Effects of a sodium glucose co‐transporter 2 selective inhibitor, ipragliflozin, on the diurnal profile of plasma glucose in patients with type 2 diabetes: A study using continuous glucose monitoring

Abstract

Aims/IntroductionTo assess the effects of sodium glucose co-transporter 2 inhibitor therapy on the pathophysiology of type 2 diabetes.Materials and MethodsWe administered ipragliflozin to 21 inpatients with type 2 diabetes for 7 days, and analyzed the diurnal profiles of plasma glucose and 3-hydroxybutyrate. A total of 21 age-, sex- and body mass index-matched diabetic patients served as controls.ResultsContinuous glucose monitoring showed that the 24-h glucose curve was shifted downward without hypoglycemia by the administration of ipragliflozin. The average glucose level was reduced from 182 ± 54 mg/dL to 141 ± 33 mg/dL (P < 0.0001). The magnitude of the reduction was highly correlated with the baseline average glucose level. Homeostasis model assessment of insulin resistance was decreased, and homeostasis model assessment of β-cell function was increased during the treatment. Urinary glucose excretion was correlated with the average glucose level both on day 0 and on day 7, although the regression line was steeper and shifted leftward on day 7. The ipragliflozin-treated patients lost more weight than the control patients (1.4 ± 0.5 vs 0.5 ± 0.6 kg, P < 0.0001). Plasma levels of 3-hydroxybutyrate were significantly increased with peaks before breakfast and before dinner. Patient age and bodyweight loss were negatively and positively correlated with the peak levels of 3-hydroxybutyrate on day 7, respectively.ConclusionsThe ipragliflozin treatment improved the 24-h glucose curve without causing hypoglycemia. The close correlation between the magnitude of glucose reduction and the baseline plasma glucose concentration suggests that the risk of hypoglycemia is likely low. It might be prudent to monitor ketone body levels in younger patients and in patients with rapid weight loss.

Comparative study of the effects of ipragliflozin and sitagliptin on multiple metabolic variables in Japanese patients with type 2 diabetes: A multicentre, randomized, prospective, open‐label, active‐controlled study

“…The HOMA‐β values increased and PI/I ratio decreased in the sitagliptin group compared with the ipragliflozin group. Recent reports have shown that 7‐day or 4‐week treatments with ipragliflozin improved β‐cell function, assessed by HOMA‐β and the disposition index during 75‐g oral glucose tolerance test, respectively . In the present study, the HOMA‐β and PI/I ratios were unchanged after 12‐week treatment with ipragliflozin.…”

“…Recent reports have shown that 7-day or 4-week treatments with ipragliflozin improved β-cell function, assessed by HOMA-β and the disposition index during 75-g oral glucose tolerance test, respectively. 13,14 In the present study, the HOMA-β and PI/I ratios were unchanged instance, sitagliptin might be more beneficial for those with insulin secretory dysfunction and ipragliflozin for those with excessive fat and insulin resistance.…”

Metabolic and hemodynamic effects of sodium‐dependent glucose cotransporter 2 inhibitors on cardio‐renal protection in the treatment of patients with type 2 diabetes mellitus

“…Furthermore, in the Continuous Glucose Monitoring study, luseogliflozin 2.5 mg once daily for 7 days shifted the area under curve (AUC) for glucose to lower levels, and both AUC and peak glucose levels significantly reduced in patients with mildly impaired glycemic control. Similarly, Yamada et al . reported that the ipragliflozin treatment improved the entire 24‐h glucose AUC without causing hypoglycemia.…”

“…Furthermore, in the Continuous Glucose Monitoring study 27 , luseogliflozin 2.5 mg once daily for 7 days shifted the area under curve (AUC) for glucose to lower levels, and both AUC and peak glucose levels significantly reduced in patients with mildly impaired glycemic control. Similarly, Yamada et al 28 reported that the ipragliflozin treatment improved the entire 24-h glucose AUC without causing hypoglycemia. Finally, Japanese patients with type 2 diabetes inadequately controlled with sulfonylureas were randomly assigned to receive luseogliflozin 2.5 mg or a placebo for 24 weeks, and the placebo-adjusted mean reduction in HbA1c was -0.88% in the treatment group 29 .…”

Efficacy of ipragliflozin as monotherapy or as add‐on therapy with other oral antidiabetic medications for treating type 2 diabetes in Japanese patients with inadequate glycemic control: A subgroup analysis based on patient characteristics

“…Notably, the reduction in blood glucose distribution width induced by ipragliflozin suggests that ipragliflozin reduces glucose spikes, the difference between maximum plasma glucose and fasting plasma glucose levels. Although Yamada et al ,. reported that ipragliflozin simultaneously lowered preprandial and postprandial glucose excursions in patients whose HbA1c level was higher than that of the present study or in patients treated with hypoglycemia‐inducible antidiabetic medications, the improvements in glucose spikes reported seem to be lower than in the present study.…”