#392 Mission Slimpossible, Part 3: Tirzepatide for weight loss
CLINICAL QUESTION
Is tirzepatide effective for weight loss?
BOTTOM LINE
Tirzepatide 10-15mg/week results in ~15-20% weight loss versus 3% placebo at 72 weeks. Most patients on tirzepatide lose at least 10% body weight (78-84% versus ~20% placebo). Weight regain occurs when medication stopped. More weight loss occurs with tirzepatide versus semaglutide (~20% versus ~14%) based on one open-label, tirzepatide-sponsored randomized controlled trial (RCT).
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EVIDENCE
- All results statistically significant unless indicated.
- Four industry-run, placebo-controlled RCTs:1-4 Tirzepatide 10-15mg subcutaneous weekly. Baseline weight: 101-107kg. All patients received lifestyle. Excluded: Diabetic retinopathy, macular edema, unstable thyroid disease.1-3
- 2539 without diabetes.1 At 72 weeks:
- Mean weight loss: ~20% versus 3% placebo.
- Proportion who lost 10% weight: 78-84% versus 19% (placebo), number needed to treat (NNT)=2.
- Stopping for adverse effects (mostly gastrointestinal): ~7% versus 3% (placebo), number needed to harm (NNH)=25
- Alopecia (~5% versus 0.9% placebo, NNH=25), dizziness (~4% versus 2.3% placebo, NNH=59)
- 579 without diabetes.2 Randomized following lifestyle intervention. At 72 weeks,
- Weight loss 18% (21.5kg) versus 2.5% (3.5kg) gain (placebo).
- Stopping for adverse events: 11% versus 2% (placebo).
- 938 with diabetes.3 At 72 weeks:
- Weight loss: 13-15% (13-15kg) versus 3% (placebo: 3kg).
- Lost 10% weight: 61-65% versus 9% (placebo), NNT=2.
- Stopping for adverse effects (mostly gastrointestinal): 4% (10mg), 7% (15mg), 4% (placebo).
- Withdrawal RCT.4 670 without diabetes. Tirzepatide for 36 weeks then randomized to continue tirzepatide or placebo. After additional 52 weeks:
- Weight change: 6% loss (tirzepatide) versus 14% gain (placebo).
- 2539 without diabetes.1 At 72 weeks:
- Two head-to-head, tirzepatide-sponsored RCTs:5,6
- 751 without diabetes.5 Open-label tirzepatide 10-15mg versus semaglutide 1.7-2.4mg weekly. At 72 weeks,
- Weight loss: 20% (23kg) tirzepatide versus 14% (15kg) semaglutide
- Lost 10% weight: 82% versus 61% semaglutide, NNT=5.
- Stopping for gastrointestinal adverse effects: 2.7% versus 5.6% semaglutide.
- Other RCT uninterpretable [suboptimal semaglutide dosing (1mg)].6
- 751 without diabetes.5 Open-label tirzepatide 10-15mg versus semaglutide 1.7-2.4mg weekly. At 72 weeks,
CONTEXT
- Tirzepatide is approved for weight loss in Canada.7
- GLP-1 receptor agonists: Associated with pancreatitis, bowel obstruction and gastroparesis (each up to 7-9/1000 patient-years).8
- Dosing: 2.5mg weekly, titrate by 2.5mg every 4 weeks.
- 5mg dose: 15% weight loss.1
- Cost (30-day):9 ~$450-880.
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Pricey for now , not likely to be covered by ODB
Canot wait to see when this will be approved for weight loss in Canada, will follow closely
what is mechanism of dizziness as a side effect
excellent
expensive
na