The prevalence of obesity is rapidly rising across the globe; within the United States alone, more than one third of adults are living with this chronic disease. Several anti-obesity medications are approved for the treatment of obesity and should be used in conjunction with lifestyle modification. Depending on the proportion of weight loss achieved, improvements can be seen in obesity-related comorbidities including reduction in type 2 diabetes and cardiovascular risk. However, weight regain is a challenge and may be brought about by withdrawal of anti-obesity medication.[ In this article, Jaime P. Almandoz, MD, MBA, shares his perspectives on the use and withdrawal of weight loss pharmacotherapy.
Social media outlets are full of stories about celebrities who have lost weight with the new generation of incretin medications. Some of these medicines are approved for treating obesity, whereas others are approved for type 2 diabetes.[
Clinics are full of patients who have taken these medications, with unprecedented improvements in their weight, cardiometabolic health, and quality of life. What happens when patients stop taking these medications? Or more importantly, why stop them? Although these drugs are very effective for weight loss and treating diabetes, there can be adverse effects, primarily gastrointestinal, that limit treatment continuation. Nausea is the most common side effect and usually diminishes over time. Slow dose titration and dietary modification can minimize unwanted gastrointestinal side effects. Drug-induced acute pancreatitis, a rare adverse event requiring patients to stop therapy, was seen in approximately 0.2% of people in clinical trials.
Medications Effective But Cost Prohibitive?
Beyond adverse effects, patients may be forced to stop treatment because of medication cost, changes in insurance coverage, or issues with drug availability. Insurance coverage and manufacturer discounts can make treatment affordable,[ but anti-obesity medicines are not covered by Medicare nor by many employer-sponsored commercial plans.
Changes in employment or insurance coverage, or expiration of manufacturer copay cards, may require patients to stop or change therapies. The increased prescribing and overall expense of these drugs have prompted insurance plans and self-insured groups to consider whether providing coverage for these medications is sustainable.
Limited coverage has led to significant off-label prescribing of incretin therapies that are not approved for treating obesity,[ and compounding pharmacies selling peptides that allegedly contain the active pharmaceutical ingredients.
Stopping Equals Weight Regain
Obesity is a chronic disease like hypertension. It responds to treatment and when people stop taking these anti-obesity medications, this is generally associated with increased appetite and less satiety, and there is subsequent weight regain and a recurrence in excess weight-related complications.
The STEP-1 trial extension showed an initial mean body weight reduction of 17.3% with weekly semaglutide 2.4 mg over 1 year.[ On average, two thirds of the weight lost was regained by participants within 1 year of stopping semaglutide and the study’s lifestyle intervention. Many of the improvements seen in cardiometabolic variables, like blood glucose and blood pressure, similarly reverted to baseline.
There are also 2-year data from the STEP-5 trial with semaglutide; 3-year data from the SCALE trial with liraglutide; and 5-year nonrandomized data for agents such as metformin, topiramate, and bupropion, that showed durable, clinically significant weight loss for obesity, including an average weight loss of 10.4% after a median follow-up of 4.4 years. In this 5-year analysis, 428 patients who were treated at an academic weight management clinic, who were classified as obese or overweight, were treated with anti-obesity medication and tracked for an average of 2 years. The main outcome measures were percentage weight loss, weight reduction targets, and other predictors of long-term weight loss. Over the mean duration of 4.4 years, the researchers documented an average weight loss of 10.4%. While 40.2% of patients maintained their weight loss with those medications, about 51% of maximum weight loss was regained.
These data together demonstrate that medications are effective for durable weight loss if they are continued. However, this is not how obesity is currently treated. Anti-obesity medications are prescribed to less than 3% of eligible people in the United States, and the average duration of therapy is less than 90 days.[ This treatment length is not sufficient to see the full benefits most medications offer and certainly does not support long-term weight maintenance.
In addition to maintaining weight loss from medical therapies, a recent study showed that incretin-containing anti-obesity medication regimens were effective for treating weight regain and facilitating healthier weight after bariatric surgery.
Chronic therapy is needed for weight maintenance because several neurohormonal changes occur owing to weight loss. Metabolic adaptation is the relative reduction in energy expenditure, below what would be expected, in people after weight loss. When this is combined with physiologic changes that increase appetite and decrease satiety, many people create a positive energy balance that results in weight regain.[ This has been observed in reality TV shows such as The Biggest Loser: It’s biology, not willpower.
Unfortunately, many people — including healthcare professionals — don’t understand how these changes promote weight regain and patients are too often blamed when their weight goes back up after medications are stopped. This blame is greatly misinformed by weight-biased beliefs that people with obesity are lazy and lack self-control for weight loss or maintenance. Nobody would be surprised if someone’s blood pressure went up if their antihypertensive medications were stopped. Why do we think so differently when treating obesity?
The prevalence of obesity in the United States is over 40% and growing.[ We are fortunate to have new medications that on average lead to 15% or greater weight loss when combined with lifestyle modification. However, these medications are expensive and the limited insurance coverage currently available may not improve. From a patient experience perspective, it is distressing to have to discontinue treatments that have helped to achieve a healthier weight and then experience regain.
People need better access to evidence-based treatments for obesity, which include lifestyle interventions, anti-obesity medications, and bariatric procedures. Successful treatment of obesity should include a personalized, patient-centered approach that may require a combination of therapies, such as medications and surgery, for lasting weight control.
Leave a Reply