SEMAGLUTIDE INJ,SOLN
Clinical Criteria Summary
Document 233: Semaglutide WEGOVY for weight management CFU
Exclusion Criteria
- Known pregnancy
- Lactating
- Type 1 diabetes (unless followed by a diabetes/weight management specialist for careful supervision)
- Personal or family history of medullary thyroid carcinoma or Multiple Endocrine Neoplasia syndrome type 2
- Severe gastrointestinal dysmotility, including gastroparesis
- History of pancreatitis (does not pertain to patients for whom the cause is known and no longer presents a risk)
- Known PDR, severe NPDR, clinically significant ME, or DME unless risks/benefits have been discussed with the patient and documented in the EHR with monitoring plans and follow-up with an eye specialist who is informed at initiation
Inclusion Criteria
- Documented participation in a comprehensive lifestyle intervention (CLI) that targets all three aspects of weight management: diet, physical activity, behavioral changes (within the past year on at least one occasion/visit)
- BMI is greater than or equal to 27 kg/m2 with at least one weight-related comorbidity (examples include hypertension, type 2 diabetes, prediabetes, dyslipidemia, metabolic syndrome, obstructive sleep apnea, osteoarthritis, metabolic dysfunction-associated steatotic liver disease, and heart failure with preserved ejection fraction)
- Indicated to reduce a secondary cardiovascular event in people with previous myocardial infarction, previous stroke, or symptomatic peripheral arterial disease (defined as: intermittent claudication with ankle–brachial index <0.85, peripheral arterial revascularization procedure, or amputation due to atherosclotic disease) in people with overweight or obesity
- Consideration of discontinuing medications that may precipitate weight gain if clinically appropriate
Additional Inclusion Criteria
- For females who can become pregnant: Pregnancy should be excluded prior to receiving and there should be contraceptive counseling on potential risks vs. benefits of treatment if she were to become pregnant
Document 410: Semaglutide WEGOVY Conversion Guidance
Indication & Primary Use
- Primarily indicated for patients requiring weight management.
- Semaglutide (OZEMPIC) should not be used for weight management alone.
Formulary Status & Preference
- Available non-formulary with criteria for use in weight management.
- No preference for semaglutide (WEGOVY) over liraglutide (SAXENDA).
- Conversion from liraglutide (SAXENDA) is not necessary for patients who are doing well and losing weight.
Conversion Criteria: Liraglutide (SAXENDA) to Semaglutide (WEGOVY)
- Suggested conversion doses are off-label; selection of a more conservative dose may be considered only if clinically appropriate on a case-by-case basis.
- Conversion dose and/or titration may need adjustment based on tolerability and glucose control in patients with T2DM.
- For patients currently on 3.0 mg daily liraglutide: Initiate 0.5 mg subcutaneous once weekly for 4 weeks, then 1.0 mg subcutaneous once weekly for 4 weeks, then 1.7 mg subcutaneous once weekly for 4 weeks, followed by 2.4 mg subcutaneous once weekly for maintenance.
Conversion Criteria: Semaglutide (OZEMPIC) to Semaglutide (WEGOVY)
- For patients currently receiving semaglutide (OZEMPIC) 1.0 mg subcutaneous once weekly for T2DM: Initiate 1.0 mg subcutaneous once weekly for a total of 4 weeks (combining OZEMPIC and/or WEGOVY), then 1.7 mg subcutaneous once weekly for 4 weeks, followed by 2.4 mg subcutaneous once weekly for maintenance.
- For patients receiving semaglutide (OZEMPIC) 2.0 mg subcutaneous once weekly: Consider conversion to 2.4 mg subcutaneous once weekly only if the patient has received the 2.0 mg dose for at least 4 weeks.
- When switching from semaglutide (OZEMPIC) once weekly to semaglutide (WEGOVY) once weekly, administer the first dose of semaglutide (WEGOVY) 7 days after discontinuing semaglutide (OZEMPIC).
Titration & Administration Requirements
- All other patients being started on semaglutide (WEGOVY) should be titrated according to the recommended schedule available in the prescribing information.
- Patient education must be provided.
Document 421: Weight Management Medications Clinical Recommendations
Criteria for General Weight Management & Shared Requirements
- BMI > 30 kg/m² or BMI > 27 kg/m² with obesity-related conditions
- Must be prescribed in conjunction with a comprehensive lifestyle intervention (CLI)
- Clinically meaningful weight loss is generally considered approximately a 5% reduction from baseline body weight
- WMMs should be viewed as chronic therapy; discontinuation is commonly associated with weight regain
- Shared decision-making required considering efficacy, adverse effects, contraindications and warnings, comorbidities, patient preferences, cost, and applicable CFU
- Review current treatment regimen for medications that may contribute to weight gain and consider alternative therapy when appropriate
Criteria for Comprehensive Lifestyle Intervention (CLI) Participation
- Documentation of participation in CLI within the past year on at least one occasion is required for eligibility
- CLI must target all three aspects of weight management: diet, physical activity, and behavioral changes
- Self-management tools without clinician contact do not meet the definition of CLI
- Routine lifestyle education/coaching without a standardized curriculum delivered over a series of sessions does not meet the definition of CLI
- Programs targeting only one or two aspects of weight management do not meet the definition of CLI
Criteria for Naltrexone/Bupropion
- VANF Status: PA-F (CFU)
- Route/Frequency: Oral; twice daily
- Avoid/Contraindications: Pregnancy, Lactation, Seizure disorder, Eating disorders, Uncontrolled hypertension, Chronic opioid use or acute opioid withdrawal, MAOI use within 14 days
- Post-Marketing Considerations: Type 2 diabetes
- Monitoring & Safety: Monitor blood pressure, heart rate, and mood; Precautions include suicidal behavior and ideation [Boxed Warning]
- Common ADRs: Nausea, constipation, acute headache, vomiting, dizziness, insomnia, dry mouth, diarrhea, anxiety
Criteria for Orlistat
- VANF Status: PA-F (CFU)
- Route/Frequency: Oral; three times daily with meals
- Avoid/Contraindications: Pregnancy, Lactation, Chronic malabsorption syndrome, Cholestasis
- Post-Marketing Considerations: Prediabetes, Type 2 diabetes, BP lowering
- Monitoring & Safety: Monitor hepatotoxicity; Precautions include fat-soluble vitamin deficiency and oxalate nephropathy
- Common ADRs: Oily spotting/stools, fecal urgency, flatulence
Criteria for Phentermine/Topiramate
- VANF Status: PA-F (CFU)
- Route/Frequency: Oral; once daily
- Avoid/Contraindications: Pregnancy, Lactation, Glaucoma, Hyperthyroidism, MAOI use within 14 days
- Post-Marketing Considerations: Prediabetes, Type 2 diabetes, BP lowering
- Monitoring & Safety: Monitor heart rate, blood pressure, and mood changes; Precautions include fetal toxicity (REMS), nephrolithiasis risk, and seizure risk with abrupt discontinuation
- Common ADRs: Paraesthesias, dysgeusia, insomnia, constipation, dry mouth
Criteria for Semaglutide (Injection and Oral)
- VANF Status: NF (CFU)
- Route/Frequency: Subcutaneous; once weekly (injection) / Oral; once daily on an empty stomach with up to 4 ounces of water (tablet); Eating, drinking, and taking other medications must be avoided for 30 minutes (oral)
- Avoid/Contraindications: Pregnancy, Lactation
- Post-Marketing Considerations: Prediabetes
- Monitoring & Safety: Monitor risk of worsening diabetic retinopathy in patients with T2DM; Precautions include gallbladder disease and pancreatitis; Avoid concurrent use of a DPP-4 inhibitor due to lack of efficacy
- Common ADRs: GI adverse effects (nausea, diarrhea, constipation, vomiting, abdominal pain), dyspepsia
- FDA-Approved Indications: MASH, Reduction of MACE, Type 2 diabetes (under different brand and doses)
- Post-Marketing Evidence: Prediabetes, HFpEF, Osteoarthritis
Criteria for Liraglutide
- VANF Status: NF (CFU)
- Route/Frequency: Subcutaneous; once daily
- Avoid/Contraindications: Pregnancy, Lactation
- Post-Marketing Considerations: Prediabetes
- Monitoring & Safety: Precautions include gallbladder disease and pancreatitis
- Common ADRs: GI adverse effects (nausea, diarrhea, constipation, vomiting, abdominal pain), dyspepsia
- FDA-Approved Indications: Type 2 diabetes (under different doses), Reduction of MACE (in T2D)
- Post-Marketing Evidence: Prediabetes, Reduction of MASH
Criteria for Tirzepatide
- VANF Status: NF (CFU)
- Route/Frequency: Subcutaneous; once weekly
- Avoid/Contraindications: Pregnancy, Lactation
- Post-Marketing Considerations: Prediabetes, BP lowering
- Monitoring & Safety: Monitor risk of worsening diabetic retinopathy in patients with T2DM; Precautions include gallbladder disease and pancreatitis; Avoid concurrent use of a DPP-4 inhibitor due to lack of efficacy
- FDA-Approved Indications: MASH, Reduction of MACE, Type 2 diabetes (under different brand)
- Post-Marketing Evidence: Prediabetes, BP lowering, HFpEF, Osteoarthritis
Document 805: MON Semaglutide WEGOVY in Metabolic Dysfunction associated Steatohepatitis Monograph Jan 2026
Indication & Patient Population
- Treatment of noncirrhotic metabolic dysfunction-associated steatohepatitis (MASH) with moderate to advanced liver fibrosis (consistent with stages F2 to F3) in adults
- Applicable to overweight or obese patients and lean patients with biopsy-confirmed MASH with stage 2 or 3 liver fibrosis
Dosing & Administration
- Initial Dosage: 0.25 mg SC once weekly for 4 weeks
- Escalation (once weekly SC): 0.5 mg on Weeks 5–8, 1 mg on Weeks 9–12, and 1.7 mg on Weeks 13–16
- Maintenance: 2.4 mg from Week 17 onward; if not tolerated, decrease to 1.7 mg once weekly; consider reescalation to 2.4 mg
Pretreatment Requirements
- Check baseline glucose in patients with type 2 diabetes (T2D) due to hypoglycemia risk
- Consider dosage reduction of concomitant insulin or insulin secretagogues (e.g., sulfonylureas) prior to initiation
Monitoring & Safety Considerations
- Monitor glucose in patients with T2D
- Monitor renal function in patients with adverse reactions (e.g., vomiting, diarrhea) that could lead to volume depletion
- Monitor for diabetic retinopathy complications in patients with history of diabetic retinopathy
- Monitor for increased heart rate
- Monitor for depression or suicidal thoughts
Contraindications & Warnings
- Contraindicated in personal or family history of medullary thyroid carcinoma (MTC) or Multiple Endocrine Neoplasia syndrome type 2 (MEN 2)
- Contraindicated in pregnancy; may cause fetal harm. Discontinue at least 2 months before a planned pregnancy
- Lactation: Likely present in human milk; weigh risks vs benefits
- Warnings include: Thyroid C-cell tumors, acute pancreatitis, acute gallbladder disease, hypoglycemia (with insulin/secretagogue), acute kidney injury, severe gastrointestinal adverse reactions, hypersensitivity reactions, diabetic retinopathy complications (in T2D), increased heart rate, suicidal behavior and ideation, pulmonary aspiration during general anesthesia or deep sedation
Lifestyle & Adjunctive Therapy Requirements
- Must be used in patients with a documented plan on addressing and monitoring appropriate lifestyle interventions
- Should be combined with a reduced calorie diet and increased physical activity
- Comprehensive lifestyle intervention (CLI) should aim for 5–10% weight loss after six months; treatment should continue until long-term weight loss goals are achieved or modified if short/intermediate-term goals are not met
Document 824: Semaglutide WEGOVY in Metabolic Dysfunction Associated Steatohepatitis Criteria Jan 2026
Exclusion Criteria
- Child-Pugh score ≥ 7 (bilirubin adjustable for Gilbert syndrome; score adjusted for patients taking anticoagulants)
- Decompensated liver cirrhosis manifested by complications (e.g., noncardiac ascites, variceal hemorrhage, hepatic encephalopathy, spontaneous bacterial peritonitis)
- Most recent assessment showing FibroScan LSM > 18 kPa or VCTE consistent with cirrhosis, MRE > 5.0 kPa, FIB-4 > 2.67 (unless LSM < 18 kPa), or liver biopsy indicating cirrhosis (METAVIR stage F4)
- Hepatocellular carcinoma currently not actively managed by hepatology or multidisciplinary team
- Uncontrolled liver disease associated with condition other than metabolic dysfunction (e.g., biliary obstruction, viral hepatitis, autoimmune hepatitis, hereditary liver disease, drug-induced liver disease)
- Heavy alcohol ingestion > 3 consecutive months within previous 1 year (≥4 drinks/day for men, ≥3 drinks/day for women)
- Personal or first-degree family history of medullary thyroid carcinoma or multiple endocrine neoplasia syndrome type 2
- Severe gastrointestinal dysmotility, including gastroparesis
- History or presence of pancreatitis (except when cause is known and no longer presents a risk)
- Type 1 diabetes (unless followed by a diabetes specialist under careful supervision)
- Known PDR, severe NPDR, clinically significant ME, or DME unless risks/benefits discussed with patient, documented in EHR with monitoring plans/follow-up with informed eye specialist at initiation
- Known pregnancy
- Lactating
Core Inclusion Criteria
- Initiated by a VA/VA Community Care gastroenterologist/hepatologist or locally designated expert
- Documented plan addressing and monitoring appropriate lifestyle interventions
- Documented plan to change medications that can cause or exacerbate steatohepatitis to alternative agents as applicable and clinically appropriate
Additional Inclusion Criteria (Select if Applicable)
- Overweight/obese patients: Documented MASH with moderate to advanced fibrosis consistent with stage F2 or F3 diagnosed in past 6 months on noninvasive tests (or past 36 months on liver biopsy)
- Lean patients with suspected MASH: Documented MASH with moderate to advanced fibrosis consistent with stage F2 or F3 diagnosed on liver biopsy in past 36 months (exclude non-MASH liver diagnoses)
- Patients on semaglutide for MASH only: Initiated by a VA/VA Community Care gastroenterologist/hepatologist OR locally designated expert in MASH management
- Females who can become pregnant: Pregnancy excluded prior to receiving semaglutide; patient counseled on contraceptives and potential risks vs benefits if pregnancy occurs
- Females breastfeeding/providing breastmilk: Counseling provided on potential risks vs benefits of treatment
Monitoring, Lifestyle & Special Population Requirements
- FIB-4 should be used with caution in patients aged > 65 years due to lower reliability
- Diabetic eye exam results required on file within past 12 months (or 24 months if no evidence of retinopathy); planned follow-up with eye provider for history of diabetic retinopathy; ophthalmology consult if concerns arise
- Weight loss targets: ≥5% improves hepatic steatosis, ≥7% improves liver inflammation/resolves MASH, ≥10% improves/stabilizes hepatic fibrosis; for normal-weight/lean MASLD (BMI <25 kg/m² non-Asians or <23 kg/m² Asians), moderate weight loss 3%–5% can improve liver histology
- Weight loss rate recommendation: slow rate such as 5% within 6 months and cumulative 10% or more within 18 months
- Noninvasive diagnostic tests for MASH F2–F3 fibrosis include ELF score 9.2–10.5, LSM 8.0–18.0 kPa, and MRE 3.1–4.4 kPa
- Patients currently on semaglutide for another indication (e.g., diabetes or obesity) diagnosed with cirrhosis or portal hypertension may continue therapy; patients with compensated cirrhosis may continue if LSM < 18 kPa, ELF < 10.5, or platelets > 130
- Medications implicated in development/exacerbation of steatohepatitis/MASLD/MASH include amiodarone, androgenic steroids, atypical antipsychotics (e.g., clozapine, olanzapine), estrogens, glucocorticoids, irinotecan, methotrexate, nucleoside reverse transcriptase inhibitors, SSRIs, tamoxifen, valproic acid
Source Documents
Document 233: Semaglutide WEGOVY for weight management CFU
Document 410: Semaglutide WEGOVY Conversion Guidance
Document 421: Weight Management Medications Clinical Recommendations
Document 805: MON Semaglutide WEGOVY in Metabolic Dysfunction associated Steatohepatitis Monograph Jan 2026
Document 824: Semaglutide WEGOVY in Metabolic Dysfunction Associated Steatohepatitis Criteria Jan 2026