SEMAGLUTIDE (WEGOVY®)



















STEP 1 Study - Semaglutide vs Placebo for Weight Loss in Adults Without Diabetes, NEJM (2021) [PubMed abstract]
  • The STEP 1 study enrolled 1961 overweight or obese adults without diabetes
Main inclusion criteria
  • Age ≥ 18 years
  • ≥ 1 failed attempt at dieting
  • BMI ≥ 30 or ≥ 27 with one weight-related condition (e.g. OSA, hyperlipidemia, CVD)
Main exclusion criteria
  • Diabetes
  • HgA1C ≥ 6.5%
  • Previous obesity surgery
  • History of chronic pancreatitis
  • Acute pancreatitis within 180 days
Baseline characteristics
  • Average age 46 years
  • Female sex - 74%
  • Average weight - 231 lbs (105 kg)
  • Average BMI - 38
Randomized treatment groups
  • Group 1 (1306 patients): Semaglutide 2.4 mg subcutaneously once weekly
  • Group 2 (655 patients): Placebo
  • Semaglutide was started at a dose of 0.25 mg once weekly and increased every 4 weeks over a period of 16 weeks to a target dose of 2.4 mg once weekly
  • All patients also received diet and exercise counseling
Primary outcome: Coprimary endpoints were the percentage change in body weight from baseline to week 68 and achievement of a reduction in body weight of 5% or more from baseline to week 68
Results

Duration: 68 weeks
Outcome Semaglutide Placebo Comparisons
Percent weight loss 14.9% 2.4% p<0.001
Weight loss 33.6 lbs (15.3 kg) 5.7 lbs (2.6 kg) Diff -28, 95%CI (-30 to -25.7)
≥ 5% weight loss 86.4% 31.5% p<0.001
≥ 10% weight loss 69.1% 12% p<0.001
≥ 15% weight loss 50.5% 4.9% p<0.001
Change in fasting glucose -8.35 mg/dl -0.48 mg/dl Diff โ€“7.87, 95%CI (โ€“9.04 to โ€“6.70)
Nausea 44.2% 17.4% N/A
Diarrhea 31.5% 15.9% N/A
Vomiting 24.8% 6.6% N/A
Constipation 23.4% 9.5% N/A
Hypoglycemia 0.6% 0.8% N/A
Drug discontinuation due to side effect 7% 3.1% N/A

Findings: In participants with overweight or obesity, 2.4 mg of semaglutide once weekly plus lifestyle intervention was associated with sustained, clinically relevant reduction in body weight.



STEP 8 trial - Wegovy vs Saxenda for Weight Loss in Overweight Adults, JAMA (2022) [PubMed abstract]
  • The STEP 8 trial enrolled 338 adults with BMI ≥ 30 or ≥ 27 and 1 or more weight-related comorbidities
Main inclusion criteria
  • Adults ≥ 18 years
  • BMI ≥ 30 or ≥ 27 with one weight-related condition (OSA, hyperlipidemia, CVD, hypertension)
  • ≥ 1 self-reported unsuccessful dietary weight loss effort
Main exclusion criteria
  • Diabetes
  • HgA1C ≥ 6.5%
  • Weight change ≥ 5 kg in last 90 days
Baseline characteristics
  • Average age 49 years
  • Female sex - 78.4%
  • Average BMI - 38
  • Average weight - 231 lbs (105 kg)
Randomized treatment groups
  • Group 1 (126 patients): Wegovy (semaglutide) 2.4 mg once weekly
  • Group 2 (127 patients): Saxenda (liraglutide) 3 mg once daily
  • Group 3 (85 patients): Placebo
  • Patients were randomized 3:1 to Wegovy or matching placebo or 3:1 to Saxenda or matching placebo. Wegovy and Saxenda treatment group assignments were not blinded.
  • Wegovy was titrated to 2.4 mg over 16 weeks. A 1.7 mg maintenance dose was permitted if 2.4 mg could not be tolerated
  • Saxenda was titrated over 4 weeks. If 3.0 mg dose was not tolerated, treatment could be restarted, with reescalation over 4 weeks.
Primary outcome: Percentage change from baseline in body weight at week 68
Results

Duration: 68 weeks
Outcome Wegovy Saxenda Comparisons
Primary outcome (% weight loss) 15.8% 6.4% p<0.001
People with ≥ 10% weight loss 71% 26% p<0.001
People with ≥ 20% weight loss 39% 6% p<0.001
Actual weight loss 34 lbs (15.3 kg) 15 lbs (6.8 kg) diff 8.5, 95%CI[11.2 to 5.7]
Discontinued treatment 13.5% 27.6% N/A
Nausea 61% 59% N/A
Constipation 39% 32% N/A
Diarrhea 28% 18% N/A
Vomiting 25% 21% N/A
  • Weight loss for the pooled placebo groups was 1.9%
  • Among subjects who did not stop treatment, 86.2% received the 2.4-mg dose of semaglutide and 95.7% received the 3.0-mg dose of liraglutide

Findings: Among adults with overweight or obesity without diabetes, once-weekly subcutaneous semaglutide compared with once-daily subcutaneous liraglutide, added to counseling for diet and physical activity, resulted in significantly greater weight loss at 68 weeks.





  • Reference [1]
Side effect Wegovy
(N=1261)
Placebo
(N=2116)
Nausea 44% 16%
Diarrhea 30% 16%
Vomiting 24% 6%
Constipation 24% 11%
Abdominal pain 20% 10%
Dyspepsia 9% 3%
Abdominal distension 7% 5%
Belching 7% < 1%
Flatulence 6% 4%






























Weeks Weekly Dose
1 through 4 0.25 mg
5 through 8 0.5 mg
9 through 12 1 mg
13 through 16 1.7 mg
Week 17 and onward 2.4 mg