Research in the field of weight loss drugs is progressing at a faster pace. Drugs that mimic GLP-1 have been introduced to the market for treating weight issues and diabetes, but their side effects, which primarily affect the digestive system, cause about 40% of individuals who start them to stop using them within a year.
New Drugs with Fewer Side Effects
At the annual meeting of the European Association for the Study of Diabetes (EASD) in Milan, researchers from pharmaceutical companies producing popular weight loss drugs presented promising results from studies of new injectable drugs that may have fewer side effects.
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Amylins are a group of peptide hormones that similarly act to GLP-1, inhibiting appetite signals in the brain and aiding gastric emptying. Amylins target various receptors in cells, and their effect may complement the action of GLP-1 and other drugs in their hormonal group (called incretins). However, unlike incretins, amylins appear to cause fewer severe side effects such as nausea, vomiting, and stomach cramps.
Results of CagriSema Drug Trials
Researchers from Novo, which produces the drugs Wegovy and Ozempic, announced that their experimental amylin-based combination called CagriSema, administered as a weekly injection, has helped overweight or obese individuals lose 22.4% of their initial weight over a year compared to those who received a placebo. The company also emphasized brain fMRI studies showing that CagriSema alters brain responses to food and may reduce food appeal.
In individuals with type 2 diabetes, this drug reduced harmful fat in the liver and pancreas, an early and promising sign that it may contribute to health benefits beyond weight loss. CagriSema is a combination of semaglutide—the active ingredient in Wegovy and Ozempic—with cagrilintide, an amylin analog that mimics the hormone produced in the pancreas that regulates feelings of fullness.
Martin Holst Lange, Executive Vice President and Chief Scientific Officer of Novo, noted that the company also has an early-stage study on individuals with type 2 diabetes showing that CagriSema can reduce nerve pain. He said, "This is incredibly exciting because we are demonstrating that in addition to weight loss and blood sugar control, CagriSema can further assist individuals in their daily lives."
Research on Combination Drugs
Researchers from Eli Lilly, which produces the drug Zepbound (tirzepatide), presented a report on the experimental combination drug EloraTZP, which includes the amylin analog eloralintide and tirzepatide. This drug has helped overweight or obese individuals, as well as those with type 2 diabetes, lose 23% of their initial weight compared to 14.8% in individuals who only received tirzepatide. This weekly injectable drug has also helped individuals reduce A1C, a diabetes measure, more than taking tirzepatide or amylin alone.
Zealand Pharma also published results from a study that appeared in The Lancet on September 29. The company's amylin-based combination, called pramlintide, resulted in an average weight loss of 10% for individuals who are overweight or obese but do not have diabetes. In this study, individuals receiving even the highest doses of the experimental drug reported similar side effects to those receiving a placebo.
Due to their efficacy and favorable side effect profile, amylin-based drugs may one day become the first option for individuals seeking reasonable weight loss without the unpleasant side effects associated with GLP-1 drug class. Dr. Timothy Garvey, a professor of nutrition sciences and senior scientist at the Nutrition Obesity Research Center at the University of Alabama, stated that while amylins still cause some nausea, the rate is less than half of what is typically observed in GLP-1 trials. He added, "Not everyone needs to lose significant weight, so amylin drugs can be a pleasant option for them."
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