What about other medications like semaglutide (GLP-1 receptor agonist) for weight loss?

Semaglutide (GLP-1 Receptor Agonist) for Weight Loss

Semaglutide 2.4 mg weekly is highly effective for weight loss and should be strongly considered for patients with obesity (BMI ≥30) or overweight (BMI ≥27 with weight-related comorbidities), achieving superior weight loss of 14.9% at 68 weeks compared to other anti-obesity medications. 1

Mechanism of Action and Clinical Efficacy

Semaglutide acts as a GLP-1 receptor agonist that suppresses appetite through hypothalamic action, delays gastric emptying, increases glucose-dependent insulin release, decreases glucagon secretion, and promotes pancreatic β-cell growth. 1, 2 The glucose-dependent mechanism means minimal hypoglycemia risk when used as monotherapy. 1

Weight loss outcomes are substantial:

• Mean weight loss of 14.9% at 68 weeks in patients without diabetes 1, 3
• 64.9% of patients achieve ≥10% total body weight loss 1
• Weight loss extends to 15.2% at 104 weeks (2 years) in long-term studies 3
• Superior to liraglutide 3.0 mg (which achieves 5.24-6.1% weight loss) 1, 4

Weight loss is greater in non-diabetic patients (6.1-17.4%) compared to those with type 2 diabetes (4-6.2%). 1

Cardiovascular Benefits Beyond Weight Loss

Semaglutide provides proven cardiovascular protection, particularly important for patients with established cardiovascular disease. 1 The SELECT trial demonstrated a 20% reduction in the composite incidence of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke (HR 0.80) in patients with cardiovascular disease and BMI ≥27. 1 The SUSTAIN-6 trial showed a 26% reduction in major adverse cardiovascular events (HR 0.74,95% CI 0.58-0.95). 1

Additional cardiometabolic benefits include improved myocardial substrate utilization, anti-inflammatory and anti-atherosclerotic effects, reduced myocardial ischemia injury, lower systemic and pulmonary vascular resistance, and improved lipid profiles. 1

Dosing and Administration

Start semaglutide at 0.25 mg weekly and titrate gradually over 16 weeks to the maintenance dose of 2.4 mg weekly: 1

• Weeks 1-4: 0.25 mg weekly
• Weeks 5-8: 0.5 mg weekly
• Weeks 9-12: 1.0 mg weekly
• Weeks 13-16: 1.7 mg weekly
• Week 17 onward: 2.4 mg weekly (maintenance)

Administer as subcutaneous injection once weekly in the abdomen, thigh, or upper arm. 2 Slow titration minimizes gastrointestinal side effects. 1

If 2 consecutive doses are missed, resume at the same dose if previously tolerated; if 3 or more doses are missed, consider restarting the titration schedule. 1

Safety Profile and Adverse Effects

Gastrointestinal effects are the most common adverse events, including nausea, vomiting, diarrhea, and constipation, which are typically mild-to-moderate and decrease over time. 1, 3 The gradual dose escalation schedule specifically addresses this concern. 1

Serious but rare risks include: 1

• Pancreatitis (monitor for persistent severe abdominal pain)
• Gallbladder disease (cholelithiasis, cholecystitis)
• Acute kidney injury

Semaglutide shows a 38% higher rate of serious adverse events compared to placebo (95% CI 1.10-1.73), though treatment discontinuation rates are only 34 more per 1000 patients compared to placebo. 1

Absolute Contraindications

Semaglutide is contraindicated in patients with: 1, 2

• Personal or family history of medullary thyroid cancer
• Multiple endocrine neoplasia syndrome type 2

These contraindications are based on animal studies showing thyroid C-cell tumors. 2

Critical Clinical Considerations

Long-term use is necessary for sustained benefit. After cessation of semaglutide, significant weight regain occurs (11.6% of lost weight regained after 52 weeks). 1 Patients must understand this is likely a lifelong medication when used for obesity management. 1

Combine with lifestyle modifications: Semaglutide must be used as an adjunct to reduced-calorie diet and increased physical activity. 1, 5 Resistance training should be emphasized to preserve lean body mass. 1

Monitor blood pressure closely as weight loss progresses, since antihypertensive medication requirements may decrease. 1

Perioperative risk: Retained gastric contents are documented even after extended fasting periods, creating aspiration risk during anesthesia. Cases have been reported in patients who stopped semaglutide 4-6 days before surgery, with increased residual gastric content found in 24.2% of semaglutide users versus 5.1% of controls. 1 Consider extended discontinuation before elective surgery.

Special Populations

No dose adjustment is required for: 2

• Renal impairment (including end-stage renal disease)
• Hepatic impairment (mild, moderate, or severe)
• Age, sex, race, or ethnicity

For patients with type 2 diabetes and obesity, semaglutide offers dual benefits of improved glycemic control (HbA1c reduction of 1.48%) and weight loss. 1 Do not use with other GLP-1 receptor agonists or DPP-4 inhibitors. 1

Comparison with Other Anti-Obesity Medications

Semaglutide 2.4 mg demonstrates superior efficacy compared to other approved anti-obesity medications, with the American Gastroenterological Association suggesting it may be prioritized for most patients given the magnitude of net benefit. 1 It is currently the only once-weekly weight loss medication. 5

The South and Southeast Asia consensus notes that semaglutide 2.4 mg is approved for obesity treatment in the United States and Europe but not yet in Asia, though semaglutide is approved for type 2 diabetes in that region and is associated with significant weight loss. 6

Monitoring Requirements

Assess patients at least every 3 months for: 1

• Weight loss progress
• Cardiovascular risk factors
• Medication adherence
• Signs of pancreatitis or gallbladder disease
• Blood pressure changes
• Nutritional status

Evaluate efficacy at 12-16 weeks on maximum tolerated dose. If inadequate response, consider intensifying treatment with additional approaches such as metabolic surgery or additional pharmacologic agents. 1