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 Phentermine/Topiramate
- Inclusion/Exclusion Criteria: Excluded in pregnancy, hyperthyroidism, and MAOI use during or within 14 days. Requires documented participation in a comprehensive lifestyle intervention targeting diet, physical activity, and behavioral changes within the past year.
- Efficacy & Maintenance Goals: Initial: If 3% weight loss not achieved at 12 weeks on 7.5 mg/46 mg, increase dose per prescribing information. If 5% loss of baseline body weight not achieved at 12 weeks on 15 mg/92 mg, taper to discontinue. Maintenance: Maintain ≥67% initial weight loss or >5% loss from baseline weight or continued weight loss; ongoing participation in comprehensive lifestyle intervention required.
- Comorbidity Considerations:
- Hypertension: ↓ BP in HTN; Warning/Precaution for risk of hypotension with antihypertensive medications.
- Cardiac/Cerebrovascular Disease: Warning/Precaution for ↑ HR, monitor (especially in cardiac or cerebrovascular disease); ↓ or DC if sustained. Not recommended or studied in recent or unstable disease.
- Diabetes Mellitus: Improved glycemic parameters in DM.
- Mental Health Conditions/Suicidality: Dose-related ↑ depression, anxiety, adverse events; Warning/Precaution for mood and sleep disorders, cognitive impairment.
- Seizure Disorder: Warning/Precaution; Abrupt DC may cause seizures (regardless of history); ↑ risk for seizures; taper if DC.
- Nephrolithiasis: Warning/Precaution; Risk may be ↑ with ketogenic diet or ↑ urinary oxalate and concomitant carbonic anhydrase inhibitors; may ↓ risk with ↑ fluid intake.
- Glaucoma: Contraindication; Warning/Precaution for acute myopia and secondary angle closure glaucoma; DC if acute onset ↓ visual acuity or ocular pain.
- Contraindications & Warnings/Precautions: Fetal toxicity (REMS), ↑ HR, suicidal behavior and ideation, acute myopia and secondary angle closure glaucoma, metabolic acidosis, hypokalemia, adjust dose per CrCl (avoid in ESRD), nephrolithiasis, adjust dose in moderate hepatic impairment, hypoglycemia with antidiabetic medications, oligohidrosis and hyperthermia, serious skin reactions, avoid abrupt withdrawal due to potential for seizures, contains phentermine (potential for abuse), interference with absorption of fat-soluble vitamins, cyclosporine, warfarin, amiodarone, thyroid hormone, antiepileptic drugs, and antiretroviral drugs.
Criteria for Orlistat
- Inclusion/Exclusion Criteria: Excluded in pregnancy, chronic malabsorption syndrome, and cholestasis. Requires documented participation in a comprehensive lifestyle intervention targeting diet, physical activity, and behavioral changes within the past year.
- Efficacy & Maintenance Goals: Initial: 3% weight loss at 12 weeks. Maintenance: Maintain ≥67% initial weight loss or >5% loss from baseline weight or continued weight loss; ongoing participation in comprehensive lifestyle intervention required.
- Comorbidity Considerations:
- Hypertension: ↓ BP in HTN.
- Cardiac/Cerebrovascular Disease: Unknown impact on listed comorbidity as several conditions excluded from clinical trials.
- Diabetes Mellitus: Improved glycemic parameters in DM; ↓ risk of DM.
- Mental Health Conditions/Suicidality: Boxed Warning for suicidal behavior or ideation; Warning/Precaution for neuropsychiatric adverse events and suicide risk (in smoking cessation).
- Nephrolithiasis: Warning/Precaution; ↑ urinary oxalate and risk of oxalate nephrolithiasis and oxalate nephropathy; caution in renal impairment, history hyperoxaluria or calcium oxalate stones. DC if oxalate nephropathy develops.
- Contraindications & Warnings/Precautions: Hepatotoxicity, cholelithiasis, oxalate nephrolithiasis and oxalate nephropathy with renal failure, gastrointestinal events if taken with a diet high in fat.
Criteria for Naltrexone/Bupropion
- Inclusion/Exclusion Criteria: Excluded in pregnancy, seizure disorder, bulimia or anorexia nervosa, chronic opioid use or acute opioid withdrawal, MAOI use during or within 14 days, and abrupt discontinuation of alcohol, benzodiazepines, barbiturates, antiepileptic drugs. Requires documented participation in a comprehensive lifestyle intervention targeting diet, physical activity, and behavioral changes within the past year.
- Efficacy & Maintenance Goals: Initial: 5% weight loss by 12 weeks; per prescribing information, discontinue if not achieved. Maintenance: Maintain ≥67% initial weight loss or >5% loss from baseline weight or continued weight loss; ongoing participation in comprehensive lifestyle intervention required.
- Comorbidity Considerations:
- Hypertension: Contraindication in Uncontrolled HTN; Warning/Precaution May ↑ BP/cause HTN.
- Cardiac/Cerebrovascular Disease: Warning/Precaution ↑ HR or BP, monitor per usual practice; DC if sustained.
- Diabetes Mellitus: Improved glycemic parameters in DM.
- Mental Health Conditions/Suicidality: Boxed Warning for suicidal behavior or ideation; Warning/Precaution for mood and sleep disorders, cognitive impairment; Monitor patients especially during initial months, dose changes post-marketing; multiple post-marketing meta-analyses support no increased risk in suicidal ideation and/or behavior and FDA has issued a letter for this to be removed from prescribing information.
- Nephrolithiasis: May ↑ urinary oxalate and risk of oxalate nephropathy; caution in renal impairment.
- Contraindications & Warnings/Precautions: Suicidal behavior and ideation [Boxed Warning], neuropsychiatric adverse events and suicide risk, seizures (increased risk with factors that decrease seizure threshold), vulnerability to opioid overdose, precipitated opioid withdrawal, hepatotoxicity (adjust dose in hepatic impairment, not recommended in severe hepatic impairment), activation of mania, increased blood pressure and heart rate, hypoglycemia with use of antidiabetic medications, adjust dose in moderate to severe renal impairment (avoid in ESRD).
Criteria for Liraglutide, Semaglutide, and Tirzepatide
- Inclusion/Exclusion Criteria: Excluded in pregnancy (liraglutide only per table note), personal or family history of medullary thyroid carcinoma, or multiple endocrine neoplasia type 2 (MEN2). Requires documented participation in a comprehensive lifestyle intervention targeting diet, physical activity, and behavioral changes within the past year.
- Efficacy & Maintenance Goals:
- Liraglutide: Initial: 4% weight loss at week 16; per prescribing information, discontinue if not achieved. Maintenance: Maintain ≥67% initial weight loss or >5% loss from baseline weight or continued weight loss; ongoing participation in comprehensive lifestyle intervention required.
- Semaglutide: Initial: 5% weight loss after achieving dose titration to a maintenance dose of 2.4 mg (recommended) (approximately 20 weeks) or 1.7 mg once weekly for injection or 25 mg daily for oral tablet. Per prescribing information, if a dose is not tolerated during titration, the dose increase can be delayed for 4 weeks. Maintenance: Maintain ≥67% initial weight loss or >5% loss from baseline weight or continued weight loss; ongoing participation in comprehensive lifestyle intervention required.
- Tirzepatide: Initial: 5% weight loss after achieving dose titration to a maintenance dose of 5 mg, 10 mg, or 15 mg once weekly (titration duration ranges 4-16 weeks depending on maintenance dose). Per prescribing information, if a maintenance dose is not tolerated, a lower maintenance dose should be considered. Maintenance: Maintain ≥67% initial weight loss or >5% loss from baseline weight or continued weight loss; ongoing participation in comprehensive lifestyle intervention required.
- Comorbidity Considerations:
- Hypertension: ↓ BP in HTN reported in ADRs of semaglutide and tirzepatide.
- Cardiac/Cerebrovascular Disease: Warning/Precaution ↑ HR, monitor. Semaglutide: ↓ risk of death from CV cause, nonfatal MI, or nonfatal stroke in preexisting CV disease without diabetes. No specific precaution for listed comorbidity otherwise.
- Diabetes Mellitus: Improved glycemic parameters in DM. Avoid use of a concurrent DPP-4 inhibitor due to lack of additive efficacy. Liraglutide: ↓ risk of DM. Semaglutide and Tirzepatide: Improved glycemic parameters in preDM.
- Mental Health Conditions/Suicidality: Monitor for emergence or ↑ depressive symptoms, suicidal thoughts or behavior; recommend avoiding if history of suicide attempts or active suicidal ideation.
- Contraindications & Warnings/Precautions: Thyroid C-cell tumors (medullary carcinoma) [Boxed Warning], acute pancreatitis, acute cholelithiasis or cholecystitis, severe gastrointestinal adverse reactions (intestinal obstruction, severe constipation including fecal impaction), hypoglycemia (may need to adjust concomitant DM agents), ↑ HR, renal impairment (use with caution in existing CKD for liraglutide; acute kidney injury for semaglutide and tirzepatide), diabetic retinopathy complications (semaglutide and tirzepatide).
Shared Criteria for All Weight Management Medications
- Efficacy/Discontinuation Rule: If sufficient weight loss is not achieved within the first 3 months of a maximally tolerated dose or significant weight gain/regain after initial loss occurs, discontinue medication. A trial of a different weight management medication may be warranted provided the patient continues to adhere to comprehensive lifestyle intervention.
- Refill Requirements: Initial refill after 12 to 24 weeks requires continued participation in a comprehensive lifestyle intervention (or previously completed one within the past year with at least one follow-up visit). Refills every 6 months require no specific documentation for continued lifestyle intervention, but maintenance of ≥67% initial weight loss or >5% loss from baseline weight or continued weight loss is a reasonable goal; continued participation may be necessary to meet these goals.
- General Prescribing Considerations: Pharmacotherapy must be in conjunction with a comprehensive lifestyle intervention (diet, physical activity, behavioral changes). Weight management medications should be viewed as long-term therapy. Selection requires shared decision-making considering efficacy, side effects, cautions, warnings, and patient comorbidities. Review current treatment regimen for medications with potential for weight gain and consider alternate therapy.
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