Consider medications, surgery for long-term weight-loss success for midlife women

Key takeaways :

• Bariatric surgery is more effective for obesity and overweight vs. diet, exercise and medication.
• Physicians should discuss weight gain risks with midlife women and advise lifestyle modifications for prevention.

PHILADELPHIA — Midlife women with obesity should be counseled about anti-obesity medications and bariatric surgery in addition to diet, exercise and behavioral therapy for long-term weight-loss success, according to a speaker.

Health care providers should discuss weight gain with women, because weight gain and body composition changes in midlife increase risks for diabetes, high blood pressure, high cholesterol, fatty liver disease and heart disease, said a speaker at the Annual Meeting of The Menopause Society.

Weight gain is a common concern for midlife women, with large cohort studies demonstrating weight gain of 0.8 lb to 1.5 lb per year, according to Maria Daniella Hurtado, MD, PhD, an endocrinologist and assistant professor of medicine in the division of endocrinology, diabetes, metabolism and nutrition at Mayo Clinic in Jacksonville, Florida. In midlife women, not only is aging associated with behavioral changes linked to decreased physical activity and muscle mass, but menopause itself is linked to body fat redistribution, which puts women at risk for visceral adiposity, noted Hurtado. One in four midlife women meets overweight criteria and two in five meets obesity criteria, Hurtado said.

“We must be aware of these changes to proactively prevent them and/or provide the adequate tools to manage excess adiposity,” Hurtado told Healio. “Overweight and obesity are highly prevalent diseases that are often underdiagnosed, undertreated and mistreated.”

Holistic weight loss

Providing midlife women with a holistic weight management approach is beneficial because it includes weight-gain prevention, medical symptom management and evidence-based treatments, according to Hurtado.

Vasomotor symptoms are linked to weight gain and quality of life, which impact sleep quality, diet and exercise, all factors that can affect our weight, Hurtado noted. Therefore, treating vasomotor symptoms with menopause hormone therapy, cognitive behavioral therapy, hypnosis or other nonhormonal pharmacologic interventions can help to prevent weight gain.

The Pittsburgh Women’s Healthy Life Project found that a daily intake of 1,300 calories with reduced saturated fat and cholesterol can prevent weight gain during the menopause transition. The Woman’s Health Initiative demonstrated that a low-fat diet with increased vegetable, fruit and grain intake without purposeful calorie restriction prevented weight gain in postmenopausal women. In addition, lifestyle interventions, such as dietary changes, in conjunction with behavior modification and physical activity are successful in weight loss, with 3% to 5% weight loss in moderate lifestyle intervention programs and 7% to 10% weight loss in intensive programs. However, Hurtado noted, weight regain is common when solely utilizing lifestyle interventions for weight loss.

Hurtado recommends offering a multimodal approach to patients wherein lifestyle interventions are the “backbone of treatment” but patients are also offered pharmacotherapy and/or bariatric surgery for successful weight-loss and weight-gain prevention.

Anti-obesity medications, surgery

Utilizing both lifestyle interventions like diet, behavior modification and exercise with pharmacotherapy and/or bariatric surgery in midlife women with overweight or obesity can aid in sustained weight loss and prevent weight regain.

Currently, the following anti-obesity medications are approved by the FDA:

• phentermine;
• orlistat (Xenical, GlaxoSmithKline);
• phentermine/topiramate (Qsymia, Vivus);
• naltrexone/bupropion (Contrave, Currax Pharmaceuticals);
• liraglutide (Saxenda, Victoza; Novo Nordisk); and
• semaglutide (Wegovy, Ozempic; Novo Nordisk).

While there are no studies comparing the effectiveness of these drugs, based on clinical trial results, semaglutide should be considered the first-line therapy, according to Hurtado. The pivotal trial for semaglutide showed that participants lost 15% of their weight after 1 year of semaglutide 2.4 mg subcutaneously weekly compared with 2.4% in the placebo group, according to Hurtado. In addition, one in three patients lost more than 20% of their body weight, which is weight-loss results normally seen with bariatric surgery. Furthermore, soon-to-be published data have revealed that semaglutide decreases the risk of cardiovascular events in people with overweight or obesity and a history of cardiovascular disease, Hurtado noted.

Phentermine/topiramate combination is a good alternative to semaglutide, Hurtado said, as it is also effective and is the most cost-effective anti-obesity medication based on current U.S. pricing. In the pivotal trial for phentermine/topiramate, participants lost an average of 10.4% of their weight after 1 year of the maximum drug dose compared with 1.2% for placebo. For cost in the U.S., phentermine/topiramate is currently priced at $1,500 annually compared with $13,000 annually for semaglutide, according to Hurtado.

Unfortunately, Hurtado noted, anti-obesity medication discontinuation can lead to weight gain. In the STEP 4 maintenance trial, patients were given semaglutide for 20 weeks and were then randomly assigned to continue the drug or switch to placebo. Those who continued the drug continued losing weight while those on placebo started regaining weight. Hurtado addressed another concern commonly seen in clinical practice: the long-term use of phentermine, which is currently approved by the FDA for 12 weeks or less. Based on retrospective data on the use of phentermine, and the data of phentermine in combination with topiramate, there is evidence that compared to short-term use, long-term use of phentermine alone not only leads to more weight loss but does not increase the risk of cardiovascular events.

Hurtado said the future of anti-obesity medications is promising because there are many drugs currently on the market for other indications and in the pipeline, including retatrutide (Eli Lilly), cagrilintide/semaglutide (Novo Nordisk), AMG133 (Amgen), oral GLP-1 agonists and bimagrumab (Versanis Bio).

For bariatric surgery, Hurtado noted that it remains the most effective treatment for obesity, and it has greater efficacy and durability than any other anti-obesity treatment. Bariatric surgery is the only treatment with reliable data for decreased adiposity-related CV mortality, decreased cirrhosis, decreased end-stage renal disease, decreased cancer and decreased mortality, according to Hurtado.

“We must make people understand that obesity is a disease with a biologic basis that if left untreated can lead to serious health problems. We must amplify the message that weight problems can be effectively treated with appropriate tools,” Hurtado said. “Women should feel that they can mention this issue at their appointment without feeling stigmatized. As clinical providers, it is our responsibility to recognize that this is a common concern among women, and we should be prepared to offer an adequate treatment.”

For more information:

Maria Daniela Hurtado, MD, PhD, can be reached at hurtado.mariadaniela@mayo.edu.