Insights from bariatric surgery further strengthened the biological model.
Patients undergoing weight-loss surgery often experienced improvements in blood glucose control within days—before significant weight loss occurred. This suggested that hormonal signals from the gut, not just calorie restriction, were altering metabolism.
One of those hormones, glucagon-like peptide-1 (GLP-1), became a central focus.
Initially approved by the U.S. Food and Drug Administration in 2005 for type 2 diabetes, GLP-1 receptor agonists mimic a naturally occurring hormone that regulates blood sugar, slows gastric emptying, and reduces appetite. Clinicians soon observed significant weight loss in patients receiving these medications.
In 2017, semaglutide (Ozempic) was approved for diabetes. A higher-dose formulation, Wegovy, was approved for obesity treatment in 2021 after clinical trials demonstrated average weight reductions of approximately 15%—results previously achievable primarily through bariatric surgery.
The next advance came with tirzepatide, which targets both GLP-1 and glucose-dependent insulinotropic polypeptide (GIP), another hormone involved in blood sugar and appetite regulation. In NIH-funded trials led by Ania Jastreboff, MD, PhD, associate professor of medicine (endocrinology) and of pediatrics (pediatrics endocrinology) at Yale School of Medicine, patients achieved weight reductions exceeding 20% of body weight—comparable to surgical outcomes. Tirzepatide is now approved under the brand names Mounjaro and Zepbound for type 2 diabetes and obesity.
These results represented the clinical culmination of decades of metabolic science. Medications were no longer simply suppressing appetite; they were targeting the biological systems that regulate energy balance.