Numerous drugs with different mechanisms of action and different pharmacologic profiles are being used with the aim of improving glycemic control in patients with type 2 diabetes. Therapeutic options for patients with type 2 diabetes and chronic kidney disease (CKD) are limited because a reduced glomerular filtration rate results in the accumulation of certain drugs and/or their metabolites. Conventional oral hypoglycemic agents, such as sulfonylurea (SU), are not suitable due to the risk of prolonged hypoglycemia; furthermore, metformin is contraindicated for moderate to advanced CKD. Therefore, in order to achieve good glycemic control, insulin injection therapy remains the mainstay of treatment in diabetic patients with moderate to advanced CKD, particularly in those receiving dialysis therapy. However, some agents have been used even in patients with CKD. Repaglinide and mitiglinide are rapid- and short-acting insulinotropic SU receptor ligands. They are rarely accompanied by hypoglycemia, and are attractive therapeutic options even in the dialysis population. In addition, alpha-glucosidase inhibitors are rarely accompanied by hypoglycemia and are administered without dose adjustments in dialysis patients. However, the National Kidney Foundation Kidney Disease Outcomes Quality Initiative guidelines recommended that alpha-glucosidase inhibitors should be avoided in patients with advanced stage CKD and on dialysis. Furthermore, mitiglinide is not currently used in the US. Thus, recommended oral antidiabetic agents differ between countries. Moreover, dipeptidyl peptidase-4 inhibitors and incretin mimetics are new antihyperglycemic agents, which may be used more frequently in the future in patients with type 2 diabetes and CKD. Here, we describe the pharmacokinetics, metabolism, clinical efficacy, and safety of oral Antidiabetic agents for patients with CKD, including those receiving dialysis.

In patients with diabetes receiving chronic haemodialysis, both very high and low glucose levels are associated with poor outcomes, including mortality. Conditions that are associated with an increased risk of hypoglycaemia in these patients include decreased gluconeogenesis in the remnant kidneys, deranged metabolic pathways, inadequate nutrition, decreased insulin clearance, glucose loss to the dialysate and diffusion of glucose into erythrocytes during haemodialysis. Haemodialysis-induced hypoglycaemia is common during treatments with glucose-free dialysate, which engenders a catabolic status similar to fasting; this state can also occur with 5.55 mmol/l glucose-containing dialysate. Haemodialysis-induced hypoglycaemia occurs more frequently in patients with diabetes than in those without. Insulin therapy and oral hypoglycaemic agents should, therefore, be used with caution in patients on dialysis. Several hours after completion of haemodialysis treatment a paradoxical rebound hyperglycaemia may occur via a similar mechanism as the Somogyi effect, together with insulin resistance. Appropriate glycaemic control tailored for patients on haemodialysis is needed to avoid haemodialysis-induced hypoglycaemia and other glycaemic disarrays. In this Review we summarize the pathophysiology and current management of glycaemic disarrays in patients on haemodialysis.

The annual survey of the Japanese Society for Dialysis Therapy Renal Data Registry (JRDR) was sent to 4458 dialysis facilities at the end of 2018; among these facilities, 4402 facilities (98.7%) responded to the facility questionnaire, and 4222 (94.7%) responded to the patient questionnaire. The number of chronic dialysis patients in Japan continues to increase every year; as of the end of 2018, it had reached 339,841 patients, representing 2688 patients per million population. Among the prevalent dialysis patients, the mean age was 68.75 years, and diabetic nephropathy was the most common primary disease among the prevalent dialysis patients (39.0%), followed by chronic glomerulonephritis (26.8%) and nephrosclerosis (10.8%). The number of incident dialysis patients was 40, 468, and a reduction by 491 from 2017. The mean age of the incident dialysis patients was 69.99 years old. Diabetic nephropathy was also the most common primary disease (42.3%), representing a 0.2 percent point reduction from 2017. The distribution of diabetic nephropathy appears to have reached a plateau. The number of deceased patients during 2018 was 33,863, and the crude annual death rate was 10.0%. Heart failure was the most common cause of death (23.5%), followed by infection (21.3%) and malignant tumor (8.4%); these causes were similar to

No abstract

Numerous drugs with different mechanisms of action are currently in use with the aim of improving glycemic control, and drugs with different pharmacologic profiles are employed in the management of type 2 diabetes. Therapeutic options for patients with type 2 diabetes and end-stage renal disease (ESRD) are, however, limited because the reduced glomerular filtration rate results in the accumulation of certain drugs and/ or their metabolites [1]. Conventional oral hypoglyce- Abstract. The potent and selective dipeptidyl peptidase-4 inhibitor vildagliptin improves glycemic control in patients with type 2 diabetes through incretin hormone-mediated increases in both α-and β-cell responsiveness to glucose. We conducted a prospective, open-label, parallel group, controlled study of 51 patients with type 2 diabetic patients undergoing hemodialysis (HD) during the 24-week study period. Patients were assigned to two groups: the vildagliptin group (n = 30) and the control group (n = 21). Vildagliptin was administered at 50 mg/day for the first 8 weeks. Then doses were titrated by dose-doubling to a maximum of 100 mg/day if hemoglobin A1c (HbA1c) or glycated albumin (GA) target levels had not been reached. No vildagliptin was administered to the controls. The average final dose of vildagliptin was 80 ± 5 mg daily. After 24 weeks, vildagliptin had decreased average HbA1c levels from 6.7 % baseline to 6.1 %, average GA levels from 24.5 % baseline to 20.5 % and average postprandial plasma glucose levels from 186 mg/dL baseline to 140 mg/dL (all p < 0.0001). In the control group, we observed no such changes. Vildagliptin efficacy did not differ according to age or body mass index, but the GA reduction was significantly greater in the anti-diabetic agents-naïve group. Furthermore, in patients with higher baseline GA levels, a higher vildagliptin dosage was required to produce a noticeable effect. No serious adverse effects such as hypoglycemia or liver impairment were observed in any patient. Vildagliptin was effective as a treatment for diabetic patients undergoing HD.