Effect of 24-week treatment with ipragliflozin on proinsulin/C-peptide ratio in Japanese patients with type 2 diabetes

Expert Opin Pharmacother. 2017 Jan;18(1):13-17. doi: 10.1080/14656566.2016.1261110. Epub 2016 Nov 21.

Abstract

Background: Chronic hyperglycemia has an adverse influence on beta-cell function, which is known as 'glucotoxicity'. Sodium-glucose cotransporter-2 (SGLT2) inhibitors lower the blood glucose concentration by enhancing urinary glucose excretion. This study was performed to clarify the influence of the SGLT2 inhibitor ipragliflozin on beta-cell function assessed from the plasma intact proinsulin/C-peptide ratio in Japanese patients with type 2 diabetes.

Research design and methods: This was a 24-week, prospective, single-center, open-label, single-arm study. The subjects were 19 Japanese patients with type 2 diabetes. After a 4- to 8-week period of lifestyle modification, ipragliflozin (50 mg/d) was added to their existing treatment. At baseline and at 12 and 24 weeks after starting ipragliflozin treatment, a meal test was performed to evaluate the fasting and 2-hour proinsulin/C-peptide ratio.

Results: After 24 weeks, the body mass index, fasting plasma glucose, and hemoglobin A1c were all decreased significantly. Both the fasting and 2-hour proinsulin/C-peptide ratio decreased significantly from 25.0 ± 18.9 × 10-3 to 14.3 ± 9.0 × 10-3 and from 23.2 ± 14.9 × 10-3 to 13.7 ± 5.4 × 10-3, respectively (both p < 0.01 vs. baseline).

Conclusions: These findings indicate that ipragliflozin might have a beneficial effect on beta-cells.

Keywords: Beta-cell function; Japanese; ipragliflozin; proinsulin/C-peptide ratio; sodium glucose cotransporter 2 inhibitors; type 2 diabetes.

Publication types

  • Clinical Trial

MeSH terms

  • Adult
  • Blood Glucose / drug effects
  • C-Peptide / metabolism
  • Diabetes Mellitus, Type 2 / drug therapy*
  • Female
  • Glucose / metabolism
  • Glucosides / therapeutic use*
  • Glycated Hemoglobin / analysis
  • Humans
  • Hyperglycemia / drug therapy
  • Hypoglycemic Agents / therapeutic use*
  • Insulin-Secreting Cells / drug effects
  • Male
  • Middle Aged
  • Proinsulin / metabolism
  • Prospective Studies
  • Sodium-Glucose Transporter 2
  • Sodium-Glucose Transporter 2 Inhibitors
  • Thiophenes / therapeutic use*

Substances

  • Blood Glucose
  • C-Peptide
  • Glucosides
  • Glycated Hemoglobin A
  • Hypoglycemic Agents
  • SLC5A2 protein, human
  • Sodium-Glucose Transporter 2
  • Sodium-Glucose Transporter 2 Inhibitors
  • Thiophenes
  • ipragliflozin
  • Proinsulin
  • Glucose