Sotagliflozin decreases postprandial glucose and insulin concentrations by delaying intestinal glucose absorption

Journal of Clinical Endocrinology and Metabolism

Volumn 105, Issue 4, 2020, Pages E1235-E1249

  Powell, David R ^a   Zambrowicz, Brian ^a   Morrow, Linda ^b   Beysen, Carine ^b   Hompesch, Marcus ^b   Turner, Scott ^c   Hellerstein, Marc ^d   Banks, Phillip ^a   Strumph, Paul ^a,e   Lapuerta, Pablo ^a  

^a LEXICON PHARMACEUTICALS INC   (United States)

^b ProSciento Inc   (United States)

^c Pliant Therapeutics   (United States)

^d UNIVERSITY OF CALIFORNIA   (United States)

^e Metavant Sciences   (United States)

Author keywords

Intestinal glucose absorption; Postprandial glucose; SGLT1 inhibitor; SGLT2 inhibitor; Sotagliflozin; Type 2 diabetes

Indexed keywords

CANAGLIFLOZIN; GLUCOSE; INSULIN; PLACEBO; SOTAGLIFLOZIN; (2S,3R,4R,5S,6R)-2-(4-CHLORO-3-(4-ETHOXYBENZYL)PHENYL)-6-(METHYLTHIO)TETRAHYDRO-2H-PYRAN-3,4,5-TRIOL; BIOLOGICAL MARKER; GLYCOSIDE; GLYCOSYLATED HEMOGLOBIN; HEMOGLOBIN A1C PROTEIN, HUMAN;

ADULT; AREA UNDER THE CURVE; ARTICLE; COHORT ANALYSIS; CONTROLLED STUDY; CROSSOVER PROCEDURE; DOUBLE BLIND PROCEDURE; DRUG METABOLISM; FEMALE; GLUCOSE ABSORPTION; GLUCOSE BLOOD LEVEL; GLUCOSE INFUSION; HUMAN; HUMAN EXPERIMENT; INSULIN BLOOD LEVEL; INTESTINE ABSORPTION; MALE; MEAL; NORMAL HUMAN; PRIORITY JOURNAL; SINGLE DRUG DOSE; STANDARDIZATION; CLINICAL TRIAL; DRUG EFFECT; FOLLOW UP; INSULIN DEPENDENT DIABETES MELLITUS; INTESTINE MUCOSA; METABOLISM; NON INSULIN DEPENDENT DIABETES MELLITUS; PATHOLOGY; POSTPRANDIAL STATE; PROGNOSIS; RANDOMIZED CONTROLLED TRIAL; BLOOD PRESSURE; BODY MASS; DRUG ABSORPTION; ELECTROCARDIOGRAPHY; ENZYME LINKED IMMUNOSORBENT ASSAY; HEART RATE; KIDNEY FUNCTION; LIVER FUNCTION; MASS FRAGMENTOGRAPHY;

ADULT; BIOMARKERS; BLOOD GLUCOSE; CROSS-OVER STUDIES; DIABETES MELLITUS, TYPE 1; DIABETES MELLITUS, TYPE 2; DOUBLE-BLIND METHOD; FEMALE; FOLLOW-UP STUDIES; GLYCATED HEMOGLOBIN A; GLYCOSIDES; HUMANS; INSULIN; INTESTINAL ABSORPTION; INTESTINAL MUCOSA; MALE; POSTPRANDIAL PERIOD; PROGNOSIS; SODIUM-GLUCOSE TRANSPORTER 2 INHIBITORS;

EID: 85081945865     PISSN: 0021972X     EISSN: 19457197     Source Type: Journal    
DOI: 10.1210/clinem/dgz258     Document Type: Article

References (44)

1. Ghezzi C, Hirayama BA, Gorraitz E, Loo DD, Liang Y, Wright EM. SGLT2 inhibitors act from the extracellular surface of the cell membrane. Physiol Rep. 2014;2(6):e12058.
2. Wright EM, Loo DD, Hirayama BA. Biology of human sodium glucose transporters. Physiol Rev. 2011;91(2):733-794.
3. Mudaliar S, Polidori D, Zambrowicz B, Henry RR. Sodium-glucose cotransporter inhibitors: effects on renal and intestinal glucose transport: from bench to bedside. Diabetes Care. 2015;38(12):2344-2353.
4. Musso G, Gambino R, Cassader M, Pagano G. A novel approach to control hyperglycemia in type 2 diabetes: sodium glucose co-transport (SGLT) inhibitors: systematic review and meta-analysis of randomized trials. Ann Med. 2012;44(4):375-393.
5. Neal B, Perkovic V, Mahaffey KW, et al.; CANVAS Program Collaborative Group. Canagliflozin and cardiovascular and renal events in type 2 diabetes. N Engl J Med. 2017;377(7):644-657.
6. Zinman B, Wanner C, Lachin JM, et al.; EMPA-REG OUTCOME Investigators. Empagliflozin, cardiovascular outcomes, and mortality in Type 2 diabetes. N Engl J Med. 2015;373(22):2117-2128.
7. Perkovic V, de Zeeuw D, Mahaffey KW, et al. Canagliflozin and renal outcomes in type 2 diabetes: results from the CANVAS Program randomised clinical trials. Lancet Diabetes Endocrinol. 2018;6(9):691-704.
8. Wanner C, Inzucchi SE, Lachin JM, et al.; EMPA-REG OUTCOME Investigators. Empagliflozin and progression of kidney disease in Type 2 diabetes. N Engl J Med. 2016;375(4):323-334.
9. 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):1970-1980.
10. Dandona P, Mathieu C, Phillip M, et al.; DEPICT-1 Investigators. Efficacy and safety of dapagliflozin in patients with inadequately controlled type 1 diabetes: the DEPICT-1 52-week study. Diabetes Care. 2018;41(12):2552-2559.
11. Danne T, Biester T, Kordonouri O. Combined SGLT1 and SGLT2 inhibitors and their role in diabetes care. Diabetes Technol Ther. 2018;20(S2):S269-S277.
12. 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):1981-1990.
13. 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):2337-2348.
14. Garg SK, Strumph P. Effects of sotagliflozin added to insulin in type 1 diabetes. N Engl J Med. 2018;378(10):967-968.
15. Mathieu C, Dandona P, Gillard P, et al.; DEPICT-2 Investigators. Efficacy and safety of dapagliflozin in patients with inadequately controlled type 1 diabetes (the DEPICT-2 Study): 24-week results from a randomized controlled trial. Diabetes Care. 2018;41(9):1938-1946.
16. Rosenstock J, Marquard J, Laffel LM, et al. Empagliflozin as adjunctive to insulin therapy in type 1 diabetes: the EASE trials. Diabetes Care. 2018;41(12):2560-2569.
17. 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):919-930.
18. 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):158-169.
19. 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):1181-1188.
20. 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):232-242.
21. 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):250-259.
22. Zambrowicz B, Ding ZM, Ogbaa I, et al. Effects of LX4211, a dual SGLT1/SGLT2 inhibitor, plus sitagliptin on postprandial active GLP-1 and glycemic control in type 2 diabetes. Clin Ther. 2013;35(3):273-285.e7.
23. Polidori D, Sha S, Mudaliar S, et al. Canagliflozin lowers postprandial glucose and insulin by delaying intestinal glucose absorption in addition to increasing urinary glucose excretion: results of a randomized, placebo-controlled study. Diabetes Care. 2013;36(8):2154-2161.
24. Sha S, Devineni D, Ghosh A, et al. Canagliflozin, a novel inhibitor of sodium glucose co-transporter 2, dose dependently reduces calculated renal threshold for glucose excretion and increases urinary glucose excretion in healthy subjects. Diabetes Obes Metab. 2011;13(7):669-672.
25. Sha S, Polidori D, Farrell K, et al. Pharmacodynamic differences between canagliflozin and dapagliflozin: results of a randomized, double-blind, crossover study. Diabetes Obes Metab. 2015;17(2):188-197.
26. Stein P, Berg JK, Morrow L, et al. Canagliflozin, a sodium glucose co-transporter 2 inhibitor, reduces post-meal glucose excursion in patients with type 2 diabetes by a non-renal mechanism: results of a randomized trial. Metabolism. 2014;63(10):1296-1303.
27. Steele R, Bjerknes C, Rathgeb I, Altszuler N. Glucose uptake and production during the oral glucose tolerance test. Diabetes. 1968;17(7):415-421.
28. Baker C, Wason S, Banks P, et al. Dose-dependent glycometabolic effects of sotagliflozin on type 1 diabetes over 12 weeks: the inTandem4 trial. Diabetes Obes Metab. 2019;21(11):2440-2449.
29. Monnier L, Colette C, Dejager S, Owens D. Residual dysglycemia when at target HbA(1c) of 7% (53mmol/mol) in persons with type 2 diabetes. Diabetes Res Clin Pract. 2014;104(3):370-375.
30. Monnier L, Colette C, Dejager S, Owens DR. Near normal HbA1c with stable glucose homeostasis: the ultimate target/aim of diabetes therapy. Rev Endocr Metab Disord. 2016;17(1):91-101.
31. Runge AS, Kennedy L, Brown AS, et al. Does time-in-range matter? Perspectives from people with diabetes on the success of current therapies and the drivers of improved outcomes. Clin Diabetes. 2018;36(2):112-119.
32. Beck RW, Bergenstal RM, Riddlesworth TD, et al. Validation of time in range as an outcome measure for diabetes clinical trials. Diabetes Care. 2019;42(3):400-405.
33. Lu J, Ma X, Zhou J, et al. Association of time in range, as assessed by continuous glucose monitoring, with diabetic retinopathy in type 2 diabetes. Diabetes Care. 2018;41(11):2370-2376.
34. Polidori D, Mari A, Ferrannini E. Canagliflozin, a sodium glucose co-transporter 2 inhibitor, improves model-based indices of beta cell function in patients with type 2 diabetes. Diabetologia. 2014;57(5):891-901.
35. Seidelmann SB, Feofanova E, Yu B, et al. Genetic variants in SGLT1, glucose tolerance, and cardiometabolic risk. J Am Coll Cardiol. 2018;72(15):1763-1773.
36. Dobbins RL, Greenway FL, Chen L, et al. Selective sodium-dependent glucose transporter 1 inhibitors block glucose absorption and impair glucose-dependent insulinotropic peptide release. Am J Physiol Gastrointest Liver Physiol. 2015;308(11):G946-G954.
37. Goodwin NC, Ding ZM, Harrison BA, et al. Discovery of LX2761, a sodium-dependent glucose cotransporter 1 (SGLT1) inhibitor restricted to the intestinal lumen, for the treatment of diabetes. J Med Chem. 2017;60(2):710-721.
38. Powell DR, Smith MG, Doree DD, et al. LX2761, a sodium/glucose cotransporter 1 inhibitor restricted to the intestine, improves glycemic control in mice. J Pharmacol Exp Ther. 2017;362(1):85-97.
39. Shibazaki T, Tomae M, Ishikawa-Takemura Y, et al. KGA-2727, a novel selective inhibitor of a high-affinity sodium glucose cotransporter (SGLT1), exhibits antidiabetic efficacy in rodent models. J Pharmacol Exp Ther. 2012;342(2):288-296.
40. Powell DR, DaCosta CM, Gay J, et al. Improved glycemic control in mice lacking Sglt1 and Sglt2. Am J Physiol Endocrinol Metab. 2013;304(2):E117-E130.
41. Merovci A, Solis-Herrera C, Daniele G, et al. Dapagliflozin improves muscle insulin sensitivity but enhances endogenous glucose production. J Clin Invest. 2014;124(2):509-514.
42. Ferrannini E, Muscelli E, Frascerra S, et al. Metabolic response to sodium-glucose cotransporter 2 inhibition in type 2 diabetic patients. J Clin Invest. 2014;124(2):499-508.
43. Martinez R, Al-Jobori H, Ali AM, et al. Endogenous glucose production and hormonal changes in response to canagliflozin and liraglutide combination therapy. Diabetes. 2018;67(6):1182-1189.
44. Center for Drug Evaluation and Research, U.S. Food and Drug Administration. FDA Introductory Remarks. 2019. Available at: https://www.fda.gov/media/121289/download. Accessed November 15, 2019.