Novel triglyceride-lowering therapies, including apolipoprotein C-III inhibitors and FGF-21 analogues, have pronounced triglyceride-lowering effects and clinical benefits for specific indications.
What are the target populations and current evidence for novel triglyceride-lowering therapies?
Novel triglyceride-lowering therapies show promise in reducing acute pancreatitis and MASH, but their impact on atherosclerotic cardiovascular disease risk remains to be established.
Lipoprotein lipase regulates triglyceride hydrolysis and contributes to cellular uptake of triglyceride-rich lipoprotein remnants. Multiple pathways modulate lipoprotein lipase activity, which has prompted interest in the development of drugs that increase lipoprotein lipase activity as means to reduce risk for acute pancreatitis, atherosclerotic cardiovascular disease, and metabolic dysfunction-associated steatohepatitis through reduction of circulating triglycerides and remnant cholesterol. The authors provide an overview of the target populations for agents that lower triglycerides and remnant cholesterol through increased lipoprotein lipase activity, the drugs being developed for these indications, including apolipoprotein C-III and angiopoietin-like protein 3, 3/8, and 4 inhibitors, and the epidemiologic and genetic evidence supporting the use of these drugs for the prevention of atherosclerotic cardiovascular disease and acute pancreatitis. In addition, the authors provide a corresponding overview of fibroblast growth factor-21 analogues that share many characteristics with these novel triglyceride-lowering drugs. Apolipoprotein C-III inhibitors, angiopoietin-like protein 3, 3/8, and 4 inhibitors, and fibroblast growth factor-21 analogues have pronounced triglyceride-lowering and remnant cholesterol-lowering effects. In clinical trials, apolipoprotein C-III inhibitors have been shown to lower risk for acute pancreatitis in patients with severe hypertriglyceridemia and are approved for this indication, while fibroblast growth factor-21 analogues reduce hepatic steatosis and fibrosis in patients with metabolic dysfunction-associated steatohepatitis. It remains to be seen whether these novel drugs may lower risk for atherosclerotic cardiovascular disease as well.
Nordestgaard et al. (Thu,) conducted a review in Hypertriglyceridemia, acute pancreatitis, atherosclerotic cardiovascular disease, metabolic dysfunction-associated steatohepatitis. Novel triglyceride-lowering therapies (apolipoprotein C-III inhibitors, angiopoietin-like protein inhibitors, fibroblast growth factor-21 analogues) was evaluated. Novel triglyceride-lowering therapies, including apolipoprotein C-III inhibitors and FGF-21 analogues, have pronounced triglyceride-lowering effects and clinical benefits for specific indications.
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