Metabolic disease drug discovery- "hitting the target" is easier said than done.

Despite the advent of new drug classes, the global epidemic of cardiometabolic disease has not abated. Continuing unmet medical needs remain a major driver for new research. Drug discovery approaches in this field have mirrored industry trends, leading to a recent increase in the number of molecules entering development. However, worrisome trends and newer hurdles are also apparent. The history of two newer drug classes-glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors-illustrates both progress and challenges. Future success requires that researchers learn from these experiences and continue to explore and apply new technology platforms and research paradigms.