Are Mounjaro (tirzepatide) and Trulicity (dulaglutide) in the same drug class, and could Mounjaro be responsible for the mild elevation in aspartate aminotransferase (AST) and alanine aminotransferase (ALT)?

Mounjaro and Trulicity: Drug Class and Liver Enzyme Considerations

Drug Class Classification

Yes, Mounjaro (tirzepatide) and Trulicity (dulaglutide) are both in the incretin-based therapy class, though with an important distinction. Trulicity is a selective GLP-1 receptor agonist, while Mounjaro is a first-in-class dual GIP/GLP-1 receptor co-agonist 1, 2, 3. Both medications work through incretin pathways to stimulate insulin secretion and reduce glucagon release in a glucose-dependent manner 1, 4.

Liver Enzyme Elevation Assessment

Your Current Laboratory Values

Your AST of 56 IU/L and ALT of 50 IU/L represent mild elevations (<5× upper limit of normal), classified as Grade 1 hepatocellular injury 5. Using sex-specific reference ranges (29-33 IU/L for males, 19-25 IU/L for females), these values are approximately 1.7-2.8× the upper limit of normal 5.

Likelihood of GLP-1 Medication Causation

GLP-1 receptor agonists, including both Mounjaro and Trulicity, rarely cause clinically significant liver enzyme elevations and are generally considered hepatically safe. In fact, these medications may actually improve liver enzymes in patients with non-alcoholic fatty liver disease (NAFLD) by addressing underlying metabolic dysfunction 1, 5. The SURPASS clinical trials of tirzepatide showed no increased hepatotoxicity signals, with adverse events primarily limited to gastrointestinal symptoms 3, 4.

Most Likely Alternative Causes

Your mild transaminase elevation is far more likely attributable to:

• Metabolic syndrome/NAFLD: The most common cause of mild ALT elevation, particularly if you have obesity, diabetes, hypertension, or dyslipidemia 5
• Medication-induced liver injury: Other medications account for 8-11% of cases with mildly elevated liver enzymes 5
• Alcohol consumption: Even moderate intake (≥14-21 drinks/week for men, ≥7-14 drinks/week for women) can cause this pattern 5
• Viral hepatitis: Chronic hepatitis B or C commonly presents with fluctuating transaminase elevations 5

Recommended Diagnostic Approach

Immediate Actions (Week 0)

• Repeat liver function tests in 2-4 weeks to establish trend and confirm persistence 5
• Calculate FIB-4 score using age, ALT, AST, and platelet count to assess fibrosis risk 5
• Complete liver panel: Include alkaline phosphatase, GGT, total/direct bilirubin, albumin, and PT/INR 5
• Viral hepatitis serologies: HBsAg, anti-HBc IgM, anti-HCV 5
• Iron studies: Ferritin and transferrin saturation to screen for hemochromatosis 5
• Metabolic assessment: Fasting glucose/HbA1c and lipid panel 5
• Detailed alcohol history: Use quantitative tools like AUDIT 5
• Comprehensive medication review: Check all drugs (including over-the-counter and supplements) against LiverTox® database 5

First-Line Imaging

• Abdominal ultrasound (sensitivity 84.8%, specificity 93.6% for moderate-to-severe steatosis) to identify hepatic steatosis, biliary obstruction, focal lesions, or portal hypertension 5

Management Thresholds

Continue Current Medications If:

• ALT remains <3× ULN (approximately <90 IU/L for men, <75 IU/L for women) 5
• No evidence of synthetic dysfunction (normal albumin, bilirubin, INR) 5
• FIB-4 score <2.67 5

Urgent Hepatology Referral If:

• ALT increases to ≥5× ULN (≥145-165 IU/L for males, ≥95-125 IU/L for females) 5
• ALT ≥3× ULN plus total bilirubin ≥2× ULN (Hy's Law pattern) 5
• FIB-4 score >2.67 indicating high risk for advanced fibrosis 5
• Liver enzymes remain elevated ≥6 months without identified cause 5

Critical Pitfalls to Avoid

• Do not discontinue your GLP-1 medications based solely on these mild elevations—they are unlikely to be the cause and may actually be beneficial for underlying NAFLD 1, 5
• Do not assume mild elevation is benign without proper evaluation—even modest increases can reflect significant pathology 5
• Do not overlook alcohol consumption—moderate intake can mimic NAFLD and should be addressed with complete abstinence 5
• Do not forget to calculate FIB-4 score—this simple tool identifies patients needing urgent specialist assessment 5

Bottom Line

Your mild liver enzyme elevations are almost certainly not caused by Mounjaro or Trulicity. These medications belong to the same therapeutic class (incretin-based therapies) and have excellent hepatic safety profiles 1, 3, 4. The most likely explanation is underlying NAFLD or another metabolic condition, which ironically may improve with continued GLP-1 therapy 1, 5. Complete the diagnostic workup outlined above while continuing your current diabetes medications, and only consider medication changes if ALT rises to ≥3× ULN or other concerning features develop 5.