#372 Mission Slimpossible Part 2: Oral GLP-1 agonists for weight loss
CLINICAL QUESTION
Are oral GLP-1 agonists effective for weight loss?
BOTTOM LINE
In adults with obesity, oral semaglutide in a new high-dose formulation (50mg daily; not available in Canada) can result in ~15% body weight loss at 68 weeks (versus 2% placebo), with 69% of people losing at least 10% of their body weight (versus 12% placebo). Mean weight loss with the currently available 14mg formulation is ~5%.
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EVIDENCE
- Results statistically different unless indicated.
- One industry-funded randomized, controlled trial (RCT)1 on weight loss:
- 667 adults with obesity and no diabetes (105 kg, BMI=38), given semaglutide 50mg (modified formulation) orally or placebo for 68 weeks, plus lifestyle intervention. At 68 weeks:
- Mean weight loss: 15% (16kg) versus 2% (2.5kg) placebo.
- Proportion of patients with >10% weight loss: 69% versus 12% placebo.
- Withdrawals due to adverse events: 6% versus 4% placebo (statistics not provided):
- Mainly gastrointestinal.
- Gallbladder disorders (mainly cholelithiasis) 4% versus 1% placebo (no statistics).
- “Altered skin sensation” (examples: paresthesia, sensitive skin): 13% versus 1% placebo (no statistics).
- 667 adults with obesity and no diabetes (105 kg, BMI=38), given semaglutide 50mg (modified formulation) orally or placebo for 68 weeks, plus lifestyle intervention. At 68 weeks:
- Systematic reviews (3-11 RCTs, 1300-9890 patients) where weight loss was secondary outcome (up to 14mg semaglutide):
- ~3kg more weight lost than placebo at 26-82 weeks.2-5
- Gastrointestinal side effects 4-9% versus 1-2% placebo.3
- Industry-sponsored RCT (weight loss as secondary outcome) not in above reviews.6 1606 patients with diabetes (96kg, BMI=34), given semaglutide 14mg, 25mg, or 50mg. At 52 weeks:
- Mean weight loss: 5.4% [4.4kg (14mg)], 6.6% [6.7kg (25mg)], 7.3% [8kg (50mg)]. No statistics 25 versus 50mg doses.
- >10% weight loss: 14% (14mg), 29% (25mg), 37% (50mg), no statistics 25 versus 50mg.
- Withdrawals due to adverse events: 10% (14mg), 12% (25mg), 13% (50mg). No statistics.
CONTEXT
- Weight loss is dose dependent, with efficacy similar between semaglutide 50mg oral daily and 2.4mg subcutaneous weekly.6,7
- Oral semaglutide used in RCTs (i.e., 50 mg) is a different formulation than the one currently available (i.e., 3-14mg) (altered to improve bioavailability).1
- Low-dose oral semaglutide (14mg) daily costs~$250/month; not covered by most insurance plans. Cost of higher dose not yet known.
- Other oral GLP-1 agonists in development; may have similar benefits.8
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