Big Clinical Trials on the Horizon for Obesity

Desktop and laptop computers are little miracle machines that can do all sorts of wild and insane things, but the history of figuring out how to interact with them was a long road. Early computers used punch cards, which were later replaced by keyboards modeled after typewriter keyboards. You can still do a lot with a keyboard, and some people prefer to use keyboards for their precision and speed in doing many tasks. What really changed the game, however, was the computer mouse. With the mouse, computers could take advantage of being graphical, not just text-based, and people could easily select, drag, move, and draw whatever they could see. This functionality was replicated with touchscreens, and now it’s easy enough for babies to perform actions that used to require dozens of keystrokes. Some people can navigate a computer with a keyboard, but for most people, current systems are much easier to navigate with the addition of a mouse or touchscreen.

For most people, navigating the systems we have for healthy body weight is not easy using simple willpower. In the U.S., somewhere around 3 in 4 adults are either overweight or obese.^[1] Obesity in particular is dangerous, and carries an increased risk of associated conditions (diabetes, metabolic syndrome, and heart issues) and consequences (reduced quality of life, early death).^[2] One of the key problems with obesity is that fat cells, which store excess energy in the form of free fatty acids, become overactive and convert some free fatty acids into chemicals and hormones that contribute to inflammation.^[3] These hormones are released into the bloodstream, causing low-grade inflammation and insulin resistance that disrupts basically every system in the body.^[3] This means that even with limited food intake, the problems can persist until a person loses weight and fat cells stop being overactive. Weight loss is the fundamental goal for dealing with obesity, and large amounts of weight loss are ideal, though even modest amounts (above  5% of body weight) can be beneficial.^[4,5]

For many people, weight loss has traditionally been seen as a problem of self-control and lifestyle choices. Research has shown that adopting a Mediterranean diet, exercise, and guided interventions are effective for some people, but for many, it’s like trying to draw a picture on a computer using a keyboard without a mouse.^[5] Lifestyle interventions alone have shown small but significant health improvements for some people, including the ability to process sugar - a key for those with diabetes.^[4,6] Most people can’t squeak by on lifestyle adjustments alone and need interventions. Until recently, the most effective and successful weight loss intervention (for eligible candidates) was bariatric surgery.^[4] Indeed, surgery that targets the digestive system is associated with more weight loss and better long-term outcomes than lifestyle changes alone.^[4] Unfortunately, some people compute that the drawbacks - limited accessibility, limited reversibility, and a small risk of complications - outweigh the benefits.^[4]

Luckily for those people, the cat’s out of the bag, and medical solutions are everywhere. Many of these mimic gut hormones that signal when we are full. Glucagon-like peptide-1 (GLP-1) is the most well-known of these, and medications that mimic it (called GLP-1 receptor agonists) are sold as Wegovy and Saxenda. These have been blockbuster medications, but while they are like computer mice, 2026 may be the year of the proverbial touchscreen. Ongoing clinical research trials are investigating oral GLP-1 receptor agonists that don’t require fasting beforehand.^[7] Other trials have looked at another gut hormone, glucose-dependent insulinotropic polypeptide (GIP), and have investigated combination medications that mimic both hormones in the pursuit of better results and longer-lasting doses that may only need to be taken monthly.^[8,9] Also on the horizon are treatments looking to activate the cells that release these hormones in the body, called enteroendocrine cells.^[10] These new medications act by making us feel full and helping to control appetite even in a world designed to get us to eat more and more of the least healthy (yet most delicious!) food ever seen on the planet. New technology, tested through clinical trials, may finally help weight loss click for some people.

Creative Director Benton Lowey-Ball, MWC, BS, BFA

References:

[1] NIDDK. Overweight & Obesity Statistics. U.S. Department of Health and Human Services. https://www.niddk.nih.gov/health-information/health-statistics/overweight-obesity Accessed December 22, 2025.

[2] Kuk JL, Rotondi M, Sui X, Blair SN, Ardern CI. Individuals with obesity but no other metabolic risk factors are not at significantly elevated all‐cause mortality risk in men and women. Clinical obesity. 2018 Oct;8(5):305-12. https://doi.org/10.1111/cob.12263

​[3] Rothberg AE, McEwen LN, Kraftson AT, Ajluni N, Fowler CE, Nay CK, Miller NM, Burant CF, Herman WH. Impact of weight loss on waist circumference and the components of the metabolic syndrome. BMJ open diabetes research & care. 2017 Feb 20;5(1). https://doi.org/10.1136/bmjdrc-2016-000341

[4] Tahrani AA, Morton J. Benefits of weight loss of 10% or more in patients with overweight or obesity: a review. Obesity. 2022 Apr;30(4):802-40. https://doi.org/10.1002/oby.23371

[5] Franz MJ, Boucher JL, Rutten-Ramos S, VanWormer JJ. Lifestyle weight-loss intervention outcomes in overweight and obese adults with type 2 diabetes: a systematic review and meta-analysis of randomized clinical trials. Journal of the Academy of Nutrition and Dietetics. 2015 Sep 1;115(9):1447-63. https://doi.org/10.1016/j.jand.2015.02.031

[6] Dombrowski SU, Knittle K, Avenell A, Araújo-Soares V, Sniehotta FF. Long term maintenance of weight loss with non-surgical interventions in obese adults: systematic review and meta-analyses of randomised controlled trials. Bmj. 2014 May 14;348. https://doi.org/10.1136/bmj.g2646

[7] Buckeridge C, Tsamandouras N, Carvajal‐Gonzalez S, Brown LS, Hernandez‐Illas M, Saxena AR. Once‐daily oral small‐molecule glucagon‐like peptide‐1 receptor agonist lotiglipron (PF‐07081532) for type 2 diabetes and obesity: two randomized, placebo‐controlled, multiple‐ascending‐dose phase 1 studies. Diabetes, Obesity and Metabolism. 2024 Aug;26(8):3155-66.

[8] Jastreboff, A. M., Ryan, D. H., Bays, H. E., Ebeling, P. R., Mackowski, M. G., Philipose, N., ... & Pannacciulli, N. (2025). Once-Monthly Maridebart Cafraglutide for the Treatment of Obesity—A Phase 2 Trial. New England Journal of Medicine.

[9] Chakravarthy MV, Rodriguez R, Hergarden A, Elliott MA, Frias JP, Argüelles-Tello FA, Tenorio E, Rankin JE, Wu J, Krishnan S, Erlanson DA. Effects of CT-388, a once-weekly signaling-biased dual GLP-1/GIP receptor agonist, on weight loss and glycemic control in preclinical models and participants with obesity. Molecular Metabolism. 2025 Nov 28:102291. https://doi.org/10.1016/j.molmet.2025.102291

[10] Moyes CR, He S, Mathieu S, Lehman SL, Francisco MT, Vardy E, Terracina G, Galstian A, Murphy MJ, Poterewicz G, Kosinski D. Discovery of gut-targeted GPR40 agonist K-757 and GPR119 agonist K-833, a combination treatment for metabolic disorders. Journal of Medicinal Chemistry. 2025 Jul 25;68(15):15339-57. https://pubs.acs.org/doi/full/10.1021/acs.jmedchem.5c01030

Reference Style changed from APA to AMA January, 2026