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Sotagliflozin: First Global Approval

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Abstract

Sotagliflozin (Zynquista™) is a dual inhibitor of sodium-glucose co-transporters (SGLT) 1 and 2 being developed by Lexicon Pharmaceuticals and Sanofi as a treatment for type 1 (T1DM) and type 2 diabetes mellitus (T2DM). The drug has a dual action, blunting and delaying absorption of glucose from the gastrointestinal tract and the reabsorption of glucose in the proximal tubule of the kidney, respectively. In the phase III inTandem clinical trial program in patients with T1DM, sotagliflozin as an adjunct to optimised insulin therapy produced a clinically meaningful reduction in HbA1c levels, but was associated with a higher incidence of diabetic ketoacidosis than placebo. Sotagliflozin was recently approved for use as an adjunct to insulin in T1DM in the EU. However, the FDA Endocrinologic and Metabolic Drugs Advisory Committee was divided, citing concerns regarding diabetic ketoacidosis, leading the FDA to issue an Complete Response Letter for this indication in the USA. This article summarizes the milestones in the development of sotagliflozin leading to this first approval in the EU as an adjunct to insulin in patients with T1DM with a body mass index ≥ 27 kg/m2 who have failed to achieve adequate glycaemic control despite optimal insulin therapy.

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References

  1. Sanofi. Zynquista™ now approved in the European Union for treatment of adults with type 1 diabetes [media release]. 26 April 2019. http://www.sanofi.com.

  2. Mudaliar S, Polidori D, Zambrowicz B, et al. Sodium-glucose cotransporter inhibitors: effects on renal and intestinal glucose transport. From bench to bedside. Diabetes Care. 2015;38(12):2344–53.

    Article  CAS  PubMed  Google Scholar 

  3. European Medicines Agency. Zynquista (sotagliflozin): EU prescribing information. 2019. http://ec.europa.eu/health/documents/community-register/2019/20190426144497/anx_144497_en.pdf. Accessed 7 May 2019.

  4. Sanofi. FDA to review Zynquista™ (sotagliflozin) as potential treatment for type 1 diabetes [media release]. 22 May 2018. http://www.sanofi.com.

  5. Sanofi. FDA issues Complete Response Letter for Zynquista™ (sotagliflozin) [media release]. 22 Mar 2019. http://www.sanofi.com.

  6. Sanofi. Sanofi and Lexicon Pharmaceuticals to collaborate on sotagliflozin, an investigational new oral medicine for people with diabetes [media release]. 6 Nov 2015. http://www.sanofi.com.

  7. Lexicon Pharmaceuticals. Lexicon Pharmaceuticals announces opt-in decision for U.S. co-promotion of sotagliflozin with Sanofi in type 1 diabetes [media release]. 31 July 2017. http://www.lexpharma.com.

  8. Lapuerta P, Zambrowicz B, Strumph P, et al. Development of sotagliflozin, a dual sodium-dependent glucose transporter 1/2 inhibitor. Diabetes Vasc Dis Res. 2015;12(2):101–10.

    Article  CAS  Google Scholar 

  9. Powell DR, DaCosta CM, Smith M, et al. Effect of LX4211 on glucose homeostasis and body composition in preclinical models. J Pharmacol Exp Ther. 2014;350(2):232–42.

    Article  CAS  PubMed  Google Scholar 

  10. Powell DR, Smith M, Greer J, et al. LX4211 increases serum glucagon-like peptide 1 and peptide YY levels by reducing sodium/glucose cotransporter 1 (SGLT1)-mediated absorption of intestinal glucose. J Pharmacol Exp Ther. 2013;345(2):250–9.

    Article  CAS  PubMed  Google Scholar 

  11. Zambrowicz B, Freiman J, Brown PM, et al. LX4211, a dual SGLT1/SGLT2 inhibitor, improved glycemic control in patients with type 2 diabetes in a randomized, placebo-controlled trial. Clin Pharmacol Ther. 2012;92(2):158–69.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Buse JB, Garg SK, Rosenstock J, et al. Sotagliflozin in combination with optimized insulin therapy in adults with type 1 diabetes: the North American inTandem1 study. Diabetes Care. 2018;41(9):1970–80.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Danne T, Cariou B, Banks P, et al. HbA1c and hypoglycemia reductions at 24 and 52 weeks with sotagliflozin in combination with insulin in adults with type 1 diabetes: the European inTandem2 study. Diabetes Care. 2018;41(9):1981–90.

    Article  CAS  PubMed  Google Scholar 

  14. Garg SK, Henry RR, Banks P, et al. Effects of sotagliflozin added to insulin in patients with type 1 diabetes. N Engl J Med. 2017;377(24):2337–48.

    Article  CAS  PubMed  Google Scholar 

  15. Danne T, Cariou B, Buse JB, et al. Improved time in range and glycemic variability with sotagliflozin in combination with insulin in adults with type 1 diabetes: a pooled analysis of 24-week continuous glucose monitoring data from the inTandem program. Diabetes Care. 2019;42(5):919–30.

    Article  CAS  PubMed  Google Scholar 

  16. Baker C, Wason S, Banks P, et al. A 12-week dose-ranging study of sotagliflozin, a dual SGLT1 and SGLT2 inhibitor, as adjunct therapy to insulin in type 1 diabetes (inTandem4) [abstract no. 884]. Diabetologia. 2017;60(Suppl. 1):S409.

    Google Scholar 

  17. Sands AT, Zambrowicz BP, Rosenstock J, et al. Sotagliflozin, a dual SGLT1 and SGLT2 inhibitor, as adjunct therapy to insulin in type 1 diabetes. Diabetes Care. 2015;38(7):1181–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Bode B, Banks P, Sawhney S, et al. Efficacy and safety of sotagliflozin, a dual SGLT1 and SGLT2 inhibitor, as adjunct to insulin in young adults with poorly controlled type 1 diabetes (JDRF Study) [abstract no. 186]. Diabetologia. 2017;60(Suppl. 1):S87–8.

    Google Scholar 

  19. Rosenstock J, Cefalu WT, Lapuerta P, et al. Greater dose-ranging effects on A1C levels than on glucosuria with LX4211, a dual inhibitor of SGLT1 and SGLT2, in patients with type 2 diabetes on metformin monotherapy. Diabetes Care. 2015;38(3):431–8.

    Article  CAS  PubMed  Google Scholar 

  20. Zambrowicz B, Lapuerta P, Strumph P, et al. LX4211 therapy reduces postprandial glucose levels in patients with type 2 diabetes mellitus and renal impairment despite low urinary glucose excretion. Clin Ther. 2015;37(1):71–82.e12.

    Article  CAS  PubMed  Google Scholar 

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    Anthony Markham & Susan J Keam

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  1. Anthony Markham
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  2. Susan J Keam
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Correspondence to Anthony Markham.

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The preparation of this review was not supported by any external funding.

Conflict of interest

During the peer review process the manufacturer of the agent under review was offered an opportunity to comment on the article. Changes resulting from any comments received were made by the authors on the basis of scientific completeness and accuracy. A. Markham, a contracted employee of Adis International Ltd/Springer Nature, and Susan Keam, a salaried employee of Adis International Ltd/Springer Nature, are responsible for the article content and declare no relevant conflicts of interest.

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This profile has been extracted and modified from the AdisInsight database. AdisInsight tracks drug development worldwide through the entire development process, from discovery, through pre-clinical and clinical studies to market launch and beyond.

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Markham, A., Keam, S.J. Sotagliflozin: First Global Approval. Drugs 79, 1023–1029 (2019). https://doi.org/10.1007/s40265-019-01146-5

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