SEMAGLUTIDE TAB
Clinical Criteria Summary
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 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