Taking it outside a study means you carry the risk without adding to the answer. Talk to your oncologist.

Is 850 mg a high dose?
No. It’s lower than doses used to treat type 2 diabetes. Dr. Eng has said the lower dose was picked deliberately, since gastrointestinal side effects such as diarrhea and nausea are common with metformin and tend to be worse at higher doses.

Can I stay on my other treatment?
Potentially. Dr. Eng said the trial doesn’t automatically exclude patients who are on another treatment, including systemic chemotherapy, as long as there’s no problematic interaction. The UCI team reviews each patient’s medications during screening.

Is 15 patients a hard cap?
No. Dr. Eng said fifteen is the minimum recruiting target and that the trial is allocated for more than that.

How do I ask about joining?
The study team at UC Irvine can be reached at ucstudy@uci.edu or 877-827-8839. They can do a phone or video consultation first. You can also find this trial and everything else currently open for appendix cancer and PMP on the Appendicure trial finder.

Ask him yourself

Dr. Eng is joining me live on Monday, September 22 for a session built around the questions his earlier talks didn’t get to. What participation really costs, whether imaging can be done at home, whether patients outside the U.S. can take part, how metformin sits with a gut that’s been through cytoreduction, and what’s coming behind this trial. It’s free, it’s for patients and caregivers, and about half of it is live Q&A. Register here.

Sources: ClinicalTrials.gov record NCT07693452, last updated July 2026. Hanse E, Wang T, Tifrea D, Senthil M, Kim A, Kong M, Eng OS, “A Novel Assessment of Metabolic Pathways in Peritoneal Metastases from Low-Grade Appendiceal Mucinous Neoplasms,” Annals of Surgical Oncology, August 2023. Dr. Eng’s remarks are from the ACPMP educational webinar on this trial.