The landscape of obesity treatment is on the cusp of a significant transformation, with a new generation of drugs poised to enter the market. Following the groundbreaking success of Novo Nordisk’s Ozempic and Wegovy, and Eli Lilly’s Mounjaro and Zepbound, pharmaceutical companies are engaged in a vigorous race to develop the next generation of GLP-1 drugs. These experimental medications hold the promise of not only addressing diabetes and weight loss but also enhancing liver and heart function while minimizing common side effects like muscle loss associated with existing treatments.
The Rise of GLP-1 Drugs
The American Diabetes Association (ADA) conference in Orlando, Florida, showcased the extensive research and development in this field, with data presented on 27 GLP-1 drugs in development. Dr. Marlon Pragnell, ADA’s vice president of research and science, noted the excitement surrounding the multitude of drug candidates, spanning from early-stage preclinical studies to late-stage clinical trials.
Dr. Christopher McGowan, a gastroenterologist who runs a weight loss clinic in Cary, North Carolina, emphasized the unprecedented acceleration in the development of GLP drugs, marking the arrival of the GLP era. While existing drugs have proven highly effective, the need for more affordable options with fewer side effects remains a priority.
Beyond GLP-1: Exploring Amylin
The focus isn't solely on GLP-1 drugs. Zealand Pharma, a Denmark-based biotech firm, unveiled data on its experimental weight loss drug, petrelintide. This weekly injectable medication stands out by mimicking the hormone amylin, crucial for blood sugar control. The hope is that patients will experience fewer side effects like nausea, commonly linked to GLP-1 drugs such as Wegovy and Zepbound. Data showed that a high dose of petrelintide helped reduce body weight by an average of 8.6% at 16 weeks.
The Role of Glucagon
Glucagon, another hormone, is gaining attention in the development of weight loss drugs. While GLP-1 medications work by slowing down the passage of food through the stomach, glucagon is a key blood-sugar-regulating hormone that can mimic the effects of exercise.
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Altimmune, a Maryland-based biotech firm, presented data on pemvidutide, a drug containing both GLP-1 and glucagon. In a phase 2 trial involving adults with obesity or who were overweight with at least one weight-related comorbidity, patients receiving the highest dose of pemvidutide experienced an average weight loss of 15.6% after 48 weeks, compared to 2.2% with a placebo.
Dr. Scott Harris, Altimmune’s chief medical officer, highlighted the drug's potential to provide health benefits to the liver and heart, as well as preserve lean body mass. Vipin Garg, Altimmune President and CEO, emphasized that their approach adds another component beyond appetite suppression.
The Competitive Landscape
Eli Lilly, the maker of Zepbound and Mounjaro, is also actively developing additional GLP-1 drugs. Retatrutide, an injectable drug combining GLP-1, glucagon, and GIP, has shown promising results in earlier trials, with patients experiencing an average weight loss of about 24% of their body weight. New findings showed the weekly medication also significantly reduced blood sugar levels in people with Type 2 diabetes. Mazdutide, another experimental drug from Lilly being developed in China by Innovent Biologics, combines GLP-1 and glucagon and has demonstrated a 14.4% average body weight reduction in overweight or obese adults after 48 weeks.
Addressing Metabolic Conditions
Boehringer Ingelheim's survodutide, which utilizes both GLP-1 and glucagon, has shown promise in improving metabolic conditions. In a phase 2 trial, survodutide led to a weight loss of 19% at 46 weeks and showed improvement in MASH in 83% of participants. Dr. Waheed Jamal, Boehringer Ingelheim’s corporate vice president and head of cardiometabolic medicine, emphasized the drug's potential to make a meaningful difference in cardiovascular, renal, and metabolic conditions.
Novel Approaches to Weight Loss
Novo Nordisk presented findings on amycretin, a daily weight loss pill that demonstrated a weight loss of up to 13% after three months in a Phase 1 clinical trial. Dr. Christopher McGowan noted that the weight loss rate was roughly double that seen with current GLP-1 agonists, approaching surgical-level outcomes. Amycretin works similarly to semaglutide but also imitates amylin, promoting a feeling of fullness.
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Amgen's MariTide, a monthly injectable drug, helped people lose about 20% of their body weight in a phase 2 clinical trial. MariTide differs from other GLP-1 drugs by including a monoclonal antibody, extending its duration in the body. The trial results, published in the New England Journal of Medicine, showed significant weight loss in both people with Type 2 diabetes and those with obesity alone.
Head-to-Head Comparisons
In a head-to-head clinical trial funded by Lilly, Zepbound demonstrated greater weight loss than Wegovy. Patients on Zepbound lost an average of 20.2% of their body weight after 72 weeks, compared to 13.7% for those on Wegovy. While both drugs are highly effective, Zepbound provided 47% more weight loss than Wegovy, according to Lilly.
Challenges and Considerations
Despite the excitement surrounding these new drugs, challenges remain. The high cost of existing medications like Wegovy and Zepbound, which can exceed $1,000 a month, poses a significant barrier to access. Increased competition among drugmakers could potentially drive down prices over time, making these treatments more accessible to patients.
Individual responses to treatments can also vary. Dr. Fatima Cody Stanford noted that different GLP-1 drugs may have varying levels of efficacy and potency, with some patients responding better to one drug than another.
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