November 2023
Tirzepatide yields substantial weight loss in patients with or without diabetes

Weight reductions with higher doses approach those seen with bariatric surgery.

Subcutaneous tirzepatide (Mounjaro), a glucagon-like peptide-1 (GLP-1) receptor agonist and glucose-dependent insulinotropic polypeptide receptor agonist, is US Food and Drug Administration-approved for use at doses as high as 15 mg weekly for treating patients with type 2 diabetes. Two large trials have now demonstrated its effectiveness for treating patients with obesity.

In a study from 2022, 2500 adults without diabetes but with obesity (body mass index [BMI] 30 kg/m2 or higher or BMI 27 kg/m2 or higher with at least one weight-related complication) were randomised to lifestyle modification plus subcutaneous tirzepatide (at doses of 5mg, 10mg or 15mg weekly) or placebo for 72 weeks, including a 20-week dose-escalation period. The mean percentage changes in weight were −15%, −20% and −22%, respectively, in the tirzepatide groups and −3% in the placebo group. More than 50% of patients in the two higher- dose tirzepatide groups lost at least 20% of their baseline body weight compared with only 3% of patients in the placebo group.

In a 2023 study, 900 adults with BMI 27 kg/m2 or higher and glycosylated haemoglobin (HbA1c) of 7% to 10% (53 to 86 mmol/mol) were randomised to subcutaneous tirzepatide (10 mg or 15 mg) or placebo once weekly in addition to lifestyle modification. Patients continued their baseline diabetic medications (with sulfonylurea doses adjusted to prevent hypoglycaemia). After 72 weeks, the mean percentage changes in weight in the tirzepatide groups were −13% and −15%, respectively, compared with −3% in the placebo group. Mean changes in HbA1c were −2.0% in the tirzepatide groups and −0.5% in the placebo group.

In both studies, patients who received tirzepatide had greater improvements in various cardiometabolic risk factors than those who received placebo. The most common adverse effects of tirzepatide were mild-to-moderate nausea, vomiting and diarrhoea, primarily during the dose escalation phase.

Comment: Weekly subcutaneous tirzepatide appears to be an effective treatment for obesity in patients with and without diabetes, at least in the short term. Longer-term benefits and risks remain to be determined.

Bruce Soloway, MD, Associate Professor Emeritus of Family and Social Medicine, Albert Einstein College of Medicine, Bronx, New York, USA.

Jastreboff AM, et al. Tirzepatide once weekly for the treatment of obesity. N Engl J Med 2022; 387: 205-216.

Garvey WT, et al. Tirzepatide once weekly for the treatment of obesity in people with type 2 diabetes (SURMOUNT-2): a double-blind, randomised, multicentre, placebo-controlled, phase 3 trial. Lancet 2023; 402: 613-626.

N Engl J Med, Lancet