What is the recommended starting dose of Wegovy (semaglutide) for adults with metabolic‑dysfunction‑associated steatohepatitis (MASH) and moderate to advanced liver fibrosis (stage F2‑F3) without cirrhosis?

Starting Dose of Wegovy for MASH

Wegovy (semaglutide 2.4 mg) should be initiated at 0.25 mg subcutaneously once weekly, with dose escalation every 4 weeks following a fixed titration schedule: 0.25 mg (weeks 1-4) → 0.5 mg (weeks 5-8) → 1.0 mg (weeks 9-12) → 1.7 mg (weeks 13-16) → 2.4 mg maintenance (week 17 onward). 1, 2

FDA-Approved Indication and Patient Eligibility

Wegovy received conditional FDA approval in August 2025 for adults with non-cirrhotic MASH and moderate to advanced liver fibrosis (stages F2-F3), based on the ESSENCE trial demonstrating 62.9% MASH resolution and 36.8% fibrosis reduction at 72 weeks. 1, 3, 2

Eligible patients must have:

• MASH with stage F2 or F3 fibrosis (not F0-F1 or cirrhosis) 1, 3
• Identification via noninvasive tests rather than mandatory liver biopsy 1
• VCTE 8-15 kPa, MRE 3.1-4.4 kPa, or ELF 9.2-10.5 for F2-F3 fibrosis 1

Mandatory Titration Schedule

The slow 4-week escalation protocol is essential to minimize gastrointestinal adverse events (nausea 17-44%, diarrhea 12-32%, vomiting 7-25%). 4

Week	Dose (subcutaneous, once weekly)
1-4	0.25 mg
5-8	0.5 mg
9-12	1.0 mg
13-16	1.7 mg
17+	2.4 mg (maintenance)

4, 1

Absolute Contraindications Before Starting

Screen all patients for the following absolute contraindications before initiating therapy:

• Personal or family history of medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia type 2 (MEN 2) 4
• Pregnancy or breastfeeding 4
• Severe hypersensitivity to semaglutide 4
• Child-Pugh C cirrhosis 5

Relative Cautions Requiring Risk-Benefit Assessment

• Prior pancreatitis (use with caution) 4
• Symptomatic gallbladder disease (38% increased risk of cholelithiasis/cholecystitis vs placebo) 4
• Severe gastroparesis 4
• Child-Pugh B cirrhosis (cautious use only) 4, 5
• VCTE 15-20 kPa, MRE 4.4-5 kPa, or ELF 10.5-11.3 (requires exclusion of cirrhosis with confirmatory testing or platelet count >150,000/mm³) 1

Baseline Assessment Before First Dose

Obtain the following before initiating therapy:

• FIB-4 score and liver stiffness measurement to confirm F2-F3 fibrosis 4, 1
• HbA1c, fasting glucose, renal function (eGFR), liver enzymes (ALT/AST), lipid panel 4
• Platelet count (to exclude cirrhosis if borderline stiffness values) 1
• Screen for MTC/MEN 2 family history 4

Concomitant Medication Adjustments at Initiation

Make these adjustments when starting Wegovy to prevent hypoglycemia:

• Reduce basal insulin by 20% 4
• Reduce or discontinue sulfonylureas by 50% 4
• Stop all DPP-4 inhibitors (no additive benefit) 4
• Continue metformin, SGLT2 inhibitors, and statins 6, 4

Monitoring During Titration (Every 4 Weeks)

Assess the following at each dose escalation visit:

• Weight, blood pressure, gastrointestinal tolerance 4
• Signs of pancreatitis (severe abdominal pain) 4, 1
• Signs of gallbladder disease (right upper quadrant pain) 4, 1
• Dehydration risk (acute kidney injury prevention) 1

Treatment Response Evaluation at Maintenance Dose

Assess response at 12-16 weeks after reaching 2.4 mg maintenance dose:

• Discontinue if <5% weight loss at 3 months on maximum tolerated dose 4
• Significant improvement suggested by: ALT reduction >17 U/L or ≥20%, CAP reduction ≥30%, VCTE LSM reduction ≥30%, MRE LSM reduction ≥20%, or ELF reduction ≥0.5 1
• Non-response suspected if ALT or noninvasive tests worsen 1

Common Pitfalls to Avoid

Do not skip or accelerate the titration schedule—rapid escalation dramatically increases gastrointestinal adverse events and treatment discontinuation. 4, 7 Real-world data show 68.4% non-persistence when titration protocols are not followed, with mean time to discontinuation of only 24.8 weeks. 7

Do not use Wegovy in patients with cirrhosis (VCTE >20 kPa, MRE >5.0 kPa, ELF >11.3, or portal hypertension)—it is not FDA-approved for this population, though patients already receiving semaglutide for diabetes/obesity who develop compensated cirrhosis may continue with careful monitoring. 5, 1

Do not delay treatment waiting for liver biopsy—noninvasive tests are sufficient for patient selection and biopsy is impractical and unnecessary for most patients. 1

Combination Therapy Considerations

• Lifestyle modification (hypocaloric diet, 150-300 minutes/week moderate-intensity exercise) remains the cornerstone and must be continued alongside Wegovy. 1, 3
• Combination use with resmetirom at the 2.4 mg/week dose has not been studied. 1
• Pioglitazone may be added for additional metabolic benefit, though it lacks robust Phase III liver-specific data. 6

Long-Term Considerations

Plan for lifelong therapy when effective—abrupt discontinuation leads to rapid weight regain (50-67% of lost weight within one year). 4 Final FDA approval awaits demonstration of long-term clinical outcomes (hepatic decompensation, hepatocellular carcinoma, liver transplantation, death) beyond the 72-week interim data. 1, 2