COMMENTARY

Will Wegovy Be of Little Use for Weight Loss?

Akshay B. Jain, MD

Disclosures

August 12, 2021

For as long as I have been practicing obesity medicine, I have heard from colleagues that they don't prefer using anti-obesity medications because they are "just not effective." Much of this might change with the STEP studies, data from which were shared at this year's American Diabetes Association (ADA) Scientific Sessions.

All of the studies have been published, the data celebrated and eagerly discussed. Yet I can't help but wonder: Will these results be enough? Or might there be greater hurdles we must face before widespread uptake of anti-obesity medications?

Groundbreaking Results

In STEP 1, weight loss with semaglutide in patients with prediabetes was 14%, compared with 2% in the placebo group. The percentage of patients with prediabetes changed from 45% at baseline to 9% with semaglutide, and only 0.2% went on to develop overt diabetes.

 

Looking at glucose metabolism, 84% of those who had prediabetes at the time of enrollment became normoglycemic. This was essentially driven by weight loss, as over 79% of patients with weight loss > 5% in the semaglutide group became normoglycemic. STEP 1 was the first phase 3 study to show that one third of patients on semaglutide 2.4 mg/wk lost more than 20% body weight, compared with 2% in the placebo group.

In STEP 2, patients with type 2 diabetes had a decrease in A1c by 1.6% with semaglutide 2.4 mg, compared with 1.5% with semaglutide 1.0 mg and 0.4% with placebo. Similar to STEP 1, the improvement in glycemic control was essentially driven by weight loss.

Subset data demonstrated that a staggering 45% of patients in the semaglutide 2.4 mg group were able to achieve the composite endpoint of weight loss ≥ 10% and A1c < 7% (compared with 7% of patients in the placebo group), and a remarkable 26% achieved the composite endpoint of weight loss ≥ 15% and A1c < 7% (compared with 3% of patients in the placebo group).

Furthermore, there was a significant reduction in waist circumference with semaglutide vs placebo, which is important because waist circumference is a marker of visceral adiposity.

What Does This Mean for Our Patients?

Weight loss with the 2.4-mg dose of semaglutide is above and beyond what we have already seen with the previously approved 1.0-mg dose in patients with type 2 diabetes. But STEP 2 showed that A1c-lowering was very similar between the two doses. This is an important discovery. For patients with uncontrolled type 2 diabetes on semaglutide 1.0 mg but at target body weight, there would be little improvement in glycemic control by increasing the dose to 2.4 mg.

However, most patients with type 2 diabetes are battling with overweight or obesity, and the weight loss and reduction in waist circumference seen with this medication are extraordinary, making it a useful adjunct to lifestyle modifications and other antidiabetic medications.

Although not a diabetes prevention trial in the strict sense of the term, STEP 1 had a robust number of participants with prediabetes. It was impressive to see that nearly twice as many patients in the semaglutide group were able to achieve normoglycemia compared with the placebo group, an effect driven primarily by weight loss. This will significantly drive down the risk that millions of Americans with prediabetes will develop overt diabetes.

Individuals with overweight or obesity are often unable to sustain intensive behavioral therapy or low-calorie diets. Results from STEP 1 and STEP 3 suggest that semaglutide combined with basic lifestyle and dietary counseling achieves similar results to those seen with semaglutide and intensive behavioral therapy. This will help increase the probability of adherence because patients often find low-calorie diets with intensive behavioral therapy difficult to conform to in the long run.

Adherence to anti-obesity medications is of paramount importance, as suggested by the results of STEP 4, which demonstrated significant rebound weight gain when the medication was discontinued.

Finally, it's important to realize that some people may not experience clinically significant weight loss > 5%. In the STEP studies, 7%-13% of patients did not reach this threshold. For these patients, reconsider pharmacotherapy rather than continuing the same medication.

We now have a therapy where one third of users can actually achieve weight loss > 20%, a target that was hitherto unthinkable with nonsurgical measures. This is without a doubt a new frontier in our fight against obesity and should be heralded as such. Healthcare professionals need to update their arsenals, and perhaps a medication with such significant efficacy might help us overcome the stigma and resistance to prescribing anti-obesity medications.

But Wait… There's Another, Greater Hurdle

In a world where obesity is not yet being given due recognition as a disease, the US Food and Drug Administration's approval of Wegovy is no doubt an important step forward. But I feel that this is not enough.

Coming in at a median retail price of over $1300 per month, this drug immediately becomes inaccessible for the vast majority of individuals who need it most. With many insurers not covering previously available obesity drugs, the fate of millions of Americans unfortunately remains unchanged despite having a stellar new medication available. For those without insurance, using a medication this expensive is virtually unthinkable.

It is time that patient advocacy groups, physician organizations, and all avenues of media alike strenuously urge our representatives to take action to make anti-obesity medications more accessible. The health of countless individuals could worsen significantly if this opportunity is lost. The last thing we need is people with obesity starting this medication and losing weight, only to ration — or worse, discontinue — the medication owing to unaffordability, and then watch helplessly as the weight is regained.

My father, a general practitioner for over 48 years, once told me, "You may have the best medication in the world at your disposal, but your prescription is no more than a useless piece of paper if there isn't proper access available for the medication." So, it's time to ask ourselves: What will we do to ensure that prescriptions for medications like Wegovy can go beyond existing as mere pieces of paper?

Akshay B. Jain, MD, is a clinical endocrinologist who has practiced in three countries, focusing on mitigating the complications of diabetes and obesity. He is fluent in six languages and has spoken at more than 500 programs internationally.

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