The quest for effective and sustainable weight loss solutions has led to significant advancements in medical research. This article explores the latest developments in weight loss treatments, focusing on novel drug therapies that aim to reduce body weight and improve metabolic health without the adverse side effects often associated with traditional methods. We will delve into the mechanisms of action, clinical trial results, and potential benefits and drawbacks of these promising new approaches.
The Promise of New Drug Therapies
For individuals struggling with obesity or overweight, the prospect of a medication that can facilitate significant and lasting weight loss is incredibly appealing. While lifestyle interventions like diet and exercise remain crucial, they often prove insufficient for achieving and maintaining a healthy weight. This is where new drug therapies come into play, offering a potentially more effective and convenient means of managing weight.
Orforglipron: A Once-Daily Pill for Weight Loss
One of the most promising developments in the field is orforglipron, a once-daily pill manufactured by Eli Lilly. This drug belongs to a class of medications called GLP-1 receptor agonists, which work by lowering blood sugar levels, slowing down digestion, and reducing appetite. Orforglipron targets the same GLP-1 receptors as injectable weight loss drugs like Mounjaro and Wegovy, but its oral form offers several advantages in terms of storage, distribution, administration, and cost.
In a clinical trial involving 3,127 adults with obesity (BMI of 30 or over), one in five participants who took orforglipron for 72 weeks experienced a weight loss of 20% or more. The study participants were from the US, China, Brazil, India, Japan, South Korea, Spain, Slovakia and Taiwan. The average weight loss ranged from 7.5% for those taking the lowest dose (6mg daily) to 11.2% for those taking the highest dose (36mg). Additionally, a significant percentage of patients on the highest doses achieved substantial weight reductions: 54.6% had a reduction of 10% or more, 36% had a reduction of 15% or more, and 18.4% had a reduction of 20% or more.
Besides weight loss, orforglipron also led to improvements in other health metrics, such as blood pressure, waist circumference, and cholesterol levels. The most common side effects reported were mild to moderate gastrointestinal issues, consistent with other GLP-1 receptor agonists.
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While orforglipron is not yet approved by regulatory bodies like the FDA, its potential to expand access to obesity interventions is significant, particularly for individuals who may be excluded from injectable medications due to cost or accessibility issues.
ATR-258: A Novel Approach to Fat Burning
Another experimental treatment, currently known as ATR-258, offers a different approach to weight loss. This drug, developed by Atrogi AB, aims to trigger metabolism in the muscles, specifically activating them to burn more fat. This mechanism of action differs from GLP-1 injections, which primarily affect hunger signals between the gut and the brain.
In initial human trials conducted in Sweden, ATR-258 demonstrated the ability to burn fat while preserving muscle mass. This is a significant advantage over some weight loss injections, such as Mounjaro and Wegovy, which have been associated with muscle loss, leaving patients feeling weaker. By preserving muscle mass, ATR-258 has the potential to promote healthier weight loss and improve overall body composition.
ATR-258 is based on a type of β2 (beta) agonist, a substance commonly used to treat asthma. However, these drugs can cause side effects like increased heart rate or tremors. Researchers have engineered the molecule to have a positive effect on the muscles without overstimulating the heart.
The researchers behind the study said that this drug represents a completely new type of treatment and has the potential to be of great importance for patients with type 2 diabetes and obesity. Their substance appears to promote healthy weight loss and, in addition, patients do not have to take injections.
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The next step for researchers is a clinical study planned by Atrogi AB, the company developing the treatment.
GLP-1 Injections: A Powerful Tool with Drawbacks
GLP-1 injections, such as Ozempic and Wegovy, have gained considerable attention for their effectiveness in promoting weight loss. These injections work by mimicking the natural hormone that regulates blood sugar, appetite, and digestion. While they can lead to significant weight reduction, they often come with side effects such as loss of appetite, reduced muscle mass, and gastrointestinal problems.
These injections affect the hunger signals between the gut and the brain, but can often cause a loss of appetite, reduced muscle mass and gastrointestinal problems - leaving people feeling weaker or saggy.
The Importance of Muscle Mass
Muscle mass plays a crucial role in both type 2 diabetes and obesity, and is directly correlated with life expectancy. Therefore, preserving muscle mass during weight loss is essential for maintaining metabolic health and overall well-being.
The Challenge of Sustained Weight Loss
While the initial weight loss achieved with these new therapies is promising, the real challenge lies in maintaining that loss over the long term. Studies have shown that weight regain is a common phenomenon, with many individuals regaining a significant portion of their initial weight loss within a few years.
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The SURMOUNT-4 study, for example, found that adults with obesity or overweight who took the dual GLP-1R-GIP agonist tirzepatide experienced an average weight loss of over 20%. However, after stopping treatment, participants regained an average of 14% of their weight within a year, compared to additional weight reductions of around 5% for those who continued treatment.
These results suggest that sustained weight loss may require continued pharmacotherapy, raising questions about the long-term safety and efficacy of these drugs.
The Risks of Sarcopenic Obesity
Another concern associated with weight loss, whether through pharmacological or lifestyle interventions, is the potential loss of lean muscle mass. Weight regain, on the other hand, is almost entirely fat. This cycle of weight loss and regain can lead to sarcopenic obesity, a condition characterized by low muscle mass and high body fat.
Sarcopenic obesity is commonly associated with older age and conditions like metabolic-dysfunction-associated steatotic liver disease and cirrhosis. It poses an additional threat to the health and well-being of people already trying to lose weight.
Preserving Muscle Mass During Weight Loss
Efforts to preserve lean muscle mass during weight loss are crucial for preventing sarcopenic obesity. Resistance training and protein supplementation have shown promise in maintaining muscle mass and integrity in individuals undergoing weight loss treatment.
The Long-Term Implications of New Therapies
While new-generation incretin-based therapies offer powerful tools for combating the global obesity epidemic, it is important to approach them with caution. The long-term safety profiles of these drugs have not yet been fully established, particularly in younger populations. Additionally, the question of whether these drugs maintain their efficacy over decades of treatment remains unanswered.
A Holistic Approach to Weight Management
Pharmacotherapy-mediated weight loss should not be viewed as a "silver bullet" for better health. A holistic approach that incorporates lifestyle interventions, such as diet modification, exercise, and behavioral therapy, is essential for achieving and maintaining long-term weight loss success.