Ozempic (Semaglutide) for Weight Loss
Ozempic (semaglutide) is highly effective for weight loss, producing a mean weight reduction of 14.9-17.4% at 68 weeks in people without diabetes, which represents the largest weight loss achieved by any FDA-approved obesity medication to date. 1, 2
FDA Approval and Dosing
Semaglutide 2.4 mg weekly is FDA-approved specifically for chronic weight management in adults with BMI ≥30 kg/m² or BMI ≥27 kg/m² with at least one weight-related comorbidity. 1
The medication must be titrated gradually: start at 0.25 mg weekly for 4 weeks, then 0.5 mg for 4 weeks, then 1.0 mg for 4 weeks, then 1.7 mg for 4 weeks, reaching the maintenance dose of 2.4 mg weekly after 16 weeks. 1
This gradual titration is essential to minimize gastrointestinal side effects. 1, 3
Weight Loss Efficacy
In the landmark STEP 1 trial, semaglutide 2.4 mg produced mean weight loss of 14.9% versus 2.4% with placebo at 68 weeks. 1, 4
86.4% of participants achieved ≥5% weight loss, 69.1% achieved ≥10% weight loss, and 50.5% achieved ≥15% weight loss (compared to 31.5%, 12.0%, and 4.9% with placebo, respectively). 4
Weight loss continues progressively over 65 weeks and can be sustained for up to 4 years with continued treatment. 5
In the SELECT trial, at 208 weeks (4 years), semaglutide maintained a mean weight reduction of 10.2% versus 1.5% with placebo. 5
Important Caveat: Weight Loss is Lower in Diabetes
Weight loss is significantly lower in individuals with type 2 diabetes (4-6.2%) compared to those without diabetes (6.1-17.4%). 1, 3
In STEP 2 (patients with type 2 diabetes), mean weight loss was only 9.6% with semaglutide 2.4 mg versus 3.4% with placebo at 68 weeks. 2
Cardiovascular Benefits Beyond Weight Loss
The SELECT study demonstrated that semaglutide 2.4 mg reduced the composite incidence of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke by 20% (HR 0.80) in patients with cardiovascular disease and BMI ≥27. 1
These cardiovascular benefits represent a major advantage over other weight loss medications. 1
Critical Requirement: Lifelong Use
After cessation of semaglutide, significant weight regain occurs—11.6% of lost weight is regained after 52 weeks of stopping treatment. 1
Patients must understand that semaglutide needs to be used lifelong in conjunction with lifestyle modifications (hypocaloric diet with 500-kcal daily deficit and 150 minutes of physical activity per week). 1, 3
Safety Profile and Side Effects
The most common adverse effects are gastrointestinal: nausea, vomiting, diarrhea, and constipation, which are typically transient and mild-to-moderate. 1, 3, 4
Treatment discontinuation due to gastrointestinal events occurs in approximately 4.5% of patients. 4
Semaglutide is associated with a 38% higher risk of serious adverse events compared to placebo, though the SELECT trial showed lower rates of serious adverse events overall with semaglutide. 1, 5
There is an increased risk of pancreatitis and gallbladder disease. 1, 3
Absolute Contraindications
Semaglutide is contraindicated in patients with personal or family history of medullary thyroid cancer or multiple endocrine neoplasia syndrome type 2 based on animal studies showing thyroid C-cell tumors. 1, 6
Use with caution in patients with history of pancreatitis. 1
Perioperative Considerations
GLP-1 receptor agonists may be associated with increased risk of pulmonary aspiration under anesthesia, even with extended fasting periods. 1
Consider holding semaglutide before elective surgery based on institutional protocols.
Practical Implementation
Semaglutide should not be used with other GLP-1 receptor agonists or DPP-4 inhibitors. 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
Resistance training should be incorporated to preserve lean body mass during weight loss. 1
Monitor for gastrointestinal adverse effects particularly during dose escalation. 3
Monitor blood pressure as weight loss progresses, as antihypertensive medication requirements may decrease. 1