Has obesity met its match?

Even if powerful drugs can help, lifestyle interventions are key

A new weight loss drug was recently approved by the FDA. The new drug joins a family of new-ish drugs that act like naturally occurring hormones that besides regulating glucose and insulin also help control appetite.

Previous weight loss drugs brought about high hopes for an easy (or at least easier) fix to what’s a very difficult problem plaguing the majority of people in the US. Each promising drug came tumbling down with either disappointing weight loss results – especially in the long-term – or unreasonable risks and side effects. 

Amphetamines have been used for weight loss from the 1930s, they really took off after World War II and were prescribed in abandon, leading to much abuse, reminiscent of our current opioid crisis (amphetamines are less deadly, but side effects include addiction, hypertension and psychosis). Phen-phen and Redux were popular in the 90s, only to be removed from the market before the century’s end over links with heart-valve damage and pulmonary hypertension. Ephedra, a popular weight loss dietary supplement, was banned in 2004 after strokes and other cardiovascular events appeared to increase among users.

The new class of drugs are glucagon-like peptide 1 (GLP-1) analogs, which mimic our naturally occurring GLP-1 hormone. Hormones are secreted into the blood system, and through it, distributed all over the body, enacting their effect in multiple organs and systems. GLP-1 analogs were developed for the treatment of type 2 diabetes – they stimulate insulin secretion in the presence of glucose and reduce the amount of sugars secreted from liver storage. People using these GLP-1 analogs, many of them also with overweight and obesity, noticed better than expected weight loss results. The drugs may help with weight loss through several mechanisms: direct effects on the brain’s appetite control, as well as slowing the emptying of the stomach. You may have noticed ads for the drug Trulicity, another GLP-1 agonist – it’s widely advertised to consumers for the treatment of type 2 diabetes – claiming that “you may lose up to 10 pounds.” Trulicity wasn’t designed or approved as a weight loss drug, and is not prescribed to people who don’t have diabetes.

But the incidental drop in pounds led to testing GLP-1 analog formulations for weight-loss itself. Semaglutide, made by Novo Nordisk, is a type 2 diabetes drug. In a clinical trial recently published in the New England Journal of Medicine involving almost 2000 adults with obesity or overweight with one or more weight-related coexisting conditions, who do not have diabetes, the drug was tested against a placebo for 68 weeks. Both the treatment and the placebo groups were given lifestyle coaching regarding diet and physical activity. 

The difference between the treatment arm and the control arm in weight loss results is stark. The people treated with semaglutide lost on average almost 15% body weight, compared with the 2.4% for those on the placebo, more than a 12% difference. A third of the people on the drug lost 20 percent body weight, which is in bariatric surgery weight loss territory. The average weight loss at 68 weeks was more than 33 pounds. The authors conclude that semaglutide in addition to a reduced calorie diet can lead to sustained and significant weight loss.

Not a (magic) pill

The drug, semaglutide, or in its commercial name Wegovy, isn’t a pill, and cannot be ingested – it’s injected one a week. It seems that treatment will need to be ongoing. It’s also going to be expensive – the price isn’t yet published, but is estimated at $1,300 a month.

The trial lasted longer than a year, which may seem like ample time; weight maintenance after weight loss is a long game, however. There are multiple powerful mechanisms that seem to kick in and nudge our bodies to regain lost weight, even after keeping it off for extended times – appetite and eating behavior are very well guarded mechanisms which enabled our ancient ancestors to survive a food-scarce past. Will the drug remain as effective over time? Even longer studies are needed when it comes to weight loss.

Not without risk

This drug, like other GLP-1 analogs, can have side effects. Common ones are gastrointestinal, and include nausea, diarrhea and abdominal pain. More severe side effects are rare, but include pancreatitis, kidney, thyroid and gallbladder disease as well as low blood sugar.

Eating well is as crucial as ever

People who have significant extra weight and its complications (prediabetes, hypertension, sleep apnea etc.) are advised to lose 10-15% of their weight, but even when they achieve that weight loss keeping the weight off remains a daunting challenge. There’s another GLP-1 agonist drug that's already approved for weight loss, Liraglutide, which is injected daily. The approval of another drug, one that’s more easy to administer, is welcome news – we need all the tools we can get. 

But even with powerful drugs, lifestyle interventions remain key.

All the trial participants relied on a low-calorie diet and an exercise regimen to lose weight; the drug was added on that backbone. All weight loss medications are just part of the weight loss plan that always centers on the food and diet habits, and on physical activity.

And regardless of weight status, eating well reduces the risk of many of the chronic diseases associated with obesity – independent of weight.

I suspect that there will never be an easy way out from actually practicing a healthy lifestyle in order to maximize wellness.

Dr. Ayala