What is Type 2 Diabetes?
T2D is a progressive metabolic disorder of rising blood sugar.
Modern changes in diet and lifestyle have led to an increase in metabolic diseases around the world, as depicted by data from the International Diabetes Federation projecting rapid growth of diabetes from 2019 to 2045.
Learn more about the growing T2D epidemic: Saeedi et al. Diabetes Res Clin Pract. 2019
What causes T2D?
T2D is caused by two parallel, progressive disease processes within the body: insulin resistance and insulin insufficiency.
Insulin resistance is the inability of the body to respond to the hormone insulin and remove sugar from the bloodstream.
Insulin insufficiency in T2D is the gradual failure of the pancreas to produce enough insulin to meet the body’s needs.
Insulin resistance and insulin insufficiency are interrelated. Insulin resistance forces the pancreas to produce more insulin, which ultimately leads to the progressive loss of insulin production in the pancreas. This combination of insulin resistance and consequent insulin insufficiency results in high blood sugar levels.
High blood sugar levels drive the development of diseases in small blood vessels (e.g., microvascular diseases in the eye, kidney, and nerves) and large blood vessels (e.g., macrovascular diseases in the heart and brain). The resulting damage can potentially lead to life-threatening complications, including the risk of early death.
Learn more about the development of T2D:
Masato Kasuga. J Clin Invest. 2006
Galicia-Garcia et al. Int J Mol Sci. 2020
Marlon E. Cerf. Front Endocrinol. 2013
Dal Canto et al. Eur J Prev Cardiol. 2019
What is the unmet need in T2D?
Despite the availability of more than 60 approved medicines, nearly 50% of patients with T2D are still not achieving adequate glucose control in the U.S. today. This is because current therapies focus on managing blood sugar symptoms rather than attempting to correct the underlying disease processes in the body causing insulin resistance and insulin insufficiency.
There are no approved therapies in T2D today that offer durable disease modification. As a result, there are no therapies that can halt the progressive worsening of the disease.
Our potentially disease-modifying therapies are designed to target and improve the function of the diseased organs responsible for these two root causes of T2D— insulin resistance arising from the duodenum (the proximal intestine) and insulin insufficiency arising from the pancreas.
Revita® targets insulin resistance
Rejuva® targets insulin insufficiency
What is the role of the Duodenal Dysfunction in T2D?
The duodenum serves as a key regulator of metabolism by sending neurohormonal signals to the organs that regulate blood sugar and body weight. Research conducted both by Fractyl Health and multiple independent scientific groups around the world has uncovered an important mechanism linking unhealthy diets to pathological changes in the duodenum and the development of metabolic diseases, including T2D. These changes are called duodenal dysfunction.
- Long-term exposure to high-fat and high-sugar diets has been proposed to cause changes to the structure and function of the duodenal lining (the duodenal mucosa).
- This duodenal mucosal dysfunction may disrupt neural and hormonal signals from the duodenum to the brain and the rest of the body.
- These altered signals are thought to lead to metabolic disease.
The Revita Duodenal Mucosal Resurfacing (DMR)® system, or Revita®, our lead product candidate, is designed to remodel the duodenal lining via hydrothermal ablation in order to edit these abnormal intestinal signals. By addressing duodenal dysfunction, Revita® potentially enables protection from the underlying causes of disease progression which drives T2D.
Learn more about Revita®What is the role of the Pancreas in T2D?
The pancreas is an organ that produces hormones (including insulin, which is produced by beta cells in the pancreas) to help manage blood sugar levels. In people with T2D, the pancreas’ ability to produce insulin begins to fail over the course of many years due to exhaustion of the beta cells from overwork and damage to the beta cells from circulating toxins tied to insulin resistance.
Rejuva®, our novel gene therapy platform, consists of gene therapy candidates that are being developed to target the dysfunctional pancreatic beta cells that are a root cause of insulin insufficiency in T2D.
Learn more about Rejuva®Publications and Footnotes
2022
Meiring, et al. Eliminating exogenous insulin therapy in patients with type 2 diabetes by duodenal ablation and GLP-1 RA decreases risk scores for cardiovascular events. Cardiovascular Diabetology, 21:191, 2022.
van Baar, et al. Durable metabolic improvements 2 years after duodenal mucosal resurfacing (DMR) in patients with type 2 diabetes (REVITA-1 Study) Diabetes Research and Clinical Practice, 13 January 2022.
Meiring, et al. DMR with a GLP-1 receptor agonist increases postprandial unconjugated bile acids in patients with insulin-dependent T2D. American Journal of Physiology, Endocrinology and Metabolism, E132–E140, 31 January 2022.
Meiring, et al. A Changed Gut Microbiota Diversity Is Associated With Metabolic Improvements After Duodenal Mucosal Resurfacing With Glucagon-Like-Peptide-1 Receptor Agonist in Type 2 Diabetes in a Pilot Study, Frontiers in Clinical Diabetes and Healthcare, 05 July 2022.
2021
Rajagopalan, et al. “A Gut-Centric Model of Metabolic Homeostasis.” Journal of Diabetes Science and Technology, 0:1-08, October 2021.
Mingrone, et al. “Safety and efficacy of hydrothermal duodenal mucosal resurfacing in patients with type 2 diabetes: the randomised, double-blind, sham-controlled, multicentre REVITA-2 feasibility trial.” Gut, 0:1-11, January 2021.
2020
van Baar, et al. “Duodenal mucosal resurfacing combined with GLP-1RA to discontinue insulin in type 2 diabetes: a feasibility study.” Gastrointestinal Endoscopy, 0:1-10, December 2020.
van Baar, et al. “Duodenal mucosal resurfacing: Multicenter experience implementing a minimally invasive endoscopic procedure for treatment of type 2 diabetes mellitus.” Endoscopy International Open; 08: E1683–E1689, October 2020.
van Baar, et al. “Endoscopic duodenal mucosal resurfacing for the treatment of type 2 diabetes mellitus: one year results from the first international, open-label, prospective, multicentre study.” Gut, 69:295-303, January 2020.
2019
van Baar, et al. “Endoscopic duodenal mucosal resurfacing improves glycaemic and hepatic indices in type 2 diabetes: 6-month multicentre results.” JHEP Reports, Volume 1, Issue 6, 429-437, November 2019.
Haidry, et al. “Duodenal mucosal resurfacing: proof-of-concept, procedural development, and initial implementation in the clinical setting.” Gastrointestinal Endoscopy, Volume 90, Issue 4, 673-681.e2, October 2019.
2017
Cherrington, et al. “Hydrothermal Duodenal Mucosal Resurfacing Role in the Treatment of Metabolic Disease.” Gastrointestinal Endoscopy Clinics of North America, 27(2): 299-311, April 2017.
2016
Rajagopalan, et al. “Endoscopic Duodenal Mucosal Resurfacing for the Treatment of Type 2 Diabetes: 6-Month Interim Analysis From the First-in-Human Proof-of-Concept Study.” Diabetes Care, 39, 1-8, August 2016.
Galvao, et al. “Hydrothermal duodenal mucosal resurfacing: a novel procedural therapy for metabolic disease.” VideoGIE, 1(1), 10-11, September 2016.
2023
Rajagopalan, et al. American Diabetes Association 2023, San Diego, CA, June 2023
Fonseca, et al. American Diabetes Association 2023, San Diego, CA, June 2023
Galvani, et al. Digestive Disease Week (DDW) 2023, Chicago, IL USA, May 2023
Rajagopalan, et al. American Society of Gene and Cell Therapy, Los Angels, CA, May 2023
Rajagopalan, et al. American Society of Gene and Cell Therapy, Los Angels, CA, May 2023
2022
Liou, et al. World Congress on Insulin Resistance, Diabetes and Cardiovascular Disease (WCIRDC), Universal City, CA, Dec 2022
Busch, et al. United European Gastroenterology Week (UEGW), Vienna, Austria, Oct 2022
Meiring, et al. Digestive Disease Week (DDW) 2022, San Diego, CA, USA, May 2022
2021
Meiring, et al. Digestive Disease Week (DDW) 2021, Virtual, May 2021
2020
Meirling, et al. United European Gastroenterology Week 2020. Virtual, October 2020.
Chouhan, et al. ISMRM & SMRT Virtual Conference & Exhibition. Virtual, August 2020.
Hopkins, et al. Endocrine Online 2020 (ENDO). Virtual, June 2020.
Mingrone, et al. 80th American Diabetes Association Scientific Sessions (ADA). Virtual, June 2020.
Chouhan, et al. European Society of Gastrointestinal and Abdominal Radiology 2020 Virtual Congress (ESGAR). Amsterdam, The Netherlands, May 2020.
Chouhan, et al. European Society of Gastrointestinal and Abdominal Radiology 2020 Virtual Congress (ESGAR). Amsterdam, The Netherlands, May 2020.
2019
Lopez-Talavera, et al. Diabetes Technology Meeting (DTM). North Bethesda, MD, November 2019.
van Baar, et al. Diabetes Technology Meeting (DTM). North Bethesda, MD, November 2019.
West, et al. ObesityWeek 2019. Las Vegas, NV, November 2019.
Bergman, et al. American Association for the Study of Liver Diseases (AASLD). Boston, MA, November 2019.
van Baar, et al. United European Gastroenterology Week 2019 (UEGW). Barcelona, Spain, October 2019.
Meiring, et al. 79th American Diabetes Association Scientific Sessions (ADA). San Francisco, California, USA, June 2019.
Hopkins. 4th World Congress on Interventional Therapies for Type 2 Diabetes (WCITD). New York City, NY, USA, April 2019.
Hopkins, et al. 4th World Congress on Interventional Therapies for Type 2 Diabetes (WCITD). New York City, NY, USA, April 2019.
2018
Haidry, et al. Digestive Disease Week – Monumental Developments in Science & Medicine (DDW). Washington, DC, USA, June 2018.
Ghosh, et al. 78th American Diabetes Association Scientific Sessions (ADA). Orlando, Florida, USA, June 2018.
van Baar, et al. 78th American Diabetes Association Scientific Sessions (ADA). Orlando, Florida, USA, June 2018.
deGravelle, et al. 4th Paris Nash Meeting. Paris, France, July 2018.
Maggs, et al. 4th Paris Nash Meeting. Paris, France, July 2018.
van Baar, et al. United European Gastroenterology Week (UEGW). Vienna, Austria, October 2018.
Maggs, et al. American Association for the Study of Liver Diseases (AASLD). San Francisco, Calif., USA, November 2018.
2017
van Baar, et al. Digestive Disease Week (DDW). Chicago, Illinois, USA, May 2017.
Rajagopalan. 3rd Paris Nash Meeting. Paris, France, July 2017.
van Baar, et al. 53rd Annual Meeting of the European Association for the Study of Diabetes (EASD). Lisbon, Portugal, September 2017.
van Baar, et al. American Association for the Study of Liver Diseases (AASLD). Washington, DC, USA, October 2017.
Sacks, et al. American Heart Association Meeting (AHA). Anaheim, Calif., USA, November 2017.
2016
Rajagopalan, et al. 9th Diabetes Drug Discovery & Development Conference-GTC Diabetes Summit. Boston, Massachusetts, USA, April 2016.
Rajagopalan, et al. The International Liver Congress-European Association for the Study of the Liver (EASL). Barcelona, Spain, April 2016.
Rajagopalan, et al. The International Liver Congress-European Association for the Study of the Liver (EASL). Barcelona, Spain, April 2016.
Galvao Neto, et al. Digestive Disease Week (DDW). San Diego, Calif, USA, May 2016.
Rajagopalan, et al. Digestive Disease Week (DDW). San Diego, Calif, USA, May 2016.
van Baar, et al. Digestive Disease Week (DDW). San Diego, Calif, USA, May 2016
Cherrington, et al. 76th American Diabetes Association (ADA). New Orleans, Louisiana, USA, June 2016. [Oral]
Maggs. The Obesity Society (TOS). New Orleans, LA, USA, October 2016
van Baar, et al. United European Gastroenterology Week (UEGW). Vienna, Austria, October 2016
Rajagopalan, et al. American Association for the Study of Liver Diseases (AASLD). Boston, Massachusetts, USA, November 2016.
van Baar, et al. American Association for the Study of Liver Diseases (AASLD). Boston, Massachusetts, USA, November 2016.
2015
Cherrington, et al. Third World Congress on Interventional Therapies for Type 2 Diabetes (WCITT2D). London, UK, September 2015.
Cherrington, et al. United European Gastroenterology Week (UEGW). Barcelona, Spain, October 2015.
Cherrington, et al. 13th World Congress on Insulin Resistance, Diabetes & Cardiovascular Disease (WCIRS). Los Angeles, Calif., USA, December 2015.
2014
Rajagopalan. 50th Annual Meeting of the European Association for the Study of Diabetes (EASD). Vienna, Austria, September 2014.
Holleman. 50th Annual Meeting of the European Association for the Study of Diabetes (EASD). Vienna, Austria, September 2014.
Rubino. 50th Annual Meeting of the European Association for the Study of Diabetes (EASD). Vienna, Austria, September 2014.
Galvao, et al. World Congress of the International Federation for the Surgery of Obesity and Metabolic Disorders (IFSO). Montreal, Canada, August 2014.
Saeedi et al. Diabetes Res Clin Pract. 2019
Masato Kasuga. J Clin Invest. 2006
Galicia-Garcia et al. Int J Mol Sci. 2020
Fang et al. N Engl J Med. 2021
Dal Canto et al. Eur J Prev Cardiol. 2019
Duca et al. Cell Met. 2015
West et al. Obesity Week. 2019
Aliluev et al. Nat Metab. 2021
Taylor et al. Nat. 2021
Mah et al. Endocrinol. 2014
Baldassano et al. J Endocrinol. 2013
Mao et al. Diab. 2013
Dailey et al. Physiol Behav. 2014
Marlon E. Cerf. Front Endocrinol. 2013
Vivian A. Fonseca. Diabetes Care. 2009
Kevin Cowart. Clin Diabetes. 2020
Umpierrez et al. Diabetes Obes Metab. 2019
Vijan et al. J Gen Intern Med. 2005
Swinnen et al. Diabetes Care. 2009
Jing Luo and Walid F Gellad. Curr Diab Rep. 2020