The current state of obesity management appears better than ever. Care is more patient-centric than it has been in the past, and there is a broader range of management options with high efficacy, safety, and even cardiovascular benefit. What is more, there has been a paradigm shift in the understanding of obesity as a chronic disease.
Historically, obesity management has been the responsibility of the patients themselves. Individuals were thought to just need more self-discipline involving calorie restriction, adequate physical activity, and other elements of lifestyle modification and were stigmatized for not successfully losing weight. However, while lifestyle modification continues to be the foundation of obesity management, this strategy is limited. Lifestyle changes typically result in weight loss of only about three-five percent, and this is usually not sustained in the long-term.
The Look AHEAD trial evaluated interventions for patients with type 2 diabetes, a population for whom obesity is a common problem. Intensive lifestyle interventions, including counseling, reduced calorie intake with meal replacement products, and at least 175 minutes per week of moderate-intensity physical activity, were shown to produce underwhelming weight loss and cardiovascular results. During the 10-year follow-up period, modest weight loss was reported in only six percent of the intervention group vs. three percent of the placebo group. Clearly, strict regimens for diet and exercise are not sufficient to manage obesity. Something else must be going on.
It is now understood that a patient's efforts to restrict energy intake to induce weight loss can be counteracted by adapted biological responses to weight loss that can reduce energy expenditure out of proportion to reductions in body mass, including hormonal changes that actually increase appetite. In other words, regardless of self-discipline and personal effort to follow diet and exercise recommendations, the body itself may not be so willing to adhere.
Enter Anti-obesity Medications:
When added to lifestyle modifications, anti-obesity medications amplify their effects, through mechanisms that reduce energy intake, decrease hunger signals, and increase metabolism. The most recent FDA-approved class of medications for the chronic management of obesity in adults include injectable incretins: two glucagon-like peptide-1 (GLP-1) receptor agonists, semaglutide (Wegovy) and liraglutide (Saxenda), and tirzepatide (Zepbound), a dual glucose-dependent insulinotropic polypeptide (GIP) and GLP-1 receptor agonist.
In adults with overweight or obesity, adding semaglutide to lifestyle interventions promotes weight loss of about 15 percent of body weight, and with liraglutide, about eight percent of body weight at one year. Tirzepatide boasts strong evidence for weight loss as an anti-obesity medication for adults with overweight or obesity, sustaining weight loss of five-20 percent at roughly 1.5 years when added to lifestyle interventions. Of note, these results occurred in randomized trials of predominately White adults.
The news is particularly good for adults with diabetes, as these anti-obesity medications perform the dual role of controlling weight and hyperglycemia. For example, semaglutide resulted in a mean weight loss of roughly 10 percent at 68 weeks in adults with type 2 diabetes and overweight or obesity, with a mean reduction in HbA1c of 1.6 percent. In trials ranging from 40-72 weeks, tirzepatide 15 mg once weekly resulted in weight loss ranging from five-15 percent, with a mean reduction in HbA1c of 2.07%-2.34%. (It should be noted that semaglutide and liraglutide are marketed under different brand names with differing dosages, depending on the indication. Tirzepatide, however, has one brand name and dosage for both indications.)
General Recommendations and Considerations for Anti-obesity Medications:
The American Association of Clinical Endocrinologists/American College of Endocrinology and the Endocrine Society both recommend considering anti-obesity medications for adults with an initial body mass index (BMI) ≥ 30 kg/m2 or ≥ 27 kg/m2 and at least one obesity-related complication requiring more than six months of obesity management, if they are not able to successfully lose weight or maintain weight loss with lifestyle modifications alone.
Weight loss goals should be targeted based on each patient's values and preferences along with reasonable expectations regarding the effects of anti-obesity medications on the percentage of weight loss. Treatment goals may also include improvement, remission, or resolution of obesity-related complications (such as dyslipidemia, hypertension, hepatic steatosis, and obstructive sleep apnea), control of cravings, improvement in quality of life, and long-term weight maintenance. Differences among the mediations in efficacy, cautions, warnings, and adverse effects (for example, gastrointestinal effects ranging from nausea to gastrointestinal reflux disease [GERD]) must also be considered.
Obesity is a chronic disease that requires long-term management. But the outlook is more promising than ever thanks to the anti-obesity medications now on the market. Discussions between patients and clinicians regarding obesity management strategies should include consideration of these medications in addition to lifestyle changes for weight loss.
For additional information, see the DynaMedex topics on Anti-Obesity Medications for Adults and Anti-Obesity Medications for Adults With Diabetes.
