Xenical Vs. Wegovy: Drug Comparison

Xenical^® (orlistat) is a prescription medication used for weight management by inhibiting the enzyme lipase, which reduces the absorption of dietary fats in the intestines, thereby helping with weight loss. Its FDA-approved indication is for obesity management, including weight loss and weight maintenance, in conjunction with a reduced-calorie diet. Xenical is available in capsule form and is typically taken three times daily with meals containing fat. Common side effects include gastrointestinal issues such as oily stools, flatulence, and frequent bowel movements, especially after consuming high-fat meals. Xenical can affect the absorption of fat-soluble vitamins, and patients are advised to take a multivitamin supplement to avoid deficiencies.

Wegovy^® (semaglutide) is an injectable medication approved for chronic weight management in adults with obesity or overweight with at least one weight-related condition, such as hypertension, type 2 diabetes, or high cholesterol. It works by mimicking the hormone glucagon-like peptide-1 (GLP-1), which regulates appetite and food intake, leading to reduced calorie consumption and significant weight loss. Wegovy is administered once weekly and is intended to be used in conjunction with a reduced-calorie diet and increased physical activity. Common side effects include nausea, diarrhea, vomiting, and constipation. It should be used with caution in patients with a history of pancreatitis and is not recommended for use in pregnant or breastfeeding individuals​.

Reversible inhibitor of gastrointestinal lipases

Glucagon-like peptide-1 (GLP-1) receptor agonist

Xenical (orlistat) is indicated:

• For obesity management including weight loss and weight maintenance when used in conjunction with a reduced-calorie diet

• To reduce the risk for weight regain after prior weight loss

Wegovy (semaglutide) is indicated in combination with a reduced calorie diet and increased physical activity:

• To reduce the risk of major adverse cardiovascular events (cardiovascular death, non-fatal myocardial infarction, or non-fatal stroke) in adults with established cardiovascular disease and either obesity or overweight

• To reduce excess body weight and maintain weight reduction long term in:

  • Adults and pediatric patients aged 12 years and older with obesity

  • Adults with overweight in the presence of at least one weight-related comorbid condition

• Typically taken three times daily

• Comes in 120 mg capsules

• Typically taken as an injection once weekly

• Comes in single-dose pens that deliver 0.25 mg, 0.5 mg, 1 mg, 1.7 mg, or 2.4 mg per injection

Most common treatment emergent adverse reactions (≥5% and at least twice that of placebo) include:

• Oily spotting

• Flatus with discharge

• Fecal urgency

• Fatty/Oily stool

• Oily evacuation

• Increased defecation

• Fecal incontinence

Most common adverse reactions (incidence ≥5%) in adults or pediatric patients aged 12 years and older are:

• Nausea

• Diarrhea

• Vomiting

• Constipation

• Abdominal pain

• Headache

• Fatigue

• Indigestion

• Dizziness

• Abdominal distension

• Belching

• Low blood sugar in patients with type 2 diabetes

• Flatulence

• Inflammation of the digestive system

• Gastroesophageal reflux disease (heartburn)

• Inflammation of the nasal cavities and back of the throat

• Pregnancy

• Chronic malabsorption syndrome

• Cholestasis

• Known hypersensitivity to Xenical or to any component of this product

• Drug interactions: Cyclosporine, fat-soluble vitamin supplements and analogues, levothyroxine, warfarin, amiodarone, antiepileptic drugs, antiretroviral drugs

• Personal or family history of medullary thyroid carcinoma or in patients with multiple endocrine neoplasia syndrome type 2

• Known hypersensitivity to semaglutide or any of the excipients in Wegovy

• Drug interactions: Wegovy delays gastric emptying. May impact absorption of concomitantly administered oral medications

• Xenical has drug interactions and can decrease vitamin absorption

• Take a multivitamin supplement that contains fat-soluble vitamins to ensure adequate nutrition

• Rare cases of severe liver injury with hepatocellular necrosis or acute hepatic failure have been reported

• Patients may develop oxalate nephrolithiasis and oxalate nephropathy following treatment with Xenical

• Substantial weight loss can increase the risk of cholelithiasis

• Exclude organic causes of obesity (e.g., hypothyroidism) before prescribing Xenical

• Gastrointestinal events may increase when Xenical is taken with a diet high in fat (>30% total daily calories from fat)

• Breastfeeding: Caution should be exercised when administered to a nursing woman

• Acute pancreatitis

• Acute gallbladder disease

• Low blood sugar: Concomitant use with insulin or an insulin secretagogue may increase the risk of low blood sugar, including severe low blood sugar

• Acute kidney injury

• Hypersensitivity reactions

• Diabetic retinopathy complications in patients with type 2 diabetes

• Heart rate increase

• Suicidal behavior and ideation

• Pregnancy: May cause fetal harm. When pregnancy is recognized, discontinue Wegovy

• Females and males of reproductive potential: Discontinue Wegovy at least 2 months before a planned pregnancy because of the long half-life of semaglutide

WARNING: RISK OF THYROID C-CELL TUMORS

In rodents, semaglutide causes thyroid C-cell tumors at clinically relevant exposures. It is unknown whether Wegovy causes thyroid C-cell tumors, including medullary thyroid carcinoma (MTC), in humans as the human relevance of semaglutide-induced rodent thyroid C-cell tumors has not been determined.

Wegovy is contraindicated in patients with a personal or family history of MTC or in patients with multiple endocrine neoplasia syndrome type 2 (MEN 2). Counsel patients regarding the potential risk of MTC and symptoms of thyroid tumors.

*This information is from the label for brand name Xenical^®. See the Full Prescribing Information for more complete information. Orlistat, the active ingredient in Xenical, may also be the active ingredient in other medications, and this information may not be accurate for all medications that include the active ingredient orlistat.

*This information is from the label for brand name Wegovy^®. See the Full Prescribing Information for more complete information. Semaglutide, the active ingredient in Wegovy, may also be the active ingredient in other medications, and this information may not be accurate for all medications that include the active ingredient semaglutide.