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TIRZEPATIDE (ZEPBOUND®)





Acronyms


DRUGS IN CLASS


MECHANISM OF ACTION


FDA-APPROVED INDICATIONS


WEIGHT LOSS


RCT
SURMOUNT-1 trial - Tirzepatide vs Placebo for Weight Loss in Obese Patients Without Diabetes, NEJM (2022) [PubMed abstract]
  • The SURMOUNT-1 trial enrolled 2539 adults with a BMI ≥ 30 or a BMI ≥ 27 and at least one weight-related complication
Main inclusion criteria
  • Age ≥ 18 years
  • History of unsuccessful dieting
  • BMI ≥ 30 or ≥ 27 and 1 or more of the following:
    • Hypertension
    • Dyslipidemia
    • OSA
    • CVD
Main exclusion criteria
  • Diabetes
  • Previous bariatric surgery
  • Other weight loss drug within 90 days
Baseline characteristics
  • Average age 45 years
  • Female sex - 68%
  • Average body weight - 231 lbs (105 kg)
  • Average BMI - 38
Randomized treatment groups
  • Group 1 (630 patients): Tirzepatide 5 mg once weekly
  • Group 2 (636 patients): Tirzepatide 10 mg once weekly
  • Group 3 (630 patients): Tirzepatide 15 mg once weekly
  • Group 4 (643 patients): Placebo once weekly
  • Tirzepatide was initiated at a dose of 2.5 mg once weekly (or matching placebo) and was increased by 2.5 mg every 4 weeks during the dose-escalation period to reach a maintenance dose of up to 15 mg once weekly by week 20
Primary outcome: The coprimary end points were the percentage change in body weight from baseline to week 72 and a weight reduction of 5% or more at week 72
Results

Duration: 72 weeks
Outcome Tir 5 mg Tir 10 mg Tir 15 mg Placebo Comparisons
% change in body weight −15% −19.5% −20.9% −3.1% Tir (all doses) vs Placebo p<0.001
≥ 5% weight loss 85% 89% 91% 35% Tir (all doses) vs Placebo p<0.001
Body weight lost 35.5 lbs (16.1 kg) 48.9 lbs (22.2 kg) 52.0 lbs (23.6 kg) 5.3 lb (2.4 kg) N/A
Nausea 24.6% 33.3% 31% 9.5% N/A
Diarrhea 18.7% 21.2% 23% 7.3% N/A
Constipation 16.8% 17.1% 11.7% 5.8% N/A
Pancreatitis 0.2% 0.2% 0.2% 0.2% N/A
Gallbladder disease 0.8% 1.7% 1.0% 0.8% N/A
  • Treatment discontinuations due to adverse events were 4.3%, 7.1%, and 6.2% with 5 mg, 10 mg, and 15 mg of tirzepatide, respectively, and 2.6% with placebo
  • Gastrointestinal side effects were transient, mild to moderate in severity, and occurred primarily during the dose-escalation period

Findings: In this 72-week trial in participants with obesity, 5 mg, 10 mg, or 15 mg of tirzepatide once weekly provided substantial and sustained reductions in body weight.




SIDE EFFECTS


  • Reference [1]
Gastrointestinal Side effects
Side effect Placebo
(N=958)		 Tir 5 mg
(N=630)		 Tir 10 mg
(N=948)		 Tir 15 mg
(N=941)
Nausea 8% 25% 29% 28%
Diarrhea 8% 19% 21% 23%
Vomiting 2% 8% 11% 13%
Constipation 5% 17% 14% 11%
Abdominal Pain 5% 9% 9% 10%
Dyspepsia 4% 9% 9% 10%
Injection site reactions 2% 6% 8% 8%
Fatigue 3% 5% 6% 7%
Hypersensitivity reactions 3% 5% 5% 5%
Burping 1% 4% 5% 5%
Hair loss✝ 1% 5% 4% 5%
GERD 2% 4% 4% 5%
Flatulence 2% 3% 3% 4%
Abdominal distension 2% 3% 3% 4%
Dizziness 2% 4% 5% 4%
Hypotension‡ 0% 1% 1% 2%
✝ Hair loss in tirzepatide-treated patients was more common in women than men (7.1% vs 0.5%)
‡ Hypotension in tirzepatide-treated patients was more common in those receiving antihypertensives (2.2% vs 1.2%)











CONTRAINDICATIONS


PRECAUTIONS




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DOSING




LONG-TERM SAFETY


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