Hepatic steatosis: what the MASH trial evidence supports

Hepatic steatosis: what the MASH trial evidence supports — setting out what I have, and where I think it stops being reliable.

Asking about a population rather than about a person.

The published trials in this class mostly enrolled a fairly specific group, and the questions here frequently come from people well outside it. I would like to understand what the honest position is when someone falls outside the studied population: not "it is fine" and not "there is no data", but what the reasoning actually looks like.

Picking up the opening post: that is the part I would want checked first.

Multiple comorbidities: a person with diabetes, kidney disease, and cardiovascular disease is outside the studied populations in most trials. Extrapolating to that person requires reasoning from the individual component trials and mechanisms.

On the opening post — agreed on the reasoning, with one qualification.

Bariatric surgery history: altered anatomy after surgery affects absorption. That matters for oral medications and for reconstituted solutions. Discussing specific medications and doses with a clinician familiar with bariatric surgery is prudent.

PCOS and metabolic overlap: polycystic ovary syndrome has metabolic overlap with obesity and insulin resistance. Data on compounds in this class in PCOS specifically is thin; most discussion is by mechanism.

Cardiovascular disease: several compounds have cardiovascular outcome trials. SELECT was in people without diabetes; SUSTAIN 6 was in high-risk diabetes. Absolute benefit is largest in high-risk people.

Obstructive sleep apnoea: SURMOUNT-OSA used an objective endpoint, the apnoea-hypopnoea index. Reduction was substantial. Whether the benefit is weight loss or a direct drug effect is not resolved by the trial.

Worth separating two things that post #3 runs together.

Chronic kidney disease: compounds in this class have renal benefit in people with kidney disease. The benefit appears to be additive to other renal-protective agents, not a replacement for them.

post #7 is right about the mechanism and I think understates the practical bit.

Thank you for the correction. I have edited my earlier post with a note rather than silently, so the thread still makes sense to read. The error was mine and it was the kind that comes from remembering a figure instead of looking it up.

Type 2 diabetes: the population with the largest evidence base for these compounds. The SURPASS and SUSTAIN programmes established glycaemic benefit. The renal and cardiovascular benefit evidence is separate from the glycaemic benefit evidence.

Comorbidity control: if a comorbidity (high blood pressure, high lipids) is not adequately controlled, the decision about adding compounds in this class depends on the current control status, not on the compound alone.

Picking up post #8: that is the part I would want checked first.

I disagree with the reply above, and I think the disagreement is substantive rather than terminological.

The distinction being drawn does not survive when you look at the published data for this specific question. I would be glad to be shown wrong on this, because the version I am arguing against is more convenient.

Hepatic steatosis and MASH: a phase 2 trial in semaglutide for steatohepatitis showed resolution was more frequent on treatment. Histological resolution is a surrogate for long-term clinical outcomes like cirrhosis.

PCOS and metabolic overlap: polycystic ovary syndrome has metabolic overlap with obesity and insulin resistance. Data on compounds in this class in PCOS specifically is thin; most discussion is by mechanism.

Bariatric surgery history: altered anatomy after surgery affects absorption. That matters for oral medications and for reconstituted solutions. Discussing specific medications and doses with a clinician familiar with bariatric surgery is prudent.