Ozempic and Wegovy have been hailed as groundbreaking for individuals grappling with obesity or excess weight.
A 2021 clinical trial revealed that 86.2% of over 800 participants experienced "clinically significant" weight reduction after receiving weekly doses of 2.4 mg semaglutide (marketed as Ozempic and Wegovy) for 68 weeks.
Despite these encouraging statistics, they also signify that 13.8% of individuals did not achieve clinically significant weight loss.
Physicians emphasize the importance of patients recognizing they could belong to either category — responder or non-responder — even though data suggests a higher likelihood of response.
"As with any other class of medication, one prescription may not suit every patient perfectly," notes Dr. Meghan Garcia-Webb, MD, who holds triple board certification in internal medicine, lifestyle medicine, and obesity medicine. "It's crucial that patients avoid solely relying on one medication for all their health progress."
The factors contributing to a patient's placement in the non-responder group can vary, and sometimes, multiple factors are at play.
Dr. Michael L. Glickman, MD, elucidates that "success" with a GLP-1 medication entails shedding more than 5% of body weight within three months of treatment.
"However, in clinical practice, our aim is to achieve a weight loss of at least 10-15%, which can yield more significant improvements in metabolic health," explains Glickman, a family medicine, lifestyle medicine, and obesity medicine specialist with triple board certification and the founder of Revolution Medicine. "The response to a weight loss medication can be somewhat unpredictable. Research indicates that each medication harbors a subgroup of individuals termed 'non-responders.'"
Why? These are the five rationales health professionals cite as the most prevalent.
Lifestyle changes
While occasionally sidelined, studies on semaglutide (such as this one involving over 1,900 adults published in 2021) incorporated lifestyle interventions for both the control and drug-receiving cohorts.
"For optimal outcomes with a GLP-1 medication, patients typically should adhere to the six fundamental tenets of Lifestyle Medicine," advises Glickman. These principles encompass:
* Eating a plant-forward diet
* Regular exercise
* Managing stress
* Avoiding substance use
* Maintaining strong social relationships with family and friends
Are these groundbreaking? Not particularly, yet Glickman asserts their indispensability for individuals, whether pursuing weight loss or not, and underscores their potential to hinder the efficacy of anti-obesity medications.
A study from 2023 highlighted another rationale why exercise is crucial for individuals utilizing weight loss medications: As individuals shed pounds, they may also lose muscle mass.
Engaging in physical activity can mitigate this loss and its correlated hazards, such as injury.
Not taking medication as prescribed
Maintaining consistent adherence to the correct dosage is crucial for achieving success.
"If the medication isn't taken as directed, such as skipping doses or not adhering to timing or dosage instructions, its effectiveness may be compromised," explains Dr. Yoshua Quinones, MD, an internist certified by the board and affiliated with Medical Offices of Manhattan, who contributes to LabFinder.
Various factors contribute to this issue, ranging from inadequate education on medication administration to forgetfulness. Additionally, studies indicate that sustained weight loss is more likely with long-term medication usage.
A 2022 clinical trial revealed that individuals who discontinued 2.4 mg weekly doses of semaglutide regained approximately two-thirds of their lost weight within a year. Similarly, Quinones notes that immediate cessation of medication can impede weight loss outcomes.
"GLP-1 agonists often necessitate a certain duration of treatment before their full benefits manifest," he emphasizes. "Premature discontinuation or failure to adhere to the prescribed regimen may result in unmet treatment objectives."
It's worth noting that the trials monitored patients for over a year — 68 weeks.
A 2021 trial indicated that achieving responder status by week 20 was indicative of successful weight loss of 15%, with over 96% of these participants subsequently experiencing weight reduction.
According to a Reuters report featuring analysis from pharmacy benefits manager Prime Therapeutics, only 32% of individuals reported continued usage of Ozempic and Wegovy after one year.
However, not everyone can afford prolonged medication use. Drugs like Wegovy can carry a monthly price tag of approximately $1,000.
Accessibility is a significant concern, as insurance programs, including Medicare, don't consistently cover weight-loss medications. Moreover, efforts to expand Medicare coverage to include anti-obesity drugs have stalled, as reported by Scientific American. Even for those who can afford the medication, shortages have posed challenges for patients.
In addition to access, patients may contend with side effects such as gastrointestinal discomfort. For some, these adverse effects are sufficient grounds for discontinuation.
"The side effects of medication often diminish over time, but if they're severe, some patients may decide the potential benefits aren't worth the discomfort," notes Garcia-Webb. "The primary objective of these medications is to enhance people's health and well-being, not to necessitate exhausting their sick leave."
Other medical issues
An individual might contend with undisclosed or insufficiently addressed medical conditions.
"Some medical conditions — like hypothyroidism, sleep apnea, chronic insomnia, among others — can hinder weight loss endeavors and should be managed before commencing weight management medication," advises Garcia-Webb.
Furthermore, a person could grapple with an eating disorder.
"For individuals grappling with obesity alongside binge eating disorder, the GLP-1 agonist may sometimes alleviate binge eating behavior, though not invariably," Garcia-Webb notes.
A 2024 review highlighted that preliminary findings from small-scale pilot studies suggest GLP-1s may mitigate certain eating disorders, but researchers emphasized the necessity for more robustly gathered evidence.
Insulin resistance
Ozempic is formulated to manage diabetes and assist in reducing A1C levels. However, research, such as a 2022 narrative review, suggests that individuals may experience less weight loss with GLP-1 medications.
"When there's an existing metabolic disorder, reversing those abnormalities becomes more challenging, especially if they've been established over an extended period," remarks Glickman.
The reaction is physiological.
"In patients with type 2 diabetes, their body's responsiveness to GLP-1 and its ability to stimulate insulin secretion are diminished," elucidates Quinones. "Typically, GLP-1 helps regulate blood sugar by prompting the pancreas to release insulin post-meals. However, this response may be less robust compared to individuals without diabetes. This reduced reaction to GLP-1 can complicate blood sugar management in diabetic patients, necessitating alternative treatment approaches or adjustments in medication dosage."
Medication interference
Individuals using a GLP-1 medication concurrently with other drugs might encounter reduced weight loss.
"Patients might also face challenges shedding pounds if they're taking certain medications alongside a GLP-1 that can induce weight gain, such as specific antidepressants and beta blockers," notes Glickman.
Garcia-Webb concurs and urges individuals to discuss their concurrent medication usage with their healthcare providers before initiating a GLP-1 medication, particularly if weight loss isn't occurring as expected.
