Turn the page of obesity therapy – addressing tolerance and delivery

Weight management remains a popular topic in our society. This is not surprising, as reports suggest that obesity affects nearly 43% of adults in the United States alone. Obesity is more than just a certain amount – it is the main driver of chronic diseases such as diabetes, cardiovascular disease, sleep apnea and even some cancers. Physicians and hospitals see a direct correlation between the percentage of obese individuals and their visit to the emergency room.

Although many people have changed their weight management through diet, exercise and lifestyle, some still need other treatments to lose weight. Studies have found that even moderate weight loss, 5-10% of body weight can lead to meaningful health improvements.

It's obvious why many people think that GLP-1 drugs are a whole new option for the treatment of obesity, but in fact, they've actually been around for over a decade. The FDA approved Saxenda (Liraglutide) as the first GLP-1 to lose weight in 2014. Wegovy (Semaglutide) didn't get approval from the FDA until 2021, and the same instruction was not obtained until 2021.

GLP-1 on the market is a weekly subcutaneous injection that suppresses appetite and creates a pathway of treatment that has not existed before. They have made significant progress in the field of obesity and are able to lose weight quickly in individuals. Nevertheless, challenges have become increasingly apparent over the past few years, including gastrointestinal (GI) problems that have created enough barriers for users to participate in daily activities in their lives.

Tolerance remains the biggest challenge for GLP-1, as many patients suffer from adverse events and discomfort. Due to GI and GI-related issues, about 20-30% of patients treated with GLP-1 stopped using and dropped out of school after one year, with these side effects and financial reasons considered. Although these medications may lose weight, the quality of life becomes questionable.

As the obesity epidemic continues to increase, we are at a turning point in public health. It is clear that the latest scientific breakthroughs need to face the challenge of solving the obesity crisis. Biotech and pharmaceutical companies are turning to alternative pathways to address tolerance.

A new wave of obesity treatment

We are beginning to see the transition within the industry, and more research and development will involve GLP-1/glucagon double-acting agonist weight loss treatments are investigated. When making switches, this concept is similar to the GLP-1 and is nothing new. The development of this concept has been happening since the mid-2010s. A company is able to enter Phase 2 of type 2 diabetes before it reaches its end. These efforts are not wasted, as they show scientists and researchers that the ratio between GLP-1 and glucagon activity is crucial to success. It works because GLP-1 lowers glucose, and glucagon tends to increase glucose. Adding too many ones will change the balance and cancel the other.

We see multiple ratios being tested throughout the industry. Preclinical testing shows that some companies are investigating a fully balanced 1:1 ratio. Altimmune is a major example of such a use of Pemvidutide using a 1:1 ratio, and it is obvious that there is no obvious glucose control. On the other hand, some companies are testing heavier GLP-1 weights, such as 6:1 or 8:1, which have not been successfully provided for glucose reduction in clinical testing. The industry realizes that more GLP-1 itself does not mean better results. Find the right balance to produce better results.

Delivery method

Although progress is being made in innovation to address tolerance challenges, significant progress has also been made in the delivery of treatments. As mentioned earlier, the current GLP-1 therapy on the market is a weekly subcutaneous injection. Biotech and pharmaceutical companies realize that not only weekly injections are bad, but they are not the most convenient.

One delivery method currently being explored is long-acting injections. These monthly injections can improve patient compliance, but injections must also show sustained efficacy and tolerance. If the formula works in the absence of adverse events, this delivery method will be a significant advance in the obesity market.

Another delivery method being explored and becoming a more popular option is the oral version of the oral GLP-1 drug. If successful, this approach would be a game-changing patient convenience, but a lot of things are going to happen. Turning injected peptides into effective oral formulations is challenging and a daunting task. However, many biotechnology and medicines have faced the challenge and we may see the first oral GLP-1 drug approved by the FDA.

Completely harmonious

GLP-1 has made great progress in the obesity market. Research and development undoubtedly paves the way for this new era of weight loss therapy. As scientists and researchers figured out the right balance between GLP-1 and glucagon-better methods of delivery of drugs, we began turning pages for many people with obesity. Making treatments more tolerant, cost-effective and accessible will allow individuals to lose weight without the burden of serious side effects, ultimately allowing them to maintain a healthier lifestyle.

Photo: Peter Dazeley, Getty Images

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