Tirzepatide for weight loss

Clinical question

Is tirzepatide effective for weight loss?

Bottom line

Tirzepatide 10 to 15 mg per week results in 15% to 20% weight loss in patients versus 3% (placebo) at 72 weeks. Most patients on tirzepatide lose at least 10% body weight (78% to 84% vs 20% placebo). More weight loss occurs with tirzepatide than semaglutide (20% vs 14%) based on 1 open-label, tirzepatide-sponsored randomized controlled trial (RCT).

Evidence

Results are statistically significant unless indicated. There are 4 industry-run, placebo-controlled RCTs of weekly 10- to 15-mg subcutaneous tirzepatide injections.^1-4 Baseline patient weight was 101 to 107 kg; all received lifestyle intervention. Those with diabetic retinopathy, macular edema, and unstable thyroid disease were excluded.^1-3

• Of 2539 patients without diabetes¹ at 72 weeks:

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    Mean weight loss 20% body weight (10 to 15 mg) vs 3% (placebo). Proportion of patients who lost 10% or more body weight: 78% to 84% vs 19% (placebo), number needed to treat (NNT)=2.
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    Adverse effect stop rate (mostly gastrointestinal): 7% vs 3% (placebo), number needed to harm (NNH)=25.
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    Proportion of patients experiencing alopecia 5% vs 0.9% (placebo; NNH=25), dizziness 4% vs 2.3% (placebo; NNH=59).
• Of 579 patients without diabetes² randomized following lifestyle intervention at 72 weeks:

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    Weight loss 18% body weight (21.5 kg) vs 2.5% (3.5 kg) weight gain (placebo). Adverse effect stop rate: 11% vs 2% (placebo).
• Of 938 patients with diabetes³ at 72 weeks:

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    Weight loss 13% to 15% body weight (13 to 15 kg) vs 3% (placebo; 3 kg).
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    Proportion of patients who lost 10% or more body weight: 61% to 65% (10 to 15 mg) vs 9% (placebo).
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    Adverse effect stop rate (mostly gastrointestinal): 4% (10 mg), 7% (15 mg), 4% (placebo).

• Tirzepatide was given to 670 patients for 36 weeks, then patients were randomized to continue or switch to placebo.⁴ After an additional 52 weeks, 6% weight loss (tirzepatide) vs 14% weight gain (placebo).

• There were 2 head-to-head, tirzepatide-sponsored RCTs^5,6 of 751 patients without diabetes⁵: open-label tirzepatide 10 to 15 mg vs semaglutide 1.7 to 2.4 mg weekly. At 72 weeks:

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    Weight loss 20% body weight (23 kg) tirzepatide vs 14% (15 kg) semaglutide.
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    Proportion of patients who lost 10% or more body weight: 82% tirzepatide vs 61% semaglutide, NNT=5.
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    Proportion of patients stopping due to adverse gastrointestinal effects: 2.7% tirzepatide vs 5.6% semaglutide.
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    Other RCT uninterpretable (suboptimal semaglutide dosing [1 mg]).⁶

Context

Glucagon-like peptide-1 receptor agonists are associated with pancreatitis, bowel obstruction, and gastroparesis (up to 7 to 9/1000 patient-years each).⁷ The cost of a 30-day supply of pens is $450 to $880.

Implementation

Tirzepatide starting dose 2.5 mg weekly with titration by 2.5 mg every 4 weeks as tolerated (maximum 15 mg). The 5 mg/week dose can result in 15% weight loss.¹ Tirzepatide was discontinued in RCTs³ when body mass index was 18.5 kg/m² or less. Patients on hormonal contraception should add barrier contraception for 4 weeks after starting tirzepatide and with dose increases due to potential drug interaction.⁸

Tools for Practice articles are adapted from peer-reviewed articles at http://www.toolsforpractice.ca and summarize practice-changing medical evidence for primary care. Coordinated by Dr Adrienne J. Lindblad, articles are developed by the Patients, Experience, Evidence, Research (PEER) team and supported by the College of Family Physicians of Canada and its Alberta, Ontario, and Saskatchewan Chapters. Feedback is welcome at toolsforpractice@cfpc.ca.