Once-weekly treatment with tirzepatide can produce clinically meaningful and sustained weight loss for at least 3 years in adults with overweight or obesity who do not have diabetes, according to new research being presented at this year’s European Congress on Obesity (ECO) in Malaga, Spain (11-14 May). The findings also indicate that females and those without obesity-related complications may be more responsive to tirzepatide treatment.
The study, led by Dr Luca Busetto from the University of Padova in Italy and colleagues from Eli Lilly and Company that manufacture tirzepatide, is a continuation of the SURMOUNT-1 phase 3 trial of tirzepatide, a medication approved in the EU and USA for obesity and type 2 diabetes treatment.
“Our long-term analysis of tirzepatide establishes that clinically relevant weight loss can be sustained for up to 3 years in a diverse population of adults with overweight or obesity but not diabetes, regardless of age, BMI, and duration of obesity at the outset of the study”, said Dr Busetto. “But not everyone responds to medication to the same degree and we identified a greater chance of successful weight loss in a group with a higher proportion of females and those with no medical conditions linked to obesity.”
Tirzepatide works by mimicking the glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) hormones that are naturally secreted by the gut after a meal, which stimulates insulin secretion. It also reduces appetite by slowing down the time it takes the stomach to empty and interacting with areas in the brain harbouring GLP-1 receptors to signal fullness or satiety.
Tirzepatide was approved in November 2023 by the US Food and Drug Administration (FDA) (Zepbound) and in the EU in June 2024 (Mounjaro) for weight management in adults with obesity or overweight with at least one weight-related condition (such as high blood pressure, type 2 diabetes or high cholesterol).
In 2022, the SURMOUNT-1 trial initially found that adults randomised to tirzepatide for 72 weeks lost on average 15% to 21% of their initial weight depending on the dose [1]. This new analysis focuses on 700 of these participants (64% females, average age 48 years) randomised to receive tirzepatide (5, 10, or 15 mg) who were treatment adherent (at least 75% doses received), all of whom initially had either obesity (body mass index, or BMI, of greater than 30kg/m²), or overweight (a BMI of at least 27 kg/m²) and prediabetes.
The researchers examined the average percentage change in body weight from randomisation to week 176 (3 years) as well as time to reach 20% weight reduction to classify participants into three groups.
The associations between participants’ group and characteristics at the start of the study as well as weight loss plateau outcomes were then assessed. Weight loss plateau was defined as less than 5% weight change over 3 months after initial body weight reduction and over all subsequent 3-month intervals. The groups were comparable in average age, duration of obesity, current smoker status, and BMI.
The analysis identified three patterns of weight loss trajectories: participants in Group 1 (248) experienced a relatively steady weight reduction, losing around 10% of their body weight, and reached an early weight loss plateau; those in group 2 (226) experienced faster early body weight reduction (losing around 20%) and later weight loss plateau; while group 3 (226) had the fastest body weight reduction (losing about 30%) and the longest time to weight plateau (see figure in notes to editors).
As Dr Busetto explains: “Adults in Group 1 were on average almost 10% lighter than their initial body weight after 3 years. Whereas participants in Group 3, with the highest proportion of females and those with no medical conditions linked to obesity, lost another 20%, so their overall average weight loss was about 31%.”
Additionally, the percentage reaching a weight loss plateau at the end of the 3-year treatment period differed significantly between the groups, ranging from 87.6% of participants in Group 2 (198/226) to 87.1% of Group 1 (216/248), and 81.4% (184/226) of Group 3.
Among those who hit a weight loss plateau by the end of the study, the majority of participants in Group 1 and 2 reached a weight plateau at an average of 24 weeks (74.5% [161] and 48.0% [95] respectively) when compared to Group 3 (17.4%; 32). In contrast, the majority of participants in Group 3 reached a weight plateau much later, between week 36 and 48 (82.7%; 152).
“Everyone hits a weight loss plateau at some point, no matter which weight loss intervention they use”, explained Dr Busetto. “GLP-1 and GIP are just two of eight hormones that control hunger and weight, and eventually, the other hormones signal the body’s protective mechanisms to make changes to prevent more weight loss.”
He added: “Despite identifying three different patterns of weight loss trajectories, most participants maintained clinically meaningful weight loss over 3 years regardless of age, duration of obesity and BMI. Even modest weight loss can lead to important health benefits. Losing at least 5% of body weight cuts the risk of developing diabetes and meaningfully improves blood pressure and cholesterol. Losing 15% of body weight is the sweet spot at which people tend to reap most health benefits.”
He concluded: “The findings could provide deeper insights into the efficacy of tirzepatide across different demographics and medical histories, potentially allowing for more individualised treatment plans and goals.”
The trial uncovered no new safety issues; the most common side effects were nausea, diarrhoea, and constipation.
Article Publication Date
11-Apr-2025
COI Statement
Luca Busetto (LB) has received payment of honoraria from Eli Lilly, Novo Nordisk, Boehringer Ingelheim, Pfizer, Bruno Farmaceutici, Regeneron, Rythm Pharmaceuticals and Pronokal.