Therapeutics
obese diabetic and non-diabetic patients undergo- ing gastric banding or bypass surgery. Blood and tissue samples will be harvested from these patients at the time of surgery and during longitudinal fol- low-up over a period of up to five years. The pro- filing of gene and protein expression in these sam- ples will provide valuable insight into novel thera- peutic targets for T2DM. Taken together, these two cohorts recruited by
the IT-Diab consortium provide innovative and complementary clinical tools for the cross-valida- tion of newly identified therapeutic targets in T2DM. In conjunction with cutting-edge transla- tional technology, these approaches may thus pro- vide new areas of research for the discovery and development of novel T2DM therapies.
Summary
The past 30 years have witnessed a revolution in diabetes management, with a move away from simple insulin treatment for glycemic control to improved understanding of the underlying mecha- nisms of the pathology, and the development of an impressive number of potential therapeutic approaches. Unfortunately, at the same time, sedentary lifestyles and the explosion of unbal- anced dietary habits have led to the current obesi- ty pandemic, with the worldwide obese population now estimated at 300 million. Due to the high association between obesity and T2DM, there is thus an ever-growing need to improve prediabetes and diabetes diagnosis and management. While treatment strategies have undeniably progressed, the International Diabetes Federation considers that many, if not the majority, of diabetic patients still have unmet medical needs.
Indeed, the benefit of aggressive HbA1c-lower- ing therapy has been questioned by major clinical trials such as ACCORD, ADVANCE and VADT, in which the intensive control of HbA1c levels had beneficial effects on microvascular diabetic compli- cations, but did not reduce macrovascular disease or overall mortality3. It is thus now recognised that future anti-diabetic strategies should be designed to address multiple clinical endpoints related to the multifactorial nature of T2DM.
A wide range of different therapeutic approach- es are being applied to tackle the multifactorial nature of T2DM, as discussed here, and the
ClinicalTrials.gov website currently lists almost 1,000 active Type 2 diabetes trials worldwide. The inclusion of cardiovascular parameters in the study endpoints of these trials, together with the growing awareness of the importance of tackling cardiometabolic disease, including associated
Drug Discovery World Summer 2011
Dr Lesley Millatt completed post-doctoral training at the University of Virginia, and in 2000 joined Genfit, a biopharmaceutical company focused on the early diagnosis and treatment of diabetes and related disorders (from risk factors to complica- tions).
Dr Rémy Hanf is in charge of Drug Development & Translational Research at Genfit. Before joining Genfit in 2003, he held various R&D management positions in pharmaceutical companies involved in cardiovascular and metabolic disorders.
Dr Dean W Hum joined Genfit in 2000 and is presently responsible for Scientific Affairs. Before joining Genfit he was Associate Professor at Laval University, where he worked on functional genomics and the regulation of gene transcription in Endocrinology.
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liver diseases, as a whole, means that the coming years hold great promise for the identification of novel therapeutic strategies for T2DM and its associated diseases.
DDW
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35 Hanf, R, Hum, DW, Staels, B. GFT505 Efficacy and Safety in Healthy Volunteers and Patients Suffering from Atherogenic Dyslipidemia. American Diabetes Association, 70th Scientific Session, 2010. 36 Buchwald, H et al. Bariatric surgery: a systematic review and meta-analysis. JAMA, 2004. 292(14): p. 1724-37. 37 Cummings, DE et al. Role of the bypassed proximal intestine in the anti-diabetic effects of bariatric surgery. Surg Obes Relat Dis, 2007. 3(2): p. 109-15. 38 Rubino, F et al. The mechanism of diabetes control after gastrointestinal bypass surgery reveals a role of the proximal small intestine in the pathophysiology of type 2 diabetes. Ann Surg, 2006. 244(5): p. 741-9. 39 Caiazzo, R et al. Gastric bypass and glucose metabolism. Diabetes Metab, 2009. 35(6 Pt 2): p. 528-31.
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