Weighing the pros and cons, and dollars and cents, of the new wave of weight-loss drugs

Obesity rates in the United States have tripled since the 1980s. According to the CDC, a mind-boggling 41.9% of adults were obese as of 2020. Many adults with obesity have a higher risk of developing other health problems, such as heart disease, hypertension, joint pain, and certain types of cancer.

This is a national health crisis.

When it was discovered that new diabetes drugs induced rapid and substantial weight loss, it received quite a bit of attention from a population at such risk for obesity. But, as effective as they are, these drugs are not magic. There’s much to consider for patients, providers, and health plans.

Ozempic is the headliner

Of all the drugs being used for weight loss these days, none has gotten more attention than Ozempic. Manufactured by Novo Nordisk, Ozempic is a self-administered injectable diabetes medication in the glucagon-like peptide 1 (GLP-1) receptor agonist class. It mimics a natural substance in the body that is released when we eat and causes the body to reduce blood glucose by producing more insulin.

Despite the amount of attention it has received, Ozempic is FDA approved only for the treatment of type 2 diabetes and not obesity. However, it has been prescribed for off-label use and was found to be an effective weight-loss drug.

Not only does Ozempic boost the release of insulin, it slows the release of sugar from the liver, delays digestion in the gut, and reduces appetite, which helps people eat less.

Wegovy is… Ozempic, but more of it

Wegovy is exactly the same as Ozempic — same manufacturer, same active ingredient (semaglutide). What makes it “different” is it is administered at a higher dosage and, as a result, is more effective for weight loss than Ozempic. Unlike Ozempic, Wegovy is only FDA approved for weight loss in patients who have a body mass index (BMI) greater than 30 or those with a BMI of 27 with certain other risk factors.

Because of the perceived interchangeability of Ozempic and Wegovy, some physicians have prescribed both drugs for weight loss. This has resulted in supply shortages that impact patients who need these medications, for diabetes or for weight loss. Further contributing to this shortage is the prescribing of these medications off label to patients.

Another option, minus the injection

Novo Nordisk also manufactures Rybelsus, which is an oral semaglutide tablet approved for the treatment of type 2 diabetes. Novo Nordisk is seeking FDA approval for this drug for weight loss, but at a dosage three and a half times what is used for diabetes.

One drawback of Rybelsus, despite being a tablet instead of an injectable, is it must be taken every day, in the morning on an empty stomach, at least 30 minutes before drinking or eating anything other than water or taking any other oral medications. It’s clearly not as convenient as the once-weekly injectables, Wegovy and Ozempic. But for those with an aversion for needles, that’s a small price to pay.

How it started

In 2014, Novo Nordisk introduced the first GLP-1 agonist for weight loss, Saxenda, which contains the active ingredient liraglutide. Originally approved under the name Victoza for treatment of type 2 diabetes, Saxenda is a once-daily subcutaneous injection. It is not as convenient and has relatively inferior weight loss results when compared to Wegovy. Not surprisingly, Saxenda has not enjoyed the same recent success as its trendy competitor.

Is the latest the greatest?

Mounjaro, from manufacturer Eli Lilly, is the latest diabetes drug to get attention for off-label use in weight loss. With the active ingredient tirzepatide, studies indicate this drug is even more effective for weight loss than the semaglutide drugs.

The two-pronged effect of Mounjaro involves both the GLP-1 agonist pathway currently utilised by competitors Ozempic and Rybelsus, and a second mechanism that involves the glucose-dependent insulinotropic polypeptide (GIP) receptor, which promotes insulin secretion and regulates lipid and glucose metabolism. The net effects of these dual actions with Mounjaro have led to greater glycemic control and weight loss, which played out in head-to-head clinical trials where it outperformed semaglutide. The FDA is likely to authorise it for weight management within the year. Some industry analysts expect it to become one of the top-selling drugs of all time.

More on the way

The popularity and profitability of the medications already mentioned have ensured there is a pipeline full of potential new weight-loss drugs on the way. Approval for type 2 diabetes will once again be the likely path to seeking an approval for treating obesity.

Novo Nordisk and Eli Lilly are both conducting clinical trials right now, while Amgen and Pfizer also have drug candidates under study. Like Ozempic and Wegovy, when these gain approval as weight-loss drugs, they will most likely be under different names and dosages than those used in diabetes. This is not only for marketing purposes, but also to clearly separate their intended uses. Some payers of healthcare do not cover drugs for weight loss and the manufacturers want to make sure access to their treatments for diabetes are not compromised.

Side effects may include…

The effectiveness of these drugs is undeniable, with average weight reductions of around 15%. However, they are not without side effects, such as nausea, vomiting, diarrhea, dehydration, fatigue, and a range of other gastrointestinal issues.

In clinical trials, anywhere from 15% to 45% of patients experienced some sort of gastrointestinal side effect. And as the dosage increased, so did the effects. That’s not a small number. However, inadvertently and quite uncomfortably, those side effects may actually contribute to the success of the drugs.

The cost of obesity

Some of the figures associated with the effects of obesity are staggering. According to the CDC, obesity costs the healthcare system $173 billion a year.

And, according to a 2018 report by The Milken Institute, obesity-related complications resulted in $1.39 trillion worth of direct medical treatments and indirect productivity losses due to chronic diseases. Those conditions include type 2 diabetes, hypertension, osteoarthritis, coronary heart disease, stroke, and chronic back pain, among others.

These diabetes/weight-loss medications can be quite costly — roughly $900 to $1,600 a month per patient. But what is the eventual cost down the line for the entire healthcare system if obesity is left untreated? Much more than the sticker price of the drugs.

Medicare and most Medicaid programmes, which have historically set the precedent for commercial plans, do not cover anti-obesity medications. However, a proposed Senate bill entitled the Treat and Reduce Obesity Act would extend Medicare Part D coverage to include these drugs. This could influence commercial plans to adjust their approach.

When it comes to private insurers, weight-loss drugs have traditionally been viewed as no less cosmetic than a Botox injection or mole removal. This is why they’re commonly excluded from health plans. And that trend continues. Only about 25%t provide coverage after prior authorisation — and another 10-15% without it.

With the increasing popularity of these drugs, plan sponsors face mounting pressure to extend coverage. And as figures in the billions and trillions that stem directly from not addressing obesity at an early stage continue to emerge, it may also accelerate the rate of change.