SEMAGLUTIDE INJ,SOLN
Clinical Criteria Summary
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Exclusion Criteria
- Known pregnancy
- Lactating
- Type 1 diabetes (exception: may be considered under careful supervision if followed by a diabetes/weight management specialist)
- Personal or family history of medullary thyroid carcinoma or Multiple Endocrine Neoplasia syndrome type 2
- Severe gastrointestinal dysmotility, including gastroparesis
- History of pancreatitis (exception: does not apply when the cause is known and no longer presents a risk)
- Known PDR, severe NPDR, clinically significant ME, or DME unless risks/benefits discussed with patient, documented in EHR with monitoring plans/follow-up with an eye specialist informed at initiation
Inclusion Criteria
- Documented participation in a comprehensive lifestyle intervention (CLI) targeting diet, physical activity, and behavioral changes
- BMI ≥ 30 kg/m² with at least one weight-related comorbidity (e.g., hypertension, type 2 diabetes, dyslipidemia, metabolic syndrome, obstructive sleep apnea, osteoarthritis, metabolic dysfunction-associated steatotic liver disease)
- Indicated to reduce a secondary cardiovascular event in patients 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 atherosclerotic disease) who have overweight or obesity
Additional Inclusion Criteria
- For females who can become pregnant: Pregnancy must be excluded prior to receiving semaglutide (WEGOVY); contraceptive counseling on potential risks vs. benefits if pregnancy occurs is required
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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.
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Indications & Eligibility
- For chronic weight management in conjunction with comprehensive lifestyle intervention
- Offered to patients with a body mass index (BMI) > 30 kg/m² and to those with a BMI > 27 kg/m² who also have obesity-associated conditions
- Formulary status: VA National Formulary (VANF) with Prior Authorization at the Facility level (PA-F) with Criteria for Use (CFU); not a controlled substance
Inclusion Criteria
- Documented participation in a comprehensive lifestyle intervention targeting diet, physical activity, and behavioral changes within the past year
- Participation may include MOVE! programs, remote patient monitoring home telehealth (TeleMOVE!/L2), clinically supported web/mobile applications with clinical contact, or non-VA programs meeting the operational definition
Exclusion Criteria & Contraindications
- Pregnancy
- Breastfeeding
- Uncontrolled hypertension
- Seizure disorder
- Bulimia or anorexia nervosa
- Chronic opioid use or acute opioid withdrawal
- Monoamine oxidase inhibitor (MAOI) use during or within 14 days
- Abrupt discontinuation of alcohol, benzodiazepines, barbiturates, or antiepileptic drugs
Efficacy & Monitoring Goals
- Initial weight loss goal: ≥5% weight loss by 12 weeks
- Discontinue if the 5% weight loss goal is not achieved at 12 weeks, as clinically meaningful reduction is unlikely with continued treatment
- Weight maintenance goals for continued therapy: Maintenance of ≥67% initial weight loss, >5% loss from baseline weight, or continued weight loss
- Discontinue if sufficient weight loss is not achieved within the first 3 months on a maximally tolerated dose or if significant weight gain/regain occurs after initial loss
Comorbidity Considerations
- Hypertension: Contraindicated in uncontrolled hypertension; may increase blood pressure or cause hypertension
- Cardiac/Cerebrovascular Disease: Monitor heart rate or blood pressure per usual practice; discontinue if sustained. Unknown impact on listed comorbidities as several conditions were excluded from clinical trials
- Diabetes: Improved glycemic parameters in diabetes mellitus
- Mental Health Conditions/Suicidality: Boxed warning for suicidal behavior and ideation; monitor patients especially during initial months and with dose changes. Post-marketing meta-analyses support no increased risk in suicidal ideation/behavior
- Seizure Disorder: Contraindicated; seizures may occur, with increased risk from factors that decrease seizure threshold
- Nephrolithiasis: May increase urinary oxalate and risk of oxalate nephrolithiasis; use caution in renal impairment or history of hyperoxaluria/calcium oxalate stones; discontinue if oxalate nephropathy develops
- Glaucoma: Pupillary dilation may precipitate an attack in those at risk for narrow-angle glaucoma
Safety Warnings & Precautions
- Boxed Warning: Suicidal behavior and ideation
- Neuropsychiatric adverse events and suicide risk (noted in smoking cessation context)
- Increased blood pressure and heart rate
- Hepatotoxicity; adjust dose in hepatic impairment, not recommended in severe hepatic impairment
- Activation of mania
- Angle-closure glaucoma
- Hypoglycemia with use of antidiabetic medications
- Adjust dose in moderate to severe renal impairment; avoid in end-stage renal disease (ESRD)
- Vulnerability to opioid overdose and precipitated opioid withdrawal
Prescribing & Refill Requirements
- Initial refill after 12 to 24 weeks: Patient must continue participation in a comprehensive lifestyle intervention or have completed one with a follow-up visit for ongoing education/support
- Refills every 6 months: Maintenance of ≥67% initial weight loss, >5% loss from baseline, or continued weight loss is the reasonable goal; no specific documentation requirement for CLI participation at this stage, though ongoing participation remains important for maintenance
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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
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Exclusion Criteria
- Child-Pugh score ≥ 7 (bilirubin adjustable for Gilbert syndrome; score adjusted for patients taking anticoagulants)
- Decompensated liver cirrhosis manifested by complications (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); 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 the previous 1 year (≥4 drinks/day for men, ≥3 drinks/day for women; defined by specific volumes/ABV)
- 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 for careful supervision)
- Known PDR, severe NPDR, clinically significant ME, or DME (unless risks/benefits discussed, documented in EHR with monitoring plans, and eye specialist informed at initiation)
- Known pregnancy
- Lactating
Inclusion Criteria
- Initiated by a VA/VA Community Care gastroenterologist/hepatologist or locally designated expert
- Documented plan for addressing and monitoring appropriate lifestyle interventions
- Documented plan to change medications that cause or exacerbate steatohepatitis to alternative agents as applicable and clinically appropriate
Diagnostic & Fibrosis Parameters
- Overweight/obese patients: Documented MASH with moderate to advanced fibrosis (stage F2 or F3) diagnosed within 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 (stage F2 or F3) diagnosed on liver biopsy within past 36 months (exclude non-MASH diagnoses)
- Noninvasive test thresholds for MASH F2–F3: ELF score 9.2–10.5; LSM 8.0–18.0 kPa; MRE 3.1–4.4 kPa
- Weight loss targets: Slow rate (5% within 6 months, cumulative ≥10% within 18 months); ≥5% improves hepatic steatosis, ≥7% improves liver inflammation/resolves MASH, ≥10% improves/stabilizes hepatic fibrosis; lean MASLD may improve histology with 3%–5% weight loss
- FIB-4 should be used with caution in patients >65 years due to lower reliability
Specialist Initiation & Monitoring Requirements
- Patients on semaglutide for MASH only must be initiated by a VA/VA Community Care gastroenterologist/hepatologist OR a locally designated expert in MASH management
- 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 obtained for any concerns related to use
Pregnancy & Lactation Counseling
- Females who can become pregnant: Pregnancy must be excluded prior to receiving semaglutide; patient counseled on contraceptives and risks/benefits if pregnancy occurs
- Females breastfeeding/providing breastmilk: Counseling provided on potential risks vs benefits of treatment
Other
- Other justification field available for clinical documentation