What do well-established trials tell about Ozempic (semaglutide) in reducing weight in obese individuals?

Efficacy of Semaglutide (Ozempic) for Weight Reduction in Obesity

Semaglutide 2.4 mg once weekly produces substantial weight loss of 14.9-16.0% at 68 weeks in individuals with obesity, with 69-79% of patients achieving ≥10% weight loss and 51-64% achieving ≥15% weight loss. 1, 2

Weight Loss Outcomes with Semaglutide

Short-Term Results (68 weeks)

• The Semaglutide Treatment Effect in People with obesity (STEP) clinical trial program demonstrated that semaglutide 2.4 mg weekly produced mean weight losses of 14.9-17.4% in individuals with overweight or obesity without type 2 diabetes 1
• Specific weight loss outcomes from STEP 1 trial:
  • 14.9% mean weight loss with semaglutide vs. 2.4% with placebo
  • 86.4% of participants achieved ≥5% weight loss (vs. 31.5% with placebo)
  • 69.1% achieved ≥10% weight loss (vs. 12.0% with placebo)
  • 50.5% achieved ≥15% weight loss (vs. 4.9% with placebo) 2

Long-Term Results (104 weeks)

• The STEP 5 trial demonstrated sustained weight loss over 2 years:
  • 15.2% mean weight loss with semaglutide vs. 2.6% with placebo
  • 77.1% of participants achieved ≥5% weight loss (vs. 34.4% with placebo) 3
• This demonstrates the durability of weight loss with continued semaglutide treatment

Special Populations

• In patients with type 2 diabetes and obesity (STEP 2), mean weight loss was 9.6% with semaglutide 2.4 mg versus 3.4% with placebo at 68 weeks 1
• In patients with obesity and heart failure with preserved ejection fraction (HFpEF), semaglutide treatment reduced body weight by 9.8% compared with 3.4% with placebo 4

Mechanism of Action and Administration

• Semaglutide is a glucagon-like peptide-1 (GLP-1) receptor agonist that promotes weight loss through:

  • Appetite and hunger suppression
  • Decreased energy intake
  • Reduced fondness for fatty, energy-dense foods 5

• Proper titration is essential to minimize side effects:

  • Start at 0.25 mg once weekly for 4 weeks
  • Increase to 0.5 mg, then 1.0 mg, then 1.7 mg, and finally 2.4 mg once weekly 6
  • The optimal dose for weight loss is 2.4 mg once weekly 6

Benefits Beyond Weight Loss

• Semaglutide improves multiple cardiometabolic risk factors:

  • Blood pressure reduction
  • Improved lipid profile
  • Enhanced physical functioning and quality of life 1, 2

• In patients with obesity and HFpEF, semaglutide improved:

  • Kansas City Cardiomyopathy Questionnaire clinical summary score (13.7 points vs. 6.4 points with placebo)
  • 6-minute walk distance
  • Composite endpoint of death, heart failure events, and other clinical measures 4

Adverse Effects and Management

• Gastrointestinal symptoms are the most common side effects:

  • Nausea, diarrhea, constipation, and vomiting
  • Typically transient and mild-to-moderate in severity 2

• Management strategies include:

  • Slow titration schedule
  • Reducing meal size
  • Limiting alcohol and carbonated drinks
  • Avoiding high-fat diets 6

• Treatment discontinuation due to gastrointestinal events occurs in approximately 4.5% of patients on semaglutide vs. 0.8% on placebo 2

Clinical Recommendations

• The American Diabetes Association (2025) recommends GLP-1 receptor agonists with greater weight loss efficacy (semaglutide or tirzepatide) as preferred pharmacotherapy for people with diabetes and overweight/obesity 4

• Weight management pharmacotherapy should be continued beyond reaching weight loss goals to maintain health benefits, as sudden discontinuation often results in weight regain 4

• Evaluate treatment efficacy after 3-4 months on the maintenance dose; if <5% weight loss is achieved after 16 weeks on the maintenance dose, consider discontinuing the medication 6

• For those not reaching treatment goals, intensify treatment with additional approaches (e.g., metabolic surgery, additional pharmacologic agents, structured lifestyle management programs) 4

Semaglutide represents a significant advancement in obesity pharmacotherapy, offering substantial and sustained weight loss with improvements in cardiometabolic risk factors and quality of life.