Addressing obesity and diabetes requires more than just medication.
Pharmacological agents demonstrating the potential to induce a substantial reduction, up to a quarter, in body weight may soon become available. Retatrutide, proven effective in treating obesity during a phase 2 trial, represents the latest addition to a cohort of drugs generating considerable enthusiasm within the fields of obesity and diabetes. Semaglutide, an agonist targeting GLP-1, gained approval from the US Food and Drug Administration for diabetes treatment (marketed as Ozempic) in 2017. In 2021, it received approval for obesity or overweight treatment (as Wegovy), and a trial evaluating its impact on renal disease, cardiovascular risks, and kidney mortality was prematurely halted due to observed efficacy. Subsequent to these developments, a series of drugs, modulating digestion and appetite by influencing the body’s hormonal response to food, has entered the market. Tirzepatide, a dual agonist for GLP-1 and glucose-dependent insulinotropic polypeptide (GIP), obtained approval for overweight treatment in 2023. Retatrutide is part of an emerging class of triple agonists, targeting GLP-1, GIP, and glucagon receptors. The competition among pharmaceutical companies to produce the most effective treatment is intense, given the potential for a lucrative market, with billions of dollars at stake. Companies lacking such agents are actively pursuing their development.
There is cautious optimism for patients as well. For individuals with obesity confined to their homes, exhausted by all other approaches, a simple-to-administer, effective drug could be transformative. High BMI contributes to millions of global deaths and disability-adjusted life-years. The World Obesity Federation predicts that over 1 billion people will be affected by obesity by 2030 without intervention. Despite the challenges faced by traditional public health approaches in controlling non-communicable diseases, interest in these drugs is evident. However, the associated uncertainties and caveats necessitate a high degree of caution.
A recent research letter in JAMA highlights an association between the use of GLP-1 agonists for weight loss and the risk of pancreatitis, gastroparesis, and bowel obstruction. Long-term safety data for these drugs are scant, and concerns become more pressing as indications potentially expand. Guidelines recommend treatment with anti-obesity agents for BMI of 35 kg/m² or more, raising questions about the potential extension to individuals with a BMI of 25–35. Manufacturers are likely working to broaden the indications, with these drugs already being used not only for medical reasons but also for weight loss desires. While large-scale prescription of medications is accepted for common conditions, our understanding of the efficacy and safety of this drug class remains in its early stages. Long-term surveillance studies examining the risks and benefits across different patient groups are imperative.
The cost of these drugs is also a pertinent issue. Currently approved medications range from $300 to $1300 for a four-week treatment period. Weight loss is sustained only during drug use, and upon cessation, weight can be regained. The costs of chronic treatment, for individuals and health systems alike, could be substantial. Nevertheless, the potential financial savings associated with effectively treating diabetes and obesity-related diseases, including various cancers, are considerable. The estimated lifetime medical costs for obese 10-year-old children in the USA range from $9.4 to $14.0 billion. Obesity leads to productivity losses through sick leave, long-term incapacity, and early retirement, with significant economic consequences. However, it is evident that the costs are unlikely to be borne equally, exacerbating inequities between those able to afford treatment and those burdened with greater disease in socially deprived groups and poorer countries.
While a simple pill or injection may undoubtedly benefit some patients, it cannot be the exclusive solution to the complexities of obesity. Obesity is a result not only of an individual’s circumstances and behavior but also of societal factors shaped by global food markets and trade agreements. Comprehensive approaches are required to mitigate the effects of the obesogenic environment, particularly against an international industry that promotes the overproduction of inexpensive food and drinks. Increasing physical activity, normalizing and facilitating walking and cycling for commuting, implementing sugar taxes, and restricting the marketing of high-energy, high-fat, ultra-processed foods are essential measures. Prevention must be the cornerstone upon which all other initiatives are built.
