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The discussion shifts to the challenges behind collaborating in a field that, as Naim puts it, “no one has figured out what to do with.” Mazen calls on the “larger companies” to work with the smaller ones to make these studies more common, noting that the economics and risk profiles of smaller companies require them to focus on getting a single drug to market as quickly as possible. Naim notes that precedent has taken form in Hepatitis C. It was very difficult to treat and different companies’ drugs were combined for a while until each company figured out their own combination and that collaboration stopped.

A debate next emerges when Naim describes LEGEND, a trial combining the promising PPAR agonist with the SGLT-2 agent, empagliflozin. Naim describes empa as an excellent agent to counteract potential weight gain with lani. Mazen shares his belief that the trial should have combined lani with a drug that provides greater weight loss, possibly a GLP-1 agonist or dual agonist. Roger suggests it depends on the target: liver and metabolic disease targeting might lead to a PPAR/GLP-1 combination, while a more holistic look at metabolic outcomes might prefer SGLT-2s for their proven beneficial effects on kidney and cardiovascular diseases.