European Primary Care Cardiovascular Society

Discontinuation of dual GIP and GLP-1 receptor agonist leads to weight regain in people with obesity or overweight

News - Oct. 16, 2023

SURMOUNT-4 Trial results: the impact of tirzepatide on maintenance of weight reduction and benefits of continued therapy*

Presented at the EASD annual meeting 2023. Naveed Sattar, MD, PhD (Glasgow, UK) presented SURMOUNT-4 background, rationale design and baseline characteristics, and Louis Aronne, MD (New York, NY, USA) presented SURMOUNT-4 study efficacy and safety results.

Introduction and methods

Tirzepatide is a dual GIP and GLP-1 receptor agonist, which is approved for the management of T2D and currently under review for chronic weight management. In SURMOUNT-1, robust reductions in body weight were seen in patients with obesity without T2D taking tirzepatide. According to obesity management guidelines, pharmacologic interventions should be used long-term to prevent weight regain. It is unknown what the effects of tirzepatide are on the maintenance of weight reductions in people with obesity. The aim of the current study was to determine whether weight reduction by tirzepatide is maintained in patients discontinuing therapy, and determine the benefits of continued therapy.

SURMOUNT-4 was a randomized, double-blind, multicenter, placebo-controlled trial. 783 adults with obesity or overweight (BMI ≥30 kg/m² or ≥27 kg/m² with at least 1 weight-related complication [hypertension, dyslipidemia, obstructive sleep apnea, or CVD]; mean BMI: 38.6 kg/m²; weight: 107 kg; waist circumference: 115.1 cm) without diabetes first entered a 36-week open-label phase with tirzepatide treatment, followed by a 52-week double-blind treatment period (n=670 patients) with tirzepatide at maximally tolerated doses (MTD) of 10 mg or 15 once weekly or matching injectable placebo. In the open-label phase, treatment doses of tirzepatide were gradually escalated to the MTD at week 20 (2.5 mg dose increases in each escalation cycle). At randomization, 49 patients (7.3%) were treated with tirzepatide 10 mg and 621 patients (92.7%) were treated with tirzepatide 15 mg. After the total treatment period, there was a 4-week safety follow-up period. People could participate in the study when they had at least one self-reported unsuccessful dietary effort to lose body weight. 290 patients (86.6%) in the placebo group and 310 patients (92.5%) in the tirzepatide group completed the study.

The primary endpoint was the percent change in body weight from randomization (36 weeks) to end of treatment period (88 weeks).

Main results

//Efficacy outcomes//

Safety outcomes


In the SURMOUNT-4 trial, continued treatment with tirzepatide was superior to discontinued therapy with placebo for the maintenance of body weight reduction in people with obesity or overweight with at least one weight-related complication. Treatment with tirzepatide MTD for 88 weeks led to clinically meaningful body weight reductions of 25%. Participants who discontinued treatment with tirzepatide for one year regained body weight, but not to baseline weight (9.5% below baseline). Safety outcomes in this study were consistent with the previously reported safety profile of tirzepatide and the GLP-1RA class in people with obesity.

- Our reporting is based on the information provided at the EASD annual meeting -

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