A novel and selective sodium-glucose cotransporter-2 inhibitor, tofogliflozin, improves glycaemic control and lowers body weight in patients with type 2 diabetes mellitus

Diabetes, Obesity and Metabolism

Volumn 17, Issue 10, 2015, Pages 984-993

  Ikeda, S ^a   Takano, Y ^a   Cynshi, O ^a   Tanaka, R ^a   Christ, A D ^b   Boerlin, V ^b   Beyer, U ^b   Beck, A ^b   Ciorciaro, C ^b   Meyer, M ^b   Kadowaki, T ^c  

^a CHUGAI PHARMACEUTICAL CO LTD   (Japan)

^b F HOFFMANN LA ROCHE LTD   (Switzerland)

^c UNIVERSITY OF TOKYO   (Japan)

Author keywords

Drug development; Phase I II study; SGLT2 inhibitor; Type 2 diabetes

Indexed keywords

3 HYDROXYBUTYRIC ACID; ADIPONECTIN; CREATININE; GLUCOSE; HEMOGLOBIN A1C; KETONE BODY; MAGNESIUM; METFORMIN; PLACEBO; TOFOGLIFLOZIN; UREA; URIC ACID; 6-((4-ETHYLPHENYL)METHYL)-3',4',5',6'-TETRAHYDRO-6'-(HYDROXYMETHYL)SPIRO(ISOBENZOFURAN-1(3H),2'-(2H)PYRAN)-3',4',5'-TRIOL; ANTIDIABETIC AGENT; BENZHYDRYL DERIVATIVE; GLUCOSE BLOOD LEVEL; GLUCOSIDE; GLYCOSYLATED HEMOGLOBIN; HEMOGLOBIN A1C PROTEIN, HUMAN; KETONE;

ADD ON THERAPY; ADULT; AGED; ANALYTICAL PARAMETERS; ARTICLE; BACKACHE; BLOOD PRESSURE MEASUREMENT; BODY WEIGHT; CARDIOVASCULAR DISEASE; CEREBROVASCULAR DISEASE; CONSTIPATION; CONTROLLED STUDY; CREATININE BLOOD LEVEL; DIASTOLIC BLOOD PRESSURE; DIET; DIZZINESS; DOSE RESPONSE; DOUBLE BLIND PROCEDURE; DRUG EFFICACY; DRUG SAFETY; DRUG TOLERABILITY; DRUG WITHDRAWAL; EXERCISE; FEMALE; GLUCOSE BLOOD LEVEL; GLUCOSE INTOLERANCE; GLUCOSE URINE LEVEL; GLYCEMIC CONTROL; HEADACHE; HEMATOCRIT; HEMOGLOBIN BLOOD LEVEL; HUMAN; HYPERGLYCEMIA; HYPOGLYCEMIA; INCIDENCE; KETONE BODY RATIO; KIDNEY DISEASE; MAGNESIUM BLOOD LEVEL; MAJOR CLINICAL STUDY; MALE; MONOTHERAPY; MULTICENTER STUDY; MUSCULOSKELETAL PAIN; NAUSEA; NON INSULIN DEPENDENT DIABETES MELLITUS; PHASE 2 CLINICAL TRIAL; POLLAKISURIA; POLYURIA; PROSTATE CANCER; PROTEIN BLOOD LEVEL; RANDOMIZED CONTROLLED TRIAL; RHINOPHARYNGITIS; SYSTOLIC BLOOD PRESSURE; TOOTH PAIN; UREA NITROGEN BLOOD LEVEL; URIC ACID BLOOD LEVEL; URINARY TRACT INFECTION; UROGENITAL TRACT INFECTION; VISUAL ANALOG SCALE; VOMITING; WEIGHT REDUCTION; BLOOD; BLOOD PRESSURE; CHEMICALLY INDUCED; CLINICAL TRIAL; COMBINATION DRUG THERAPY; DIABETES MELLITUS, TYPE 2; DIABETIC DIET; DIET RESTRICTION; DRUG EFFECTS; GLUCOSURIA; KINESIOTHERAPY; METABOLISM; MIDDLE AGED; MULTIMODALITY CANCER THERAPY; URINE;

ADULT; AGED; BENZHYDRYL COMPOUNDS; BLOOD GLUCOSE; BLOOD PRESSURE; BODY WEIGHT; COMBINED MODALITY THERAPY; DIABETES MELLITUS, TYPE 2; DIET, DIABETIC; DOSE-RESPONSE RELATIONSHIP, DRUG; DOUBLE-BLIND METHOD; DRUG THERAPY, COMBINATION; EXERCISE THERAPY; FASTING; FEMALE; GLUCOSIDES; GLYCOSURIA; HEMOGLOBIN A, GLYCOSYLATED; HUMANS; HYPOGLYCEMIC AGENTS; KETONES; MALE; METFORMIN; MIDDLE AGED;

EID: 84942258962     PISSN: 14628902     EISSN: 14631326     Source Type: Journal    
DOI: 10.1111/dom.12538     Document Type: Article

References (26)

1. Mitrakou A. Kidney: its impact on glucose homeostasis and hormonal regulation. Diabetes Res Clin Pract 2011; 93: S66-72.
2. Chao EC, Henry RR. SGLT2 inhibition-a novel strategy for diabetes treatment. Nat Rev Drug Discov 2010; 9: 551-559.
3. Rahmoune H, Thompson PW, Ward JM, Smith CD, Hong G, Brown J. Glucose transporters in human renal proximal tubular cells isolated from the urine of patients with non-insulin-dependent diabetes. Diabetes 2005; 54: 3427-3434.
4. Freitas HS, Anhê GF, Melo KF etal. Na(+) -glucose transporter-2 messenger ribonucleic acid expression in kidney of diabetic rats correlates with glycemic levels: involvement of hepatocyte nuclear factor-1alpha expression and activity. Endocrinology 2008; 149: 717-724.
5. DeFronzo RA, Davidson JA, Del Prato S. The role of the kidneys in glucose homeostasis: a new path towards normalizing glycaemia. Diabetes Obes Metab 2012; 14: 5-14.
6. Wright EM, Loo DD, Hirayama BA. Biology of human sodium glucose transporters. Physiol Rev 2011; 91: 733-794.
7. Banerjee SK, McGaffin KR, Pastor-Soler NM, Ahmad F. SGLT1 is a novel cardiac glucose transporter that is perturbed in disease states. Cardiovasc Res 2009; 84: 111-118.
8. Yu AS, Hirayama BA, Timbol G etal. Functional expression of SGLTs in rat brain. Am J Physiol Cell Physiol 2010; 299: C1277-1284.
9. Komoroski B, Vachharajani N, Feng Y, Li L, Kornhauser D, Pfister M. Dapagliflozin, a novel, selective SGLT2 inhibitor, improved glycemic control over 2 weeks in patients with type 2 diabetes mellitus. Clin Pharmacol Ther 2009; 85: 513-519.
10. Sha S, Devineni D, Ghosh A etal. 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: 669-672.
11. Heise T, Seewaldt-Becker E, Macha S etal. Safety, tolerability, pharmacokinetics and pharmacodynamics following 4 weeks' treatment with empagliflozin once daily in patients with type 2 diabetes. Diabetes Obes Metab 2013; 15: 613-621.
12. Rieg T, Masuda T, Gerasimova M etal. Increase in SGLT1-mediated transport explains renal glucose reabsorption during genetic and pharmacologic SGLT2 inhibition in euglycemia. Am J Physiol Renal Physiol 2014; 306: F188-193.
13. Ohtake Y, Sato T, Kobayashi T etal. Discovery of tofogliflozin, a novel C-arylglucoside with an O-spiroketal ring system, as a highly selective sodium glucose cotransporter 2 (SGLT2) inhibitor for the treatment of type 2 diabetes. J Med Chem 2012; 55: 7828-7840.
14. Suzuki M, Honda K, Fukazawa M etal. Tofogliflozin, a potent and highly specific sodium/glucose cotransporter 2 inhibitor, improves glycemic control in diabetic rats and mice. J Pharmacol Exp Ther 2012; 341: 692-701.
15. Ferrannini E, Ramos SJ, Salsali A, Tang W, List JF. Dapagliflozin monotherapy in type 2 diabetic patients with inadequate glycemic control by diet and exercise: a randomized, double-blind, placebo-controlled, phase 3 trial. Diabetes Care 2010; 33: 2217-2224.
16. Bailey CJ, Gross JL, Pieters A, Bastien A, List JF. Effect of dapagliflozin in patients with type 2 diabetes who have inadequate glycaemic control with metformin: a randomised, double-blind, placebo-controlled trial. Lancet 2010; 375: 2223-2233.
17. Stenlöf K, Cefalu WT, Kim KA etal. Efficacy and safety of canagliflozin monotherapy in subjects with type 2 diabetes mellitus inadequately controlled with diet and exercise. Diabetes Obes Metab 2013; 15: 372-382.
18. Lavalle-González FJ, Januszewicz A, Davidson J etal. Efficacy and safety of canagliflozin compared with placebo and sitagliptin in patients with type 2 diabetes on background metformin monotherapy: a randomised trial. Diabetologia 2013; 56: 2582-2592.
19. Bolinder J, Ljunggren Ö, Kullberg J etal. Effects of dapagliflozin on body weight, total fat mass, and regional adipose tissue distribution in patients with type 2 diabetes mellitus with inadequate glycemic control on metformin. J Clin Endocrinol Metab 2012; 97: 1020-1031.
20. Nagata T, Fukazawa M, Honda K etal. Selective SGLT2 inhibition by tofogliflozin reduces renal glucose reabsorption under hyperglycemic but not under hypo- or euglycemic conditions in rats. Am J Physiol Endocrinol Metab 2013; 304: E414-423.
21. Ferrannini E, Muscelli E, Frascerra S etal. Metabolic response to sodium-glucose transporter 2 (SGLT2) inhibition in patients with type 2 diabetes. J Clin Invest 2014; 124: 499-508.
22. Smulders RA, Leeflang S, Schliess F, Jax T, Kurosaki E, Kadokura T. The effect of ipragliflozin on the total glucose turnover after OGTT in healthy subjects and patients with type 2 diabetes mellitus [abstract 997]. Presented at the 49th Annual Meeting of the European Association for the Study of Diabetes (EASD), Barcelona, 23-27 September 2013.
23. Merovci A, Solis-Herrera C, Daniele G etal. Dapagliflozin improves muscle insulin sensitivity but enhances endogenous glucose production. J Clin Invest 2014; 124: 509-514.
24. Wilding JP, Woo V, Rohwedder K, Sugg J, Parikh S, for the Dapagliflozin 006 Study Group. Dapagliflozin in patients with type 2 diabetes receiving high doses of insulin: efficacy and safety over 2 years. Diabetes Obes Metab 2014; 16: 124-136.
25. Stenlöf K, Cefalu WT, Kim KA etal. Long-term efficacy and safety of canagliflozin monotherapy in patients with type 2 diabetes inadequately controlled with diet and exercise: findings from the 52-week CANTATA-M study. Curr Med Res Opin 2014; 30: 163-175.
26. Ferrannini E, Berk A, Hantel S etal. Long-term safety and efficacy of empagliflozin, sitagliptin, and metformin: an active-controlled, parallel-group, randomized, 78-week open-label extension study in patients with type 2 diabetes. Diabetes Care 2013; 36: 4015-4021.