Beyond the Shot: New Report Shows How to Make Obesity Drugs Work Long-Term

BOSTON, MA – February 24, 2026 – As blockbuster GLP-1 drugs like Wegovy and Zepbound reshape obesity treatment, a new report suggests the secret to their long-term success may lie beyond the pharmacy. Metabolic health company knownwell today released its inaugural Clinical Outcomes Report, presenting compelling real-world data from over 1,800 patients that demonstrates a comprehensive care model can produce more durable weight loss and significantly reduce a key side effect: muscle loss.

The report, analyzing patient outcomes from February 2023 to February 2025, found that individuals in knownwell's program lost an average of 15.9% of their body weight. Crucially, the company reported 50% lower lean mass loss compared to benchmarks from published GLP-1 clinical trials. Furthermore, 97% of patients sustained their weight loss over a 12-month period with minimal regain, a durability rate the company claims is nearly five times higher than published national averages.

These findings arrive at a critical juncture for the healthcare industry, which is grappling with the staggering cost and uncertain long-term value of GLP-1 medications. The data suggests that how these powerful drugs are administered—as part of an integrated, supportive system rather than a standalone prescription—could be the key to unlocking their full clinical and economic potential.

"Prescribing a medication is not the same as treating obesity," said Dr. Angela Fitch, Chief Medical Officer and Co-Founder of knownwell, in a statement accompanying the release. "Obesity is a chronic, complex disease, and our patients deserve comprehensive, longitudinal care that addresses the whole person, not just their weight. These results confirm what we see every day in our clinics."

Addressing the Achilles' Heel of Modern Weight Loss

While the efficacy of GLP-1 agonists in promoting weight loss is undisputed, a growing body of evidence has highlighted a significant concern: the loss of lean body mass. Major clinical trials for leading drugs, such as the STEP 1 trial for semaglutide and the SURMOUNT-1 trial for tirzepatide, have shown that lean mass can account for anywhere from 25% to as much as 45% of the total weight lost. This loss of muscle can negatively impact metabolic rate, strength, and long-term health, making it harder to maintain weight loss over time.

knownwell's report directly confronts this issue. By leveraging SECA body composition measurements, the company's claim of cutting lean mass loss by half represents a potentially major advancement in obesity medicine. This outcome is attributed to its multidisciplinary care model, which goes far beyond a simple prescription. Patients are supported by a team that includes physicians, registered dietitians, pharmacists, and health coaches who work to optimize medication response while implementing personalized nutrition and exercise plans aimed at preserving muscle.

This holistic approach also appears to solve the problem of weight regain, a common issue when patients discontinue GLP-1 therapy. The report's finding that 97% of patients maintained their weight loss with 5% or less regain over a year stands in stark contrast to the widespread industry concern about adherence and durability. The results were consistent across virtual, hybrid, and in-person care settings, suggesting the model is scalable and flexible.

A Potential Blueprint for Payors and Health Systems

The financial implications of knownwell's findings are profound. Health systems and insurance payors are facing immense pressure from the high cost of GLP-1 therapies, leading many to question the long-term return on investment. With list prices exceeding $1,000 per month per patient, the key questions for payors revolve around adherence and durability: will patients stay on the drug, and will the health benefits persist long enough to offset the cost by reducing obesity-related comorbidities?

knownwell's data provides a potential answer. By demonstrating a path to sustained outcomes and better body composition, the company makes a strong case that investing in a comprehensive care infrastructure is essential for maximizing the value of these expensive medications. This model offers a compelling alternative to the purely transactional, medication-focused telehealth platforms that have proliferated in recent years.

"When obesity medicine is delivered in a comprehensive care model, patients achieve stronger, more durable outcomes," Dr. Fitch noted. "As obesity management medication adoption grows, health systems and payors need models that ensure those investments translate into durable health improvements. That's what knownwell was built to do."

This integrated strategy is becoming a clear trend among innovators in the space. Companies like Calibrate and Found have also built programs combining GLP-1s with intensive coaching, reporting impressive weight loss results that they, too, attribute to their holistic methods. The key differentiator for knownwell appears to be its deep integration of obesity medicine with primary care, allowing patients to manage their metabolic health and broader medical needs within a single, coordinated system.

Aligning with a Shifting Policy Landscape

The move towards comprehensive obesity care is not just a business trend; it is increasingly reflected in national and global health policy. In December 2025, the Centers for Medicare & Medicaid Services (CMS) announced the BALANCE model, a voluntary program designed to test coverage for GLP-1s when they are combined with evidence-based lifestyle support. This initiative signals a recognition by federal regulators that medication alone is insufficient.

Similarly, the World Health Organization (WHO) recently issued its first-ever guidelines on using GLP-1s for obesity, recommending them for long-term treatment but explicitly stating that they must be part of a comprehensive strategy that includes person-centered care and healthier environments. The WHO cautioned that medication alone will not solve the global obesity crisis.

Against this backdrop, knownwell's report serves as a timely real-world case study for the very models that policymakers are beginning to champion. By providing concrete data on improved lean mass, high adherence, and long-term durability, the company is offering a tangible blueprint for how to treat obesity as the chronic disease it is—moving beyond the promise of a single shot to the practice of sustainable, whole-person health.