title: Niacin Alternatives for Dyslipidemia: Fool's Gold or Gold Mine? Part II: Novel Niacin Mimetics.
abstract: Two cardiovascular outcome trials established niacin 3 g daily prevents hard cardiac events. However, as detailed in part I of this series, an extended-release (ER) alternative at only 2 g nightly demonstrated no comparable benefits in two outcome trials, implying the alternative is not equivalent to the established cardioprotective regimen. Since statins leave a significant treatment gap, this presents a major opportunity for developers. Importantly, the established regimen is cardioprotective, so the pathway is likely beneficial. Moreover, though effective, the established cardioprotective regimen is cumbersome, limiting clinical use. At the same time, the ER alternative has been thoroughly discredited as a viable substitute for the established cardioprotective regimen. Therefore, by exploiting the pathway and skillfully avoiding the problems with the established cardioprotective regimen and the ER alternative, developers could validate cardioprotective variations facing little meaningful competition from their predecessors. Thus, shrewd developers could effectively tap into a gold mine at the grave of the ER alternative. The GPR109A receptor was discovered a decade ago, leading to a large body of evidence commending the niacin pathway to a lower cardiovascular risk beyond statins. While mediating niacin's most prominent adverse effects, GPR109A also seems to mediate anti-lipolytic, anti-inflammatory, and anti-atherogenic effects of niacin. Several developers are investing heavily in novel strategies to exploit niacin's therapeutic pathways. These include selective GPR109A receptor agonists, niacin prodrugs, and a niacin metabolite, with encouraging early phase human data. In part II of this review, we summarize the accumulated results of these early phase studies of emerging niacin mimetics.
authors.affiliation: Department of Medicine, York Hospital, 1001 S. George Street, York, PA, 17403, USA. harsh_goel@hotmail.com.
authors.forename: Harsh
authors.initials: H
authors.lastname: Goel
authors.affiliation: Department of Medicine, Division of Cardiovascular Medicine, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA. richard.dunbar@uphs.upenn.edu.|Division of Translational Medicine and Human Genetics, Perelman School of Medicine at the University of Pennsylvania, 3600 Spruce Street, 9-010 Maloney Building, Philadelphia, PA, 19104, USA. richard.dunbar@uphs.upenn.edu.|Institute for Translational Medicine and Therapeutics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA. richard.dunbar@uphs.upenn.edu.|The Cardiovascular Institute, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA. richard.dunbar@uphs.upenn.edu.|Institute for Diabetes, Obesity, and Metabolism, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA, USA. richard.dunbar@uphs.upenn.edu.
authors.forename: Richard L
authors.initials: RL
authors.lastname: Dunbar
mesh_terms: D000818:Animals; D040761:Biomimetic Materials / Q000627:therapeutic use*; D002318:Cardiovascular Diseases / Q000188:drug therapy; D002784:Cholesterol / Q000378:metabolism; D050171:Dyslipidemias / Q000188:drug therapy*; D006801:Humans; D000960:Hypolipidemic Agents / Q000627:therapeutic use*; D050356:Lipid Metabolism; D009525:Niacin / Q000627:therapeutic use*
chemical_list: D000960:Hypolipidemic Agents; D009525:Niacin; D002784:Cholesterol
keywords: GPR109A agonists; Hyperlipidemia; Lipids; Niacin; Niacin conjugates; Niacin prodrugs; Nicotinic acid