Liver enzymes on GLP-1 therapy: ALT, AST, ALP and bilirubin, the ranges, fatty liver, and the Wegovy MASH indication

The liver tests come free with the comprehensive metabolic panel, and in people starting GLP-1 therapy they are abnormal more often than any other group of tests on it. That is not usually because of the drug. It is because the condition that brings most people to therapy, excess weight, is also the commonest cause of fat in the liver, and fat in the liver leaks enzymes.

The four tests

ALT (alanine transaminase) is an enzyme concentrated in liver cells. When cells are injured it spills into the blood. MedlinePlus gives 4 to 36 U/L. It is the single most useful liver number because little else releases it.

AST (aspartate aminotransferase) is in liver cells too, but also in muscle and heart. MedlinePlus gives 8 to 33 U/L. A raised AST with a normal ALT often points away from the liver: a hard workout the day before the draw will do it.

Alkaline phosphatase (ALP) comes from the bile duct lining and from bone. MedlinePlus lists 20 to 130 U/L on the CMP page. A high ALP with a high bilirubin suggests bile is not flowing, which is the pattern of a stone in the duct.

Total bilirubin is the pigment left over from recycled red cells; the liver processes it into bile. MedlinePlus gives 0.1 to 1.2 mg/dL. A mildly raised bilirubin with everything else normal is often Gilbert syndrome, a harmless inherited trait.

MedlinePlus notes for every one of these that normal ranges vary among laboratories. Upper limits for ALT in particular differ noticeably from lab to lab.

Why they are drawn before therapy

The ADA lists them. Liver function tests are part of the comprehensive medical evaluation in the Standards of Care for people with diabetes.

Fatty liver is common in the people being treated. A prescriber who sees an ALT of 55 before therapy wants to know whether it comes down as weight comes off, and needs the 55 to know that.

Because of the MASH indication. The Wegovy label now includes an indication for the treatment of noncirrhotic metabolic dysfunction-associated steatohepatitis (MASH, formerly NASH) with moderate to advanced liver fibrosis, consistent with stages F2 to F3, in adults. The label states the indication is approved under accelerated approval based on improvement of MASH and fibrosis, with continued approval contingent on confirmatory evidence. That indication is made on a liver work-up (imaging or biopsy for fibrosis stage), not on an ALT. But it means that for some people the liver is the reason for the prescription, and the enzymes are part of how the prescriber tracks it.

The same label reports, from the MASH trial, that lipase increases greater than three times the upper limit of normal occurred in 4.7% of Wegovy-treated patients versus 1.3% on placebo. That is a pancreatic enzyme, not a liver one, but it was measured in the liver trial and the lipase page covers what to make of it.

What the labels do not say

None of the four labels (Wegovy, Ozempic, Zepbound, Mounjaro) asks for routine liver enzyme monitoring, lists hepatotoxicity as a warning, or restricts use for a mildly raised ALT. The labels do describe gallbladder disease (cholelithiasis, cholecystitis) as an adverse reaction, and a stone that blocks the bile duct raises ALP and bilirubin. So when liver tests change on therapy, the gallbladder is one of the first things a clinician thinks about; the gallbladder imaging page covers the label language and when an ultrasound is done.

How often

• Baseline: on the initial CMP.
• If abnormal at baseline: the interval your prescriber sets, often three to six months, to see the direction of travel with weight loss.
• If you take a statin: with the lipid panel after a dose change and then yearly, which is the ADA schedule for statins.
• If you have MASH: the schedule your liver clinician sets, which will include a fibrosis assessment and is not an ALT alone.
• Trigger: pain under the right ribs, dark urine, pale stools, yellow eyes. Check now, along with the gallbladder work-up.
• Otherwise: with the annual panel.

What to discuss with your prescriber

• If your ALT is raised: what the likely cause is, whether anything else needs checking (alcohol, other medicines, hepatitis serology, iron), and when to repeat.
• Whether a fibrosis estimate (a FIB-4 score is calculated from age, AST, ALT and platelets you already have) is worth doing, given that MASH is now an indication.
• Which symptoms should prompt an early check.

The network's science site explains the mechanism behind GLP-1 effects on the liver. For product questions, FormBlends' semaglutide page describes its compounded program; compounded semaglutide is not FDA approved and does not carry the MASH indication or any other label indication.