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Drug Res (Stuttg) 2016; 66(07): 345-350
DOI: 10.1055/s-0035-1569454
Original Article
© Georg Thieme Verlag KG Stuttgart · New York

Ipragliflozin as an Initial Therapy in Drug Naïve Subjects with Type 2 Diabetes

E. Kutoh
1   Department of Clinical Research, Biomedical Center, Tokyo, Japan
2   Division of Diabetes and Metabolism, Department of Internal Medicine, Gyoda General Hospital, Saitama, Japan
3   Division of Diabetes and Endocrinology, Department of Internal Medicine, Higashitotsuka Memorial Hospital, Yokohama, Japan
,
A. Wada
2   Division of Diabetes and Metabolism, Department of Internal Medicine, Gyoda General Hospital, Saitama, Japan
,
T. Murayama
1   Department of Clinical Research, Biomedical Center, Tokyo, Japan
,
M. Hirate
1   Department of Clinical Research, Biomedical Center, Tokyo, Japan
› Author Affiliations
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Publication History

Publication Date:
07 April 2016 (online)

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Abstract

Objectives: The aim of this study is to investigate ipragliflozin as an initial type 2 diabetes (T2DM) drug.

Methods: Ipragliflozin 25–50 mg/day monotherapy was performed with drug naïve subjects with T2DM (n=31). As a comparator, 12.5–25 mg/day alogliptin monotherapy was undertaken (n=32). At 3 months, levels of metabolic parameters were compared with those at baseline.

Findings: 4 subjects discontinued ipragliflozin due to intolerance or adverse events, while none dropped out with alogliptin. At 3 months, similar decreases of HbA1c levels were observed with these 2 drugs (10.21–8.31%, p<0.00001, with ipragliflozin, and 10.08–8.25%, p<0.00001, with alogliptin), however fasting blood glucose (FBG) levels decreased with significant inter-group differences (− 23.5% with iprgliflozin and – 10.8% with alogliptin). While similar increases of homeostasis model assessment (HOMA)-B levels were observed with these 2 drugs, HOMA-R levels significantly decreased only with ipragliflozin (−19.4%, p<0.02). Un-correlative link between HOMA-R and HOMA-B levels at baseline became significantly correlative (R=0.6017, p<0.001) only with ipragliflozin. Significant reductions of body mass index (BMI, −2.6%, P<0.05) were observed with ipragliflozin, however, no correlations between the changes of BMI and those of HbA1c or FBG were noted.

Conclusions: These results suggest that ipragliflozin has good glycemic efficacy as an initial therapy in subjects with T2DM, although certain adverse events or tolerability issues are concerned. It improves insulin sensitivity and may restore the impaired beta-cell function. However body weight reduction with ipragliflozin is not associated with its glycemic efficacy.

Key words

SGLT-2 inhibitors - ipragliflozin - initial therapy - insulin resistance - beta-cell function
 

  • References

  • 1 Inzucchi SE, Bergenstal RM, Buse JB et al. Management-of hyperglycaemia-in-type 2 diabetes, 2015: a patient-centred approach. Update to a position statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetologia. 2015 58. 429-442
    PubMedGoogle Scholar
  • 2 Inzucchi SE, Bergenstal RM, Buse JB et al. Management of hyperglycemia in type 2 diabetes, 2015: a patient-centered approach: update to a position statement of the American Diabetes Association and the European Association for the Study of Diabetes. Diabetes Care 2015; 38: 140-149
    CrossrefPubMedGoogle Scholar
  • 3 Goldman-Levine JD. Combination therapy when metformin is not an option for type 2 diabetes. Ann Pharmacother 2015; 49: 688-699
    CrossrefPubMedGoogle Scholar
  • 4 Abdul-Ghani MA, Norton L, Defronzo RA. Role of sodium-glucose cotransporter 2 (SGLT 2) inhibitors in the treatment of type 2 diabetes. Endocr Rev 2011; 32: 515-531
    CrossrefPubMedGoogle Scholar
  • 5 Whalen K, Miller S, Onge ES. The role of sodium-glucose co-transporter 2 inhibitors in the treatment of type 2 diabetes. ClinTher 2015; 37: 1150-1166
    PubMedGoogle Scholar
  • 6 Scheen AJ, Paquot N. Metabolic effects of SGLT-2 inhibitors beyond increased glucosuria: A review of the clinical evidence. Diabetes Metab 2014; 40 (Suppl. 01) S4-S11
    CrossrefPubMedGoogle Scholar
  • 7 Takahara M, Shiraiwa T, Matsuoka TA et al. Ameliorated pancreatic β cell dysfunction in type 2 diabetic patients treated with a sodium-glucose cotransporter 2 inhibitor ipragliflozin. Endocr J 2015; 62: 77-86
    CrossrefPubMedGoogle Scholar
  • 8 Halimi S, Vergès B. Adverse effects and safety of SGLT-2 inhibitors. Diabetes Metab 2014; 40 (Suppl. 01) S28-S34
    CrossrefPubMedGoogle Scholar
  • 9 Tahrani AA. SGLT-2 inhibitors as second-line therapy in type 2 diabetes. Lancet Diabetes Endocrinol 2014; 2: 678-679
    PubMedGoogle Scholar
  • 10 Garber AJ, Abrahamson MJ, Barzilay JI et al. AACE/ACE Comprehensive Diabetes Management Algorithm 2015. Endocr Pract 2015; 21: 438-447
    CrossrefPubMedGoogle Scholar
  • 11 Hedrington MS, Davis SN. Ipragliflozin, a sodium-glucose cotransporter 2 inhibitor, in the treatment of type 2 diabetes. Expert Opin Drug Metab Toxicol 2015; 11: 613-623
    CrossrefPubMedGoogle Scholar
  • 12 Kurosaki E, Ogasawara H. Ipragliflozin and other sodium-glucose cotransporter-2 (SGLT2) inhibitors in the treatment of type 2 diabetes: preclinical and clinical data. Pharmacol Ther 2013; 139: 51-59
    CrossrefPubMedGoogle Scholar
  • 13 Committee of the Japan Diabetes Society on the diagnostic criteria of diabetes mellitus. Report of the committee on the classification and diagnostic criteria of diabetes mellitus J Diabetes Investig 2010; 1: 212-228
    CrossrefPubMed
  • 14 Ma Y, Olendzki BC, Merriam PA et al. A randomized clinical trial comparing low-glycemic index versus ADA dietary education among individuals with type 2 diabetes. Nutrition 2008; 24: 45-56
    CrossrefPubMedGoogle Scholar
  • 15 Little RR, Rohlfing CL, Wiedmeyer HM et al. NGSP Steering Committee. The national glycohemoglobin standardization program: a five-year progress report. Clin Chem. 2001 47. 1985-1992
    PubMedGoogle Scholar
  • 16 Miedema K. Towards worldwide standardisation of HbA1c determination. Diabetologia 2004; 47: 1143-1148
    CrossrefPubMedGoogle Scholar
  • 17 Kutoh E, Hirate M, Wada A. Distinct glucose-lowering properties in good responders treated with sitagliptin and alogliptin. Int J Clin Pract 2015; 69: 1296-1302
    CrossrefPubMedGoogle Scholar
  • 18 Matthews DR, Hosker JP, Rudenski AS et al. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 1985; 28: 412-419
    Google Scholar
  • 19 Kutoh E, Fukushima T. Insulin-dependent actions of pioglitazone in newly diagnosed, drug naïve patients with type 2 diabetes. Endocrine 2009; 35: 333-340
    CrossrefPubMedGoogle Scholar
  • 20 Kutoh E, Hori T. Effect of Pioglitazone on Serum Uric Acid Levels in Newly Diagnosed, Drug-Naïve Patients with Type 2 Diabetes. Endocr Res 2013; 38: 151-159
    CrossrefPubMedGoogle Scholar
  • 21 Kutoh E, Ukai Y. Alogliptin as an initial therapy in patients with newly diagnosed, drug naïve type 2 diabetes: a randomized, control trial. Endocrine 2012; 41: 435-441
    CrossrefPubMedGoogle Scholar
  • 22 Kutoh E, Kaneoka N, Hirate M. Alogliptin: a new dipeptidyl peptidase-4 inhibitor with potential anti-atherogenic properties. Endocr Res 2015; 40: 88-96
    CrossrefPubMedGoogle Scholar
  • 23 Kutoh E, Hirate M, Ikeno Y. Teneligliptin as an initial therapy for newly diagnosed, drug naive subjects with type 2 diabetes. J Clin Med Res 2014; 6: 287-294
    PubMedGoogle Scholar
  • 24 Leahy JL. Natural history of beta-cell dysfunction in NIDDM. Diabetes Care 1990; 13: 992-1010
    CrossrefPubMedGoogle Scholar
  • 25 Brunton SA. The potential role of sodium glucose co-transporter 2 inhibitors in the early treatment of type 2 diabetes mellitus. Int J Clin Pract 2015; 69: 1071-1087
    CrossrefPubMedGoogle Scholar
  • 26 Yokono M, Takasu T, Hayashizaki Y et al. SGLT2 selective inhibitor ipragliflozin reduces body fat mass by increasing fatty acid oxidation in high-fat diet-induced obese rats. Eur J Pharmacol 2014; 727: 66-74
    CrossrefPubMedGoogle Scholar
  • 27 Mikhail N. Safety of canagliflozin in patients with type 2 diabetes. Curr Drug Saf 2014; 9: 127-132
    CrossrefPubMedGoogle Scholar
  • 28 Vivian EM. Dapagliflozin: a new sodium-glucose cotransporter 2 inhibitor for treatment of type 2 diabetes. Am J Health Syst Pharm 2015; 72: 361-372
    CrossrefPubMedGoogle Scholar
  • 29 https://www.invokanahcp.com/prescribing-information.pdf
    PubMed
  • 30 Sakurai H. Urate transporters in the genomic era. Curr Opin Nephrol Hypertens 2013; 22: 545-550
    CrossrefPubMedGoogle Scholar
  • 31 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: 2117-2128
    CrossrefPubMedGoogle Scholar