Wegovy vs. Zepbound - Part 1
Not Just a White Pill - Clinical Study Series
I am a licensed pharmacist and practiced pharmacy in a retail setting. I am also a clinical scientist developing clinical trials for new innovative pipeline products.
From non-clinical, Phase I clinical to Phase III clinical and beyond, the drug development starts with the product label in mind. I want to introduce how clinical studies are designed and how the clinical study information on product labels impacts patients’ lives using Wegovy and Zepbound as examples.
Why is BMI = 27 kg/m2 and 30 kg/m2?
The FDA guideline for weight management defines overweight as 25 - 29.9 kg/m2 and obesity is defined as 30 kg/m2 or above in adults. So, if the pharma/biotech wants to study the weight loss effect in obese patients, the criteria is greater than or equal to 30 kg/m2.
For, overweight criteria, the FDA needed to define what they would consider their acceptable starting point for overweight BMI. In the guideline, there is the following statement:
“we believe that individuals with BMIs greater than or equal to 30 kg/m2 or greater than or equal to 27 kg/m2 ……. to justify inclusion in studies of investigational weight-management products.”
The answer to why BMI starts with 27 kg/m2 for overweight and 30 kg/m2 for obese patients, is due to FDA guidance and all weight management products must follow this FDA guidance of weight management. Hence, both Wegovy and Zepbound identified overweight and obese as 27 kg/m2 and 30 kg/m2 respectively.
Was it necessary to include diet and exercise?
The short answer is yes but there is little twist. The FDA guideline mentions the importance of lifestyle modification of diet, exercise, and other behaviors to manage body weight.
“Lifestyle modification, consisting of changes in patterns of dietary intake, exercise, and other behaviors, is considered the cornerstone of overweight and obesity management.”
However, the FDA does acknowledge the risk of any agents (drug or biologics) and adds further statement:
“the use of a weight management product should be contemplated only after a sufficient trial of lifestyle modification has failed and the risks of excess adiposity and the anticipated benefits of weight loss are expected to outweigh the known and unknown risks of treatment with a particular weight management product.”
Both Wegovy and Zepbound trials have inclusion criteria where eligible patients must have at least one failed attempt at managing weight by implementing lifestyle modification. Therefore, all overweight and obese patients had failed at least once in modifying their lifestyle.
What about 68 weeks or 72 weeks study duration?
The FDA guidance does not specify how long the weight management products need to be studied to demonstrate their efficacy. However, the FDA generally accepts that the product needs to show over the course of at least 1 year before the product can be considered effective for weight management.
Please note that 68-week or 72-week durations are chosen to show weight management efficacy.
So, is 68-week weight management worse than 72-week weight management? It is hard to say, but with Zepbound having studied 4 more weeks than Wegovy, I would use this as a competitive advantage for Zepbound's marketing strategy.
Greater than or equal to 5 percent weight loss?
Both Wegovy and Zepbound have two main factors to show the effectiveness of the products and you can find them on their respective websites.
Percentage change in body weight over time from baseline to end of study.
Percentage of patients who achieved greater than or equal to 5 % weight loss at the end of the study.
The first factor is what most people are interested in, but there is a rationale for having a second factor.
“long-term weight loss greater than or equal to 5 percent following the diet, exercise, and in some cases, drug treatment, is associated with improvement in various metabolic and cardiovascular risk factors”
Above FDA’s rationale for 5 percent or greater in weight loss is to decrease the co-morbid risk factors in overweight and obese patients. The improvement in various metabolic and cardiovascular (heart disease) risk factors leads to a decrease in healthcare costs, an increase in economic output (productivity), and most importantly, higher quality of life.
Takeaway
All clinical studies are based on the clinical study guidance the health regulatory agencies (FDA) provide. Every country has different regulatory guidances and must comply to get a chance for drugs to be approved.
Clinical scientists work closely with the regulatory affairs team to design clinical studies that comply with regulations.
Part 1 was an introduction and the Part 2 will explain how all these affect patients in accessing the medication. For a preview, get ready to get frustrated with insurance, and please don’t let your anger out to your pharmacists.
Thank you for your time.
-ProoSt!
Disclaimer: This newsletter is intended for educational purposes only. Always consult with your healthcare provider to choose the best medication therapy for the optimal outcome that benefits you. If you want me to provide an in-depth analysis, feel free to connect with me.