Doctors across the US say drugs like Wegovy and Ozempic help many people lose weight, but they fail for about half of those who try them. This gap has pushed researchers to study why some bodies respond and others do not. They now see a path to custom treatment plans for obesity, much like those used for cancer patients today. These plans would match drugs and lifestyle changes to a person's unique biology.
Background
Obesity affects millions in the US. It raises risks for heart disease, diabetes, and other health issues. For years, people turned to diet and exercise. Then came GLP-1 drugs, first made for diabetes. These shots slow digestion and cut hunger. Wegovy, for example, leads to about 12% body weight loss on average. But when people stop taking it, most regain two-thirds of the lost weight. This shows obesity acts like a long-term condition, not a quick fix.
Use of these drugs has boomed. Medicaid prescriptions for GLP-1s jumped since 2019, driven by Ozempic and Mounjaro. Still, coverage stays limited. Only 13 state Medicaid programs pay for them to treat obesity directly. Medicare bans coverage for weight loss alone. Costs run high, often thousands a year, which blocks access for many.
Researchers link obesity to more than overeating. Genes, hormones, gut bacteria, and environment all play roles. GLP-1 drugs target one pathway: they mimic a gut hormone to control blood sugar and appetite. But with so many factors, one drug size does not fit all.
Key Details
New studies show why GLP-1s miss the mark for half of users. Some people lack the right receptors or have other blocks in their systems. Doctors now test blood, genes, and scans to spot these issues.
New Drugs in the Pipeline
Drug makers race to build better options. Oral pills top the list—no more weekly shots. Novo Nordisk's amycretin, a mix of GLP-1 and amylin, cut 13% of body weight in early tests. Orforglipron, another pill, matched shot results and helped people keep weight off after switching from semaglutide.
Triple agonists like retatrutide push further. They hit GLP-1, GIP, and glucagon paths. Trials showed up to 28.7% weight loss, plus less knee pain in people with obesity and joint issues. MariTide and eloralintide each hit 20% loss over months, with gains in blood pressure and cholesterol.
Viking Therapeutics' VK2735 comes in shot and pill forms. The shot took nearly 15% weight in three months; the pill got 12%. These target more hunger signals. Aardvark's ARD-101 curbs appetite 2.5 times more than fake pills in tests.
China firms join in. Hengrui's HRS9531, a GLP-1/GIP mix, passed phase 3 for weight loss.
Semaglutide also won approval for MASH, a liver disease tied to obesity. This opens new uses.
"Obesity is a chronic and complex disease requiring management throughout a person’s life," said Jaime Almandoz of UT Southwestern Medical Center.
Trials compare drugs head-to-head. Tirzepatide showed heart benefits over older diabetes meds. Dual drugs like survodutide match top weight loss with fewer side effects than triples.
Real-world data adds clues. People on these drugs eat less but keep some habits. Side effects like nausea hit hard at first but ease. Long-term use pairs with diet coaching for best results.
What This Means
Personalized care could change obesity treatment. Doctors might start with tests to pick the right drug or combo. One person may need a GLP-1 plus amylin hitter. Another could get a triple agonist if heart risks loom large. Gene tests could predict winners, skipping trial and error.
This mirrors cancer care. There, tumors get scanned for markers. Drugs match those markers. Obesity plans would do the same: profile hormones, metabolism, and inflammation. Behavioral therapy would pair with meds, as the World Health Organization now suggests for long-term use.
Access remains a hurdle. High prices and spotty insurance slow rollout. But if drugs cut heart attacks and diabetes, savings could follow. One study saw 39,000 fewer heart events with access to obesity treatments. Kidney and liver gains add up too.
In 2026, oral drugs debut. Medicare may cover obesity meds standalone. These shifts could reach more people. Doctors say mixing drugs, diets, and coaching will sustain weight loss. No rebound if treatment fits lifelong needs.
Patients already see gains. Waist sizes shrink, blood sugar steadies, energy rises. For non-responders to GLP-1s, new paths open. Trials wrap up, approvals near. The field moves from one-size-fits-most to care built for each body.
