The Last Word

Weight and See?

Weight and See?

By Sam Gutterman

Obesity medications—a new way to fight obesity—have arrived. After many decades of vainly seeking a panacea, certain pharmaceutical companies have finally found it—and with it, the honeypot for big profits.

These medications have been the talk of the medical community, becoming Science magazine’s Breakthrough of the Year of 2023.

Four in 10 American adults are obese and almost 1 in 10 are morbidly obese. It is a chronic medical condition second only to smoking as the leading cause of preventable death.

However, just like everything else related to obesity—and I have written about obesity for more than 20 years—the associated issues are not straightforward and do not have simple solutions. For example, body mass index (BMI), a function of weight and height—the most commonly used metric of obesity—is losing favor because it focuses on weight, rather than where adipose tissues reside. Several studies have shown that either waist circumference or waist-to-hip measures are better predictors of mortality.

The new class of drugs, known as glucagon-like peptide-1 (GLP-1) receptor agonists, such as semaglutide (known by brand names Ozempic to treat diabetes and Wegovy for other purposes) and tirzepatide (Mounjaro and Zepbound), appear highly effective in reducing weight, as well as decreasing adverse health outcomes including diabetes, heart disease, and stroke. Additional benefits may include a reduction in chronic back pain, fatigue, sleep apnea, and even addictions, (e.g., drinking and smoking.)

Those who take them may be rewarded in six to 16 months with a weight loss from 15% to 20%, though they can be accompanied by some nasty side effects, such as nausea, vomiting, constipation, and fatigue. These weight-loss percentages are higher than through diet and exercise alone but do not reach the 30% achievable by bariatric surgery. So far, they have been shown to be safe.

However, at least in their current form, they need to be taken for life, as the lost weight is regained if stopped. Some studies have shown that less than one-third of those starting such medications continue after a year. And their long-term effects are not yet known, including their continued effectiveness. Their effect on muscles remains under study. Also, it is not clear to me how effective they are for those who are obese due to genetic, rather than behavioral reasons.

The potential market for these medications is huge; 1.1 billion people globally (14% of the global population) are obese. List prices for these medications are now quite high—upward of $15,000 a year. With so many who might be eligible, the total cost could be enormous. Determining whether this cost is cost-justified (and of course, cost is not everything!) involves an assessment of future associated medical and related benefits compared with alternative weight control methods involving nutrition and physical activities, although these have often proven unsuccessful.

The enthusiasm around GLP-1s should not distract us from the need for policy reform to reduce consumption of ultra-processed food and sugar-sweetened beverages. Far more can be done to increase access to affordable, nutritious food such as fresh fruits and vegetables.

Because there are so many potential users, the market is becoming increasingly competitive. For now, demand outstrips supply, even at their very high prices. Reportedly there are about 90 candidate drugs in various stages of development; I look forward to future advances. The goal is to ensure patients will be able to tolerate the medicine and find it easy to use through oral versions at a lower price.

Their high price may make it challenging for health insurers and plan sponsors to provide widespread coverage for ­other-than-extreme cases. Although health insurers have begun to offer coverage for these new drugs, insurance and health care professionals are generally taking a cautious approach.

There is no magic bullet that can fix the obesity epidemic, nor a single approach that is right for everyone. Nevertheless, along with nutritional and fitness regimens, GLP-1s can help many achieve weight health otherwise unachievable.

These drugs represent a true medical advance that can help many, yet many questions remain. Overall health will be determined based on a combination of pharmaceutical, medical, and behavioral actions.

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