But what if those figures are too low? While hurdles remain in terms of the drugs’ side effect profiles and payer backing, anti-obesity drugs could potentially find use for other conditions, concludes Truist director Dr. Joon Lee in a briefing note not specifically mentioning sales projections for the sector. In the long run, the drug class could find use not just for obesity but for conditions associated with elevated body weight. Examples run the gamut from neurodegenerative conditions such as Alzheimer’s to cancer to obstructive sleep apnea. A 2018 study proposed that obesity treatment may be a strategy to potentially prevent Alzheimer’s. Scientists have also tied obesity to fertility problems in both women and men owing to hormonal imbalances and other related health conditions.
One review proposed that GLP-1 drugs, despite their reputation of causing gastrointestinal side effects in some patients, could help obese patients with inflammatory bowel disease (IBD). The therapies’ “wealth of pleiotropic actions soon raised expectations that they might confer benefits on non-metabolic disorders,” the authors conclude.
GLP-1 receptors are present in several areas in the body, including in nerves, islets, heart, lung and the skin.
Near-term and long-term projections for obesity and beyond
While the potential of obesity drugs for such conditions could be considerable, it is unlikely to manifest in the near term. “We’re watching for osteoarthritis and NASH near term,” Lee noted, saying that the former conditions will be “interesting to watch.”
The current crop of GLP-1 drugs could fare well for the time being with semaglutide generics potentially arriving in 2032 or 2033 in the U.S.
Beyond GLP-1 drugs alone: RNAi and incretin combinations
Recent research on the genetic factors that contribute to obesity could point to further breakthroughs down the road. Genome-wide association studies (GWAS), for instance, have identified numerous genes tied to obesity, including the INHBE gene, which could be a promising therapeutic target. By modulating these genes, researchers could counteract the evolutionary adaptations that once served humans well in times of food scarcity but now contribute to the obesity epidemic. Alnylam plans to explore INHBE as a RNA interference (RNAi) therapeutic target for cardiometabolic disease.
By targeting genes linked to fat metabolism, appetite control, and insulin sensitivity, RNAi offers a selective approach to modulate biological pathways involved in obesity. Researchers are also testing its potential in associated metabolic disorders such as type 2 diabetes, hyperlipidemia, and NASH.
Truist posits that GLP1s and combinations with other incretins or nutrient-stimulated hormones such as amylin could dominate the obesity market in the coming years. In the longer term, the firm projects that strategies focusing on foundational biological processes associated with obesity could be more effective than more downstream approaches.
Filed Under: Cardiovascular, Gastroenterology, Metabolic disease/endicrinology, Neurological Disease