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Ozempic, Wegovy and Mounjaro are turning out to be some of the most successful drugs ever churned out by pharmaceutical companies. That’s because when it comes to treating type 2 diabetes and causing weight loss, they really do work. Sales are set to soar to even greater heights because researchers are discovering that these drugs which mimic the action of certain hormones produced in the body, may produce other benefits as well. Reductions in the risk of heart, kidney and liver disease are being observed, as well reduced blood pressure and arthritic pain. Add to this a decline in addictive behaviours such as heavy alcohol drinking, opioid use and gambling, and a reduction in the risk of Alzheimer’s disease. No surprise then that the pharmaceutical industry is driven to come up with even better versions of these drugs. Novo Nordisk, the company that produces Ozempic and Wegovy, is hoping that its experimental drug, amycretin, will be the next blockbuster. While semaglutide, the active ingredient in Ozempic and Wegovy, mimics the action of GLP-1, a hormone produced in the intestine that regulates appetite and feelings of fullness, amycretin ups the ante. Besides mimicking GLP-1, it also activates receptors for amylin, a hormone that is produced in the pancreas and is involved in suppressing appetite and reducing food intake. In a preliminary trial, patients on amycretin lost 13% of their body weight after twelve weeks, double what has been seen with Wegovy. What makes this drug even more appealing is that unlike Ozempic, Wegovy and Mounjaro, is that instead of being injected, it can be administered as a pill taken once a day. Another potential benefit is a reduced risk of gastrointestinal symptoms such as nausea, vomiting and abdominal pain usually seen with GLP-1 agonists. The Eli Lilly Company believes it may have a winner in its experimental drug, retatrutide that in addition to being a GLP-1 agonist, mimics the action of two other hormones that control appetite. Retatrutide has to be injected, but Lilly is also experimenting with “orforglipron,” yet another GLP-1 agonist. The advantage with this drug is that not only can it be taken orally, it is also much easier to produce. Unlike the other drugs in this class that are peptides, that is chains of amino acids, orforglipron is a small molecule amenable to easier synthesis. Monlunabant is yet another drug ready to fight the battle of the bulge. Anyone who has ever tried cannabis will agree that it boosts the appetite. This is because it activates “cannabinoid receptors” located throughout the body. Novo Nordisk’s monlunabant is an oral “cannabinoid receptor inverse agonist” which means that it binds to a receptor and produces an effect opposite to an agonist. Since cannabidiol in cannabis increases appetite by fitting into a cannabinoid receptor, monlunabant has the opposite effect. It remains to be seen if these new drugs pan out, but the potential is there to have an impact on the obesity crisis.
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