Translating Anti-Diabetic Effects of Bariatric Surgery into Therapeutics
The drug discovery efforts at Nivarta are focused on translating the mechanisms that drive diabetes remission and weight loss following metabolic surgery into therapeutics. Metabolic surgery that involves gut repositioning is currently the most effective treatment for severe obesity. The data shows that gastric bypass leads up to sixty percent EWL (Excessive Weight Loss) in obese individuals within months following the surgery. In addition, a complete remission of diabetes was observed in about seventy percent of these obese subjects within weeks. Similar results are also seen in rodent models after performing roux-en-y gastric bypass (RYGB) surgery in studies conducted by Dr. Nicholas Stylopoulos. A twenty five percent weight loss was observed within weeks and was found to be sustained all through the study (twenty four weeks). The glucose homeostasis was restored to pre-diabetic state in these rodents. While the surgery is yielding tremendous benefits, it is highly invasive and non-reversible procedure. Hence, there is a significant interest in the industry to develop alternative strategies based on protein therapeutics and small molecules that reproduce the anti-diabetic and anti-obesity effects of metabolic surgery.
- RESEARCH ARTICLE: Saeidi N, Meoli L, Nestoridi E, Gupta NK, Kvas S, Kucharczyk J, Bonab AA, Fischman AJ, Yarmush ML, Stylopoulos N. Reprogramming of intestinal glucose metabolism and glycemic control in rats after gastric bypass, Science. 2013 Jul 26;341(6144):406-10. [PMID: 23888041]
- COMMENTS: Koch L. Surgery: T2DM remission after RYGB-a ‘gutsy’ move., Nat Rev Endocrinol. 2013 Oct;9(10):564. [PMID: 23938283]
- COMMENTS: Berthoud HR. Medicine. Why does gastric bypass surgery work?. Science. 2013 Jul 26;341(6144):351-2 [PMID: 23888026]
- RESEARCH ARTICLE: Stylopoulos N, Hoppin AG, and Kaplan LM.. Roux-en-Y Gastric Bypass Enhances Energy Expenditure and Extends Lifespan in Diet-induced Obese Rats, Obesity (2009) 17, 1839–1847. [PMID: 19556976]
- RESEARCH ARTICLE: Padwal R, Klarenbach S, Wiebe N, Birch D, Karmali S, Manns B, Hazel M, Sharma AM, and Tonelli M. Bariatric surgery: a systematic review and network meta-analysis of randomized trials. Obesity Reviews (2011) 12, 602–621 [PMID: 21438991]