Hot topics ADA 2024  

Biotech takes on chronic weight management

As Novo Nordisk and Lilly generate massive profits with weight-loss blockbusters Wegovy and Zepbound, several smaller players are looking to develop novel solutions that address some of the challenges with currently marketed products, including lean muscle mass loss and rebound weight gain.

Altimmune presented data from the Ph2 MOMENTUM trial evaluating GLP-1/glucagon dual receptor agonist pemvidutide in obesity. The company particularly highlighted preservation of muscle, with only 21.9% of weight loss attributed to lean mass loss. The company also shared positive data in dyslipidemia, showing reductions in total cholesterol, LDL-C and triglycerides.

Tern Pharmaceuticals shared preclinical data from the formerly shelved MASH drug TERN-501. In mouse model studies, TERN-501, in combination with semaglutide, showed 33% body weight loss over six weeks (comparable to the 35% weight loss seen with tirzepatide and superior to the 26% weight loss seen with semaglutide alone). Most interestingly, mice given the TERN-501 combination ate just as much as obese controls, suggesting the drug may cause metabolic adaption beyond just suppressing appetite. The TERN-501-treated mice also showed greater retention of lean muscle mass.

Fractyl Health also presented preclinical data on a novel weight loss agent, emphasizing durability of response. Their agent – a single-dose, GLP-1-based pancreatic gene therapy – showed positive results in a mouse model following post-semaglutide weight-gain rebound.

 

Diabetes technology improves outcomes

The role of technology in the management of diabetes was a major topic at ADA 2024, with data on AI-empowered apps, CGMs and smart insulin pumps.

Teladoc showed that predictive AI-modeling can increase patient engagement on their diabetes virtual care platform, ultimately driving greater A1C reductions. The studies presented at ADA demonstrated that “personalized health nudges” for patients with T2D increased engagement threefold, while yielding an additional 0.4 reduction in A1C. Data also showed that platform members who received personalized emails crafted with predictive modeling were 50% more likely to engage with coaching services compared to those who received a “standard” newsletter. Many studies show that use of 1:1 dedicated coaches can help improve overall diabetes control.

Multiple diabetes tech players also presented at ADA 2024. Dexcom showed the benefit of utilizing Dexcom CGMs in T2D, particularly alongside use of incretin therapies (e.g. GLP-1s). Meanwhile, on the automated insulin delivery front, Insulet’s SECURE-T2D pivotal trial showed that use of the Omipod 5 (a tubeless insulin pump) reduced A1C, time spent in hyperglycemia, and total daily insulin. At the same time, use of the pump improved overall time-in-range (TIR). The Omnipod 5 is available for integration with Dexcom and Abbot CGMs.

 

Diabetes-related comorbidities at the forefront

Along with data on weight loss and T2D improvements, major players Novo Nordisk and Eli Lilly presented data for their blockbuster molecules across a number of T2D comorbidities, including obstructive sleep apnea (OSA), chronic kidney disease (CKD) and heart failure (HF).

Novo presented data from the FLOW kidney outcomes trial, showing a 24% RRR in the composite primary outcome measure (time to occurrence of EGFR decline >50%, ESRD, death from kidney disease, or death from cardiovascular disease) for patients on semaglutide, with or without a background of an SGLT2i. Further, data from the SELECT and STEPF HFpEF trials showed semaglutide improved glucose control and provided a cardiovascular benefit (which was not dependent on degree of weight loss).

Lilly presented data from the SURMOUNT-OSA trial, which showed that tirzepatide reduced moderate-to-severe OSA severity by 62.8% (about 30 fewer events per hour), with up to 51.5% of participants on the highest dose of tirzepatide met the criteria for disease resolution.