Pharmacotherapy in Obesity Management
June 25, 2025
Innovations in Diabetes & Metabolic Care | Summer 2025
Historically stigmatized as a result of poor diet or exercise habits, obesity is increasingly recognized as a multicausal, relapsing disease state.
“Obesity is now being looked at as a complex, chronic condition,” says William Fryfogle, PharmD, BCPS, BCACP, a clinical pharmacist at the University Hospitals Diabetes & Metabolic Care Center. “Medicine is evolving to acknowledge and manage the comorbidities, genetic and psychosocial factors contributing to metabolic syndrome and weight gain.
Medical weight loss experts at the UH Diabetes & Metabolic Care Center offer a collaborative practice model, working together to provide patients with a multidisciplinary and personalized approach to achieving a healthy weight. At University Hospitals Cleveland Medical Center, patients are often referred to the center’s weight management program by their primary care physician.
“After our endocrinology providers thoroughly review each patient’s medical history and goals, our dietitians and behavioral health specialists help tailor an individualized plan for diet and lifestyle modifications,” Dr. Fryfogle says. “Historically, diet and exercise have been the recommended first-line therapies for weight loss,” says Dr. Fryfogle. “However, an update from the American College of Cardiology [ACC] calls this into question. This report recommends starting patients on GLP-1s at the beginning of treatment, in addition to lifestyle modifications, to optimize cardiovascular health.”
Evolution of weight-loss medications
Early medications targeting weight loss — including amphetamine-based appetite suppressants and fenfluramine/phentermine (fen-phen) — were largely withdrawn due to significant safety concerns.
The 2000s marked a turning point with the approval of safer therapies, including Bupropion/Naltrexone (Contrave) and Phentermine/Topiramate (Qsymia). However, newer medications began to show greater effectiveness.
Starting in 2014, the emergence of glucagon-like peptide-1 (GLP-1) receptor agonists further transformed the landscape of pharmacologic weight management. Originally developed to treat type 2 diabetes, GLP-1s mimic an incretin hormone that enhances insulin secretion, suppresses glucagon, slows gastric emptying and promotes satiety. Saxenda® (liraglutide) was the first GLP-1 agonist approved for the treatment of obesity.
Wegovy® (semaglutide) received U.S. Food and Drug Administration (FDA) approval for weight loss in 2021, marking the first introduction of a new weight loss drug in seven years. In clinical trials, patients who received the once-weekly injection began experiencing unprecedented weight reductions. Cardiometabolic markers such as blood pressure, lipid profiles and HbA1c also showed improvement. Zepbound (tirzepatide) followed, receiving FDA approval in 2023 for the treatment of obesity or overweight with weight-related medical conditions.
Prior to GLP-1s, obesity medications showed limited benefit — on average, patients would lose less than 10 percent of their body weight. “Treating obesity usually requires a weight loss of at least five percent to be clinically significant. However, even this can be a struggle with non-GLP-1 medications,” Dr. Fryfogle says. “Wegovy has been shown to help patients lose close to 15 percent, and Zepbound is closer to a 20 percent average loss of body weight.”
Due to their extraordinary effectiveness, demand has surged. Clinical pharmacists play a vital role in improving access to GLP-1 medication management, adjusting titrations, monitoring comorbidities and identifying contraindications.
“We find that Wegovy and Zepbound offer the most weight loss benefit at their highest doses, but we start at a low dose and work up to a higher titration to minimize gastrointestinal side effects,” Dr. Fryfogle says. “When patients can only see their providers every couple of months, pharmacists in a collaborative practice can see them much sooner and more often. This allows the pharmacist to write prescriptions to titrate dosages and help patients reach their goals sooner.”
When patients are referred to Dr. Fryfogle, he reviews their blood work and comorbidities, allowing him to start, stop or adjust medications to help patients achieve target glucose levels, blood pressure or cholesterol. “While GLP-1s are one part of the puzzle, we also identify medications to treat other conditions that may cause weight gain so we can transition patients to a better choice,” he says.
Another important aspect of pharmacological care is helping patients navigate insurance coverage for weight-loss medications. One path to broader acceptance is FDA approval for conditions beyond obesity. Wegovy is now approved to help reduce the risk of heart attack and stroke, and Zepbound is approved to treat obstructive sleep apnea.
“When we find the right medication for a patient, but their insurance denies it, that is a significant barrier we are working to address,” Dr. Fryfogle says. “I believe access will continue to improve as the benefits of these medications in preventing weight-related comorbidities are better understood.”
For more information, call the UH Diabetes & Metabolic Care Center at 216-435-1071.
Contributing Expert:
William Fryfogle, PharmD, BCPS, BCACP
Clinical Pharmacist
University Hospitals Cleveland Medical Center