Objective: To review the pathophysiology, pharmacology, and current or future therapies under study for use in treating diabetes mellitus, inflammation associated with diabetes mellitus, and/or obesity related to diabetes mellitus, through 1 of 4 investigational pathways: adiponectin, ghrelin, resveratrol, or leptin.
Data sources: A literature search using MEDLINE (1966-December 12, 2009), PubMed (1950-December 12, 2009), Science Direct (1994-December 12, 2009), and International Pharmaceutical Abstracts (1970-December 12, 2009) was performed using the terms adiponectin, ghrelin, resveratrol, leptin, inflammation, obesity, and diabetes mellitus. English-language, original research, and review articles were examined, and citations from these articles were assessed as well.
Study selection and data extraction: Clinical studies and in vitro studies were included in addition to any Phase 1, 2, or 3 clinical trials.
Data synthesis: Mechanistic pathways regarding adiponectin, ghrelin, resveratrol, and leptin are of interest as future treatment options for diabetes mellitus. Each of these pathways has produced significant in vitro and in vivo clinical data warranting further research as a possible treatment pathway for diabetes-related inflammation and/or obesity reduction. While research is still underway to determine the exact effects these pathways have on metabolic function, current data suggest that each of these compounds may be of interest for future therapies.
Conclusions: While several pathways under investigation may offer additional benefits in the treatment of diabetes mellitus and associated impairments, further investigation is necessary for both investigational and approved therapies to ensure that the impact in new pathways does not increase risks to patient safety and outcomes.