Obesity is a major global health crisis impacting every corner of the world. The global prevalence of obesity, defined as having a body mass index (BMI) equal to or greater than 30 kg/m2, is expected to rise from 14% of the world’s population in 2020 to 24% by 2035, or 1.9 billion people [World Health Organisation, 2024].
14% of the world’s population in 2020 and 24% of the world’s population in 2035 fight a BMI greater than 30 – a total of 1,9 billion people
Obesity is a chronic disease, and it results from a complex relationship of genetic, environmental, and lifestyle factors. The implication is significant increases in the risk of numerous diseases, including T2 diabetes, cardiovascular disease, and certain types of cancer. Over the last years the medical insight and knowledge has increased a lot. Managing obesity effectively requires a multi-factorial approach that combines diet, physical activity, behaviour changes, and medical interventions.
Recent advancements in obesity treatment include the development of GLP-1 (glucagon-like peptide-1) receptor agonists have revolutionized the treatment opportunities with 10-20% weight loss. These medications mimic the action of the natural hormone GLP-1, which helps regulate appetite and food intake. By enhancing this signalling pathway, GLP-1 effectively promote weight loss by reducing appetite, increasing feelings of fullness after eating, and even slowing gastric emptying [Drucker 2022, Angelidi et al. 2022, Lopez-Jimenez et al. 2023].
While these mechanisms are beneficial for weight loss, the slowing of gastric motility also leads to GI side effects such as nausea, vomiting, bloating, and constipation (Seino et al., 2020). These side effects result from prolonged gastric distension and altered digestive function, which stimulates the vagal pathways responsible for nausea and gut discomfort (Wadden et al., 2021).
There are notable differences in the side effects experienced by males and females when using GLP-1 receptor agonists, with females generally more likely to report adverse events. These differences may be attributed to various factors, including the higher prevalence of gastrointestinal conditions among females and sex-specific pharmacokinetic differences. Females often have a slower drug clearance rate, which can lead to higher exposure to the drug and consequently more adverse effects (Kautzky-Willer et al., 2023).
According to the literature, gastro-intestinal adverse events during GLP-1 therapy usually develop in 40–70% of treated patients, although they have sometimes been reported in up to 85% [Gorgojo-Martínez et al. 2023]. Clinical observations presented that gastro-intestinal side effects may lead to the temporary or permanent discontinuation of GLP-1 treatment. Interruption of therapy has been reported to occur in up to 12% of GLP-1 treated patients (vs. ~2% in those treated with placebo), and permanent discontinuations range between 1.6–6% of treated patients (vs. <1% with placebo) [Kushner et al. 2020, Aroda et al. 2022, Wharton et al. 2022].
…gastro-intestinal adverse events during GLP-1 therapy usually develop in 40–70% of treated patients….
In the real medical practice persistence with GLP-1 therapy has been found to range between 40% and 60% [Mody et al. 2021, Uzoigwe et al. 2021]. Withdrawal from therapy leads to weight regain even with continuing lifestyle intervention [Gorgojo-Martínez, et al. 2023]. In addition, a reduced appetite and rapid weight loss can lead to deficiencies in essential nutrients such as vitamins (A, D, E, K, and B-complex), minerals (iron, calcium, magnesium), and proteins.
Beyond discomfort, these symptoms can significantly degrade quality of life by causing continuous distress and limiting daily activities (Seino et al., 2020). These side effects not only reduce the effectiveness of the treatment but also negatively impact patients’ quality of life, leading to frustration and discontinuation (Wadden et al., 2021). An additional significant challenge in managing GLP-1 therapy is that the time spent addressing side effects during doctor-patient interactions often detracts from meaningful discussions about obesity management, reducing the focus on long-term health strategies (Gorgojo-Martínez et al., 2023).
These issues highlight the need for comprehensive management strategies that address both the primary therapeutic goals of GLP-1 agonists and the associated side effects. Improving the tolerability of GLP-1 therapy could potentially enhance treatment adherence, leading to better long-term outcomes in obesity management (Pratley et al., 2018).
