Fractyl is developing treatments to regulate the body’s metabolic controller, the duodenum

Controlling the Metabolic Controller


Metabolic disease is a multi-organ pathology caused by insulin resistance which affects an estimated 1 billion people worldwide. Despite this high prevalence, the disease remains inadequately treated, with polypharmacy approaches managing the symptoms of the disease — such as hypertension, atherosclerosis, and high blood sugar — rather than addressing its underlying cause.

Recently, a new scientific understanding of metabolic disease has emerged that points to the central role of the small intestine. Fractyl’s pioneering research has revealed a mechanism by which to control this metabolic controller. Our therapeutic focus is on developing treatments that act on the duodenum to control metabolism broadly.

What’s the Duodenum?


The duodenum is the first section of the small intestine. It’s the first point in the intestine where nutrient absorption and hormonal signaling begins, immediately after food passes through the stomach. The lining of the intestine is the body’s largest endocrine organ, continuously sensing for the presence and type of ingested food in the gut and sending neurohormonal signals to the brain and the rest of the body.

In healthy diets, nutrients are absorbed throughout the length of the intestine. Unhealthy diets, such as those high in fats and sugars, are more easily digested, frontloading more of the nutrient absorption to the duodenum.

Duodenum

Role of the Duodenum in Type 2 Diabetes

The duodenum serves as a key regulator of metabolism by sending neurohormonal signals to the organs that regulate blood sugar and body weight.

Fractyl’s research has uncovered an important mechanism linking unhealthy diets to pathological changes in the duodenum and the development of metabolic diseases, including type 2 diabetes. When diets high in fats and sugars cause excessive nutrient absorption in the duodenum, the duodenum adapts by thickening its lining. A thickened lining causes the duodenum to absorb even more nutrients and inappropriately produce more signaling hormones, creating a cascade of events that lead to insulin resistance and weight gain.

DuodenumDiets high in fat and sugar result in thickened lining

Conversely, interventions on the duodenum may be able to reverse type 2 diabetes — an outcome which has already been clearly established thanks to research into the effects of bariatric surgeries. Certain bariatric surgeries that bypass the duodenum lead to immediate improvements in insulin resistance and blood sugar levels even before patients lose any weight. However, if nutrition is delivered to the duodenum again, the insulin resistance and high blood sugar return.

Treating Type 2 Diabetes via the Duodenum

Fractyl has developed an approach called duodenal mucosal resurfacing (DMR) to reverse the abnormal thickening of the duodenal lining and control the duodenum’s impact on metabolism. Revita® DMR is the only therapeutic option designed to address the root cause of type 2 diabetes.

Learn more about our therapies

Publications

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.

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.

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