Efficacy and safety of teneligliptin in addition to insulin therapy in type 2 diabetes mellitus patients on hemodialysis evaluated by continuous glucose monitoring

https://doi.org/10.1016/j.diabres.2016.10.016Get rights and content

Highlights

  • Twenty-one type 2 DM patients on HD treated with insulin were enrolled.

  • CGM was performed, and insulin was reduced after teneligliptin administration.

  • Insulin dose was reduced to one third, mean and SD of BG level did not change.

  • On the HD day, minimum BG level was significantly elevated.

  • Teneligliptin may reduce total daily insulin dose and prevent hypoglycemic event.

Abstract

Aims

Appropriate glycemic control without hypoglycemia is important in patients with type 2 diabetes on hemodialysis. Teneligliptin, a novel dipeptidyl peptidase-4 inhibitor, can be used without dose adjustment for these patients. Using continuous glucose monitoring (CGM), we evaluated the efficacy and safety of adding teneligliptin to insulin therapy.

Methods

Twenty-one type 2 diabetes mellitus patients on hemodialysis treated with insulin were enrolled. After the adjustment of insulin dose, their blood glucose level was monitored by CGM. Insulin dose was reduced after teneligliptin administration.

Results

The median total daily insulin dose significantly reduced from 18 (9–24) U to 6 (0–14) U (p < 0.0001). Maximum, mean, and standard deviation of blood glucose level on the hemodialysis and non-hemodialysis days did not change after teneligliptin administration. However, minimum blood glucose level was significantly elevated on the hemodialysis day after teneligliptin administration (from 3.9 ± 1.0 mmol/L to 4.4 ± 0.9 mmol/L, p = 0.040). The incidence of asymptomatic hypoglycemia on the hemodialysis day detected by CGM significantly decreased from 38.1% to 19.0% (p = 0.049).

Conclusions

Teneligliptin may contribute toward reducing the total daily insulin dose and preventing hypoglycemic events on the hemodialysis day in type 2 diabetes mellitus patients.

Introduction

Diabetic nephropathy is a leading cause of end-stage renal disease (ESRD) in developed countries [1], [2]. Recent studies have suggested that poor glycemic control is associated with higher mortality in diabetes mellitus (DM) patients on hemodialysis (HD) [3], [4], [5]. These patients are at a high risk of life-threatening hypoglycemia [6], which is associated with an increased risk of cardiovascular events, hospitalization, and mortality [7]. Therefore, appropriate glycemic control without harmful hypoglycemia is required in this population.

Dipeptidyl peptidase-4 (DPP-4) inhibitors have recently been introduced as promising oral anti-diabetic drugs and are expected to improve glycemic control with a low risk of hypoglycemia and weight gain [8]. Teneligliptin, a novel DPP-4 inhibitor, can be used for glycemic control without dose adjustment for treating type 2 DM patients on HD. A few studies have reported that teneligliptin monotherapy can improve glycemic control without hypoglycemia in DM patients on HD [9], [10]. However, the efficacy and safety of a combination therapy comprising teneligliptin and insulin are unknown. Thus, in this study, we used continuous glucose monitoring (CGM) to evaluate the efficacy and safety of adding teneligliptin to insulin therapy in type 2 DM patients on HD.

Section snippets

Patients

Twenty-one insulin-treated type 2 DM patients on HD who were observed at the outpatient clinic of Matsunami General Hospital between September 2014 and August 2015 were recruited for this study and followed up for 24 weeks. Type 1 DM patients were excluded. All patients underwent regular HD three times a week with a high-flux membrane and standard bicarbonate dialysate that contained 7.0 mmol/L of glucose.

This study adhered to the principles of the Declaration of Helsinki, and all patients

Clinical and laboratory characteristics at baseline

The clinical characteristics of all patients (N = 21) are summarized in Table 1. All patients were initially treated with only insulin (8 insulin lispro, 4 insulin lispro with insulin glargine, 7 insulin lispro with insulin degludec, and 2 insulin glargine).

Insulin dose before and after teneligliptin administration

In all patients, there were reductions of 0–4 U/day in the doses of long-acting insulin (insulin glargine and insulin degludec) and 2–4 U/immediately before each meal in the doses of rapid-acting insulin (insulin lispro) when teneligliptin was

Discussion

Blood glucose control in DM patients on HD is very difficult. Hypoglycemia frequently occurs in DM patients with ESRD because of the loss of dietary intake, decrease in renal gluconeogenesis, decrease in insulin clearance, and decrease in metabolism and clearance of drugs [6]. Glycemic fluctuations are greater on HD days, and this may also lead to an increase in the risk of hypoglycemia [12], [13]. In the present study, CGM was used to evaluate the pattern of blood glucose fluctuation.

Before

Conclusion

Teneligliptin may reduce the total daily dose of insulin and prevent hypoglycemic events on the HD day in type 2 DM patients on HD.

Conflicts of interest

None.

References (26)

  • H. Otsuki et al.

    Safety and efficacy of teneligliptin: a novel DPP-4 inhibitor for hemodialysis patients with type 2 diabetes

    Int Urol Nephrol

    (2014)
  • Japanese Society for Dialysis Therapy

    Management of diabetic patients on hemodialysis 2012

    J Jpn Soc Dial Ther

    (2013)
  • H.S. Jung et al.

    Analysis of hemodialysis-associated hypoglycemia in patients with type 2 diabetes using a continuous glucose monitoring system

    Diabetes Technol Ther

    (2010)
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