SEMAGLUTIDE TAB
Clinical Criteria Summary
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 835: MON Oral Semaglutide WEGOVY monograph March 2026
Indications & Patient Selection Criteria
- Adults with obesity (BMI 30 kg/m²) or overweight (BMI 27 kg/m²) with at least one weight-related comorbid condition
- Adults with established cardiovascular disease and either obesity or overweight, for reduction of major adverse cardiovascular events (CV death, non-fatal myocardial infarction, or non-fatal stroke)
- VA/DoD Clinical Practice Guideline recommends use in patients with BMI ≥ 30 kg/m² and those with BMI ≥ 27 kg/m² who also have obesity-associated conditions
Dosing & Administration Requirements
- Initial dose: 1.5 mg orally once daily for 30 days
- Titration every 30 days to 4 mg, then 9 mg, then 25 mg once daily (labelled maximum dose)
- Must be taken with no more than 4 ounces of water
- Patient must wait at least 30 minutes before eating, drinking, or taking any other medications after administration
Contraindications & Safety Warnings
- Contraindicated in patients with a personal or family history of medullary thyroid carcinoma (MTC) or Multiple Endocrine Neoplasia syndrome type 2 (MEN 2)
- Contraindicated in patients with known hypersensitivity to semaglutide or its excipients
- Warnings include: acute pancreatitis, acute gallbladder disease (cholelithiasis and cholecystitis), hypoglycemia when used with insulin or insulin secretagogues, acute kidney injury due to volume depletion, severe gastrointestinal reactions, complications from diabetic retinopathy in patients with type 2 diabetes, heart rate increase, suicidal behavior and ideation, and risk of pulmonary aspiration during general anesthesia
- May cause fetal harm; discontinue when pregnancy is recognized
- Patients of reproductive potential should discontinue treatment at least 2 months prior to a planned pregnancy due to the long half-life of semaglutide
- Breastfeeding is not recommended during treatment due to potential for serious adverse reactions in infants from possible accumulation of the absorption enhancer SNAC
Monitoring & Management Considerations
- Should be used as an adjunct to a reduced-calorie diet and increased physical activity/comprehensive lifestyle intervention
- Delayed gastric emptying may impact absorption of other oral medications; consider increased clinical or laboratory monitoring for medications with a narrow therapeutic index or requiring clinical monitoring
- Not indicated for the treatment of noncirrhotic metabolic dysfunction-associated steatohepatitis (MASH)
Place in Therapy & Formulary Context
- Indicated for weight loss/maintenance and CV event risk reduction in established CV disease and overweight/obesity
- No direct comparison trials exist versus other pharmacotherapies at doses used for weight management; indirect comparisons show similar average weight loss to injected semaglutide but slightly lower odds ratios for achieving 5%, 10%, and 15% weight loss
- Selection should consider efficacy, side effects, warnings and precautions, patient comorbidities, and medication cost
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