Tirzepatide Once Weekly for the Treatment of Obesity - SURMOUNT-1

Contribution To Literature:

The SURMOUNT-1 trial showed that among patients with obesity, once-weekly tirzepatide reduced body weight substantially as compared to placebo.


The goal of the trial was to assess the efficacy and safety of tirzepatide, a glucose-dependent insulinotropic polypeptide (GIP) receptor and glucagon-like peptide-1 (GLP-1) receptor agonist versus placebo in overweight or obese adults without diabetes.

Study Design

The SURMOUNT-1 trial was a phase 3, multicenter, double-blind, placebo-controlled trial at 119 sites in nine countries. Patients were randomized in 1:1:1:1 fashion to tirzepatide 5 mg (n = 630), 10 mg (n = 636), or 15 mg (n = 630); or placebo (n = 643) administered subcutaneously once weekly for 72 weeks in addition to lifestyle intervention. Tirzepatide was initiated at 2.5 mg weekly and increased by 2.5 mg every 4 weeks.

  • Total enrolled participants: 2,539
  • Median duration of follow-up: 72 weeks
  • Mean patient age: 44.9 years
  • Percentage female: 67.5%
  • White race: 70.6%

Inclusion criteria:

  • Age ≥18 years
  • Body mass index (BMI) of ≥30 kg/m2 or ≥27 kg/m2 and a weight-related complication
  • One or more unsuccessful dietary effort to lose weight

Exclusion criteria:

  • Diabetes
  • Change in body weight of >5 kg within 90 days before screening
  • Previous or planned surgical treatment for obesity
  • Medication treatment that promoted weight loss 90 days prior to screening

Other salient features/characteristics:

  • Mean body weight, 104.8 kg (mean BMI, 38.0 kg/m2)
  • Mean waist circumference, 114.1 cm
  • Average 14.4-year duration of obesity
  • 40.6% with prediabetes at baseline

Principal Findings:

The co-primary endpoint, percentage change in body weight from baseline to week 72, for tirzepatide vs. placebo (p < 0.001):

  • 5 mg: −15%
  • 10 mg: −19.5%
  • 15 mg: −20.9%
  • Placebo: −3.1%

The co-primary endpoint, a weight reduction of ≥5% at week 72, for tirzepatide vs. placebo (p < 0.001):

  • 5 mg: 85.1%
  • 10 mg: 88.9%
  • 15 mg: 90.9%
  • Placebo: 34.5%

Secondary outcomes for tirzepatide vs. placebo:

     Weight reduction of ≥20%:

  • 5 mg: 30.0%
  • 10 mg: 50.1%
  • 15 mg: 56.7%
  • Placebo: 3.1%

     Change in baseline to week 72 in waist circumference:

  • 5 mg: −14.0 cm
  • 10 mg: −17.7 cm
  • 15 mg: −18.5 cm
  • Placebo: −4.0 cm

Serious adverse events: 5 mg, 6.3%; 10 mg, 6.9%; 15 mg, 5.1%; vs. placebo, 6.8%

Treatment discontinuation due to adverse events: 5 mg, 4.3%; 10 mg, 7.1%; 15 mg, 6.2%; vs. placebo, 2.6%


The results of this trial show that, among overweight or obese patients, tirzepatide leads to substantial weight loss as compared to placebo. Most patients are able to have a 5% weight loss. At the 10 mg and 15 mg dose, tirzepatide leads to a nearly 20% reduction in body weight. Compared to other obesity pharmacotherapies and GLP-1 agonists, tirzepatide appears to have a larger mean reduction in body weight, although this needs to be studied in dedicated trials. Importantly, adverse effects consisted of mild-to-moderate gastrointestinal events occurring at the dose-escalation period and were similar to previous studies of incretin-based therapies. Overall, the study provides good evidence for the use of tirzepatide in obese or overweight patients without diabetes. Long-term outcomes data are also awaited.


Jastreboff AM, Aronne LJ, Ahmed NN, et al., on behalf of the SURMOUNT-1 Investigators. Tirzepatide Once Weekly for the Treatment of Obesity. N Engl J Med 2022;387:205-16.

Editorial: Rosen CJ, Ingelfinger JR. Shifting Tides Offer New Hope for Obesity. N Engl J Med 2022;387:271-3.

Clinical Topics: Cardiovascular Care Team, Diabetes and Cardiometabolic Disease, Prevention, Diet

Keywords: Anti-Obesity Agents, Body Mass Index, Diet, Gastrointestinal Tract, Glucagon-Like Peptide 1, Glucagon-Like Peptide-1 Receptor, Glucose, Incretins, Life Style, Metabolic Syndrome, Obesity, Overweight, Prediabetic State, Primary Prevention, Waist Circumference, Weight Loss, Weight Reduction Programs

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