2024 was another banner year for GLP-1 receptor agonists (GLP-1RAs) on multiple fronts. They continued to expand into new indications, and provide their developers with both rich remuneration and scientific acclamation. There are now seven approved GLP-1RAs. Commercially, the most successful one so far is semaglutide, sold under the brand name Wegovy or Ozempic depending on the indication.

First, the good news about pandemics – and in 2024, there was big “good news.” Science Magazine named lenacapavir (Gilead Sciences Inc.) as the Breakthrough of the Year. In two separate trials, lenacapavir prevented HIV transmission with 100% efficacy in cisgender African women and 99.9% efficacy in men and gender-diverse persons when administered twice a year.

The acquisition of Karuna Therapeutics Inc. by Bristol Myers Squibb Co. (BMS) was announced in December 2023, and closed as the BioEurope Spring meeting was convening in March. Along with the acquisition of Cerevel Therapeutics Inc. by Abbvie Inc., the deal signaled that big pharma companies were ready to get back into the brain diseases space.

Researchers at the University of Leipzig and ETH Zurich have used single-cell sequencing to identify differences between fat tissue of obese individuals who are metabolically unhealthy, and those who were in good metabolic health. The findings, which were published online Dec. 17, 2024, in Cell Metabolism, identify measurements that can be used to decouple obesity from metabolic disease.

Cancer and autoimmunity are “often thought of as being at opposite ends of the immune response,” Ana Anderson told her audience at a joint meeting of the NIH’s Office of Autoimmune Disease Research and Office of Research in Women’s Health earlier this month. Cancer, that line of reasoning goes, arises when the immune system is not good enough at recognizing harmful autoantigens. Autoimmunity arises when it is hypervigilant, mistaking harmless autoantigens for problematic ones and going on the attack.

Investigators at the Helmholtz Institute have shown that inceptor, an inhibitor of the insulin signaling pathway, acted by binding insulin and targeting it for degradation. “Insulin was discovered 100 years ago, and the insulin receptor was discovered 50 years ago,” Heiko Lickert told BioWorld. “Now we have a new insulin receptor, which degrades insulin.” Lickert is the senior author of the paper reporting the new insights into how inceptor works, which were published online in Nature Metabolism.

Investigators at the Helmholtz Institute have shown that inceptor, an inhibitor of the insulin signaling pathway, acted by binding insulin and targeting it for degradation. “Insulin was discovered 100 years ago, and the insulin receptor was discovered 50 years ago,” Heiko Lickert told BioWorld. “Now we have a new insulin receptor, which degrades insulin.” Lickert is the senior author of the paper reporting the new insights into how inceptor works, which were published online in Nature Metabolism.

Researchers at the University of Rochester have described a neuroimaging-based biomarker that could identify individuals with early psychosis, and improved their identification when it was added to a standard neurocognitive diagnostic test. In a group of roughly 160 participants in the Human Connectome Early Psychosis Project, individuals who were in the early stages of psychosis had stronger connections from the thalamus (a midbrain sensory processing area) to the cortex, but weaker connections between different cortical areas, than controls.

Researchers at the University of Copenhagen have identified a signaling pathway that simultaneously increased energy expenditure and decreased food intake. In both human and primate studies, agonists of the tachykinin NK2 receptor (NK2R) led to both decreased food intake and increased energy expenditure. And in behavioral tests, they were not aversive, suggesting they do not cause the nausea that is a major side effect of GLP-1 agonists.

Fat cells from patients who had lost weight after bariatric surgery, as well as from animals who had gained and then lost weight, were transcriptionally distinct from cells that had not experienced such weight changes at the organism level. In the animal studies, those transcriptional changes were due to epigenetic changes. The findings, which were published online in Nature on Nov. 18, 2024, are a possible molecular-level explanation for the short-term nature of most weight loss.