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:

  • - 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.

  • - Adverse effect stop rate (mostly gastrointestinal): 7% vs 3% (placebo), number needed to harm (NNH)=25.

  • - 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:

  • - 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:

  • - Weight loss 13% to 15% body weight (13 to 15 kg) vs 3% (placebo; 3 kg).

  • - Proportion of patients who lost 10% or more body weight: 61% to 65% (10 to 15 mg) vs 9% (placebo).

  • - 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:

  • - Weight loss 20% body weight (23 kg) tirzepatide vs 14% (15 kg) semaglutide.

  • - Proportion of patients who lost 10% or more body weight: 82% tirzepatide vs 61% semaglutide, NNT=5.

  • - Proportion of patients stopping due to adverse gastrointestinal effects: 2.7% tirzepatide vs 5.6% semaglutide.

  • - 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