#295 Mission Slimpossible: Semaglutide for weight loss
CLINICAL QUESTION
Is semaglutide effective for weight loss?
BOTTOM LINE
Used with lifestyle changes, 2.4mg weekly subcutaneous semaglutide resulted in an average 10-15% loss in weight (10-15kg) over 68 weeks versus 2-3% (3-4kg) with placebo. Most (70-80%) semaglutide participants lost 5% or more of their body weight. About ¾ of patients experienced gastrointestinal side effects, but few stop. Weight regain occurs once the medication is stopped.
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EVIDENCE
- Four industry-funded, randomized, placebo-controlled trials (RCTs) of subcutaneous semaglutide 2.4mg/week for weight loss, plus lifestyle interventions (counseling, diet, and physical activity).1-4 Baseline weight ~96-105kg.
- 1961 non-diabetics.1 After 68 weeks:
- Mean weight loss: 15% of weight (15kg) versus 2% (3kg, placebo).
- Proportion who lost ≥5% weight: 86% versus 32% (placebo), number need to treat (NNT)=2.
- Lost ≥10%: 69% versus 12%, NNT=2.
- Weight loss plateaued ~week 60.
- Adverse effects:
- Gastrointestinal: 74% versus 48% (placebo), number needed to harm (NNH)=3.
- Withdrawal due to adverse effects: 7% versus 3%, NNH=25.
- RCT of semaglutide with more intensive lifestyle intervention found similar [weight loss 16% (17kg) versus 6% (6kg, placebo)].2
- Dose-finding RCT, 1210 diabetics. Given semaglutide 2.4mg/week, 1.0mg/week or placebo.3 After 68 weeks:
- Mean weight loss: 10% (2.4mg), 7% (1mg) and 3% (placebo)
- Proportion who lost ≥5% weight: 69% (2.4mg) versus 57% (1mg) versus 29% (placebo), 2.4mg versus 1mg: NNT=9.
- Adverse effects similar between doses.
- Weight maintenance RCT. 803 non-diabetics given semaglutide 2.4mg/week for 20 weeks then randomized to continue semaglutide or switch to placebo. After 48 weeks:4
- Continued semaglutide lost 8% versus 7% gain (placebo).
- 1961 non-diabetics.1 After 68 weeks:
- Weight loss with oral semaglutide studied as secondary outcome in cardiovascular disease and glucose-lowering trials. Participants weight loss was 4.6% (4.2kg) versus 0.9% (0.8kg, placebo) at 15.9 months in largest RCT.5
- High-dose semaglutide (0.4mg daily) superior to liraglutide (3mg daily) in semaglutide-sponsored RCT:
- Weight loss: 14% semaglutide (17kg) versus 8% liraglutide (8kg).
- Weight loss similar between 0.1mg daily semaglutide and liraglutide.6
- Semaglutide titration in RCTs: Every 4 weeks as tolerated.
- Semaglutide 2.4mg not currently available (Canada), but lower doses are.7
- 1mg weekly costs ~$200/month.8
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