Ozempic has revolutionized obesity treatment, but it’s just the beginning. New experimental drugs are on the horizon, promising even greater effectiveness in weight loss. A recent review published in the Annals of Internal Medicine highlights the potential of these emerging treatments.
Researchers at McGill University analyzed clinical trial data for GLP-1 drugs like semaglutide (the active ingredient in Ozempic and Wegovy). Their findings reaffirmed the safety and efficacy of current medications while emphasizing the potential of newer compounds. These include retatrutide, which has demonstrated impressive results in trials, helping individuals lose over 20% of their initial body weight.
Semaglutide, a synthetic, long-lasting version of the hormone GLP-1, regulates hunger and insulin production. Developed by Novo Nordisk, it was first approved for type 2 diabetes (Ozempic in 2017) and later for obesity (Wegovy in 2021). While not the first GLP-1 drug, semaglutide has significantly impacted obesity treatment, helping people lose 10% to 15% of their weight in studies – considerably more than diet and exercise alone, and exceeding the results of older GLP-1 medications.
Emerging Competitors and Triple-Agonist Therapies
Semaglutide faces competition from Eli Lilly’s tirzepatide, which mimics both GLP-1 and GIP (another hunger-related hormone). This powerful combination has led to weight loss of up to 20% in clinical trials, surpassing semaglutide’s efficacy. Numerous other obesity treatments are in development, some already in human trials, poised to outshine even tirzepatide.
The McGill researchers examined data from 26 randomized clinical trials involving single-agent GLP-1 drugs, double agonists like tirzepatide, and triple-agonist drugs like retatrutide. Retatrutide combines synthetic versions of GLP-1, GIP, and glucagon, targeting three hunger-related hormones. The trials focused on individuals with obesity but without type 2 diabetes.
As anticipated, approved drugs proved safe and effective, with tirzepatide showing the best results (up to 17% body weight reduction after 72 weeks). However, retatrutide demonstrated even greater efficacy in a shorter timeframe, with participants losing up to 22% of their body weight after just 48 weeks.
Retatrutide and the Future of Weight Loss
The researchers highlighted retatrutide, tirzepatide, and semaglutide as the top performers in weight reduction among the 12 GLP-1 drugs analyzed. Retatrutide, currently in phase 3 trials by Eli Lilly, is expected to complete testing by 2026.
Other promising drugs are also emerging. Early trial results for amycretin (Novo Nordisk) suggest it may outperform both semaglutide and tirzepatide. Companies like Boehringer Ingelheim and Zealand Pharma are developing their own Ozempic competitors, such as the dual agonist survodutide. The anticipation for new treatments is high, as evidenced by Novo Nordisk’s stock dip when their drug candidate CagriSema (semaglutide combined with cagrilintide) achieved 22% weight loss in a recent trial, falling short of the projected 25%.
Challenges and Considerations
These drugs are not without drawbacks. Common side effects include gastrointestinal issues like diarrhea and vomiting. Rare but serious complications, such as gastroparesis (stomach paralysis), have also been reported. Cost remains a significant concern, with semaglutide and tirzepatide often priced around $1,000 per month without insurance, which is frequently not covered. This high cost and increasing demand have led to a grey and black market for cheaper, but potentially unsafe, compounded and counterfeit versions.
Looking Ahead
Some experts believe that the arrival of more GLP-1-related drugs will address some of these challenges, particularly cost and insurance coverage. While the future impact remains uncertain, the influx of new obesity treatments is poised to challenge the current dominance of semaglutide and tirzepatide.
The development of these new medications offers hope for individuals struggling with obesity, providing potentially more effective and accessible treatment options. The coming years promise exciting advancements in the field of obesity management.
