Comparison of the effects of gemigliptin and dapagliflozin on glycaemic variability in type 2 diabetes: A randomized, open‐label, active‐controlled, 12‐week study (STABLE II study)

Abstract

Aims The aim of this study was to compare the effect of gemigliptin, a dipeptidyl peptidase‐4 inhibitor, and dapagliflozin, a sodium glucose co‐transporter‐2 inhibitor, on glycaemic variability in type 2 diabetes patients. Materials and methods In this randomized, blinded end point, multicentre clinical trial, we enrolled 71 patients with type 2 diabetes who were inadequately controlled with metformin alone or were drug naïve. The participants were randomized to receive gemigliptin 50 mg (n = 35) or dapagliflozin 10 mg (n = 36) daily for 12 weeks. Glycaemic variability was estimated by mean amplitude of glycaemic excursions (MAGE), standard deviation (SD) and coefficient of variation (CV) using a 6‐day continuous glucose monitoring system. The primary efficacy endpoint was change in MAGE after 12 weeks compared to baseline. Results Intergroup differences in baseline characteristics were not significant. The adjusted mean change (± standard error) in MAGE after 12 weeks in the gemigliptin and dapagliflozin groups was −27.2 ± 4.4 mg/dL and −7.9 ± 4.9 mg/dL, respectively. Between‐group comparisons showed a significantly larger reduction in MAGE in the gemigliptin group (−19.2 mg/dL; 95% CI, −31.3 to −7.2; P = .002). Measures of SD and CV also showed a significantly larger reduction in the gemigliptin group. Average glycaemic control, estimated by HbA1c, fasting glucose and safety profiles, was comparable between the two groups. Conclusions Compared to dapagliflozin, gemigliptin significantly improved glycaemic variability, with similar glucose‐lowering efficacy and safety profiles in patients with type 2 diabetes who were inadequately controlled with metformin alone or were drug naïve.

Effects of DPP-4 Inhibitors on Blood Glucose Variability in Japanese Patients with Type 2 Diabetes on Maintenance Hemodialysis: A Prospective Observational Exploratory Study

“…Also, our data from the linear mixed-effects model showed a rapid BG drop during hemodialysis and a tendency for hypoglycemia in the subsequent nighttime period in maintenance hemodialysis patients with type 2 diabetes. Although DPP-4 inhibitors have been shown to improve BG variability in patients with type 2 diabetes in many randomized controlled trials (RCTs) [41][42][43][44][45][46][47][48][49] (see the table in the Electronic supplementary material), few studies have reported the same effect in maintenance hemodialysis patients [50]. Our study illustrates the usefulness of DPP-4 inhibitors in these patients.…”

“…The ability of DPP-4 inhibitors to suppress BG variability in patients with type 2 diabetes has been shown in studies using CGM [51, 52]. Furthermore, several RCTs using CGM found that BG variability is suppressed more effectively by DPP-4 inhibitors than by other agents such as sulfonylureas [41,42] and sodium glucose cotransporter 2 inhibitors [43][44][45] [41,49], or had used metformin only [41][42][43]46]. There have also been some reports on the usefulness of DPP-4 inhibitors in patients on hemodialysis [50], but none has shown obvious suppression of BG variability.…”

“…Furthermore, several RCTs using CGM found that BG variability is suppressed more effectively by DPP-4 inhibitors than by other agents such as sulfonylureas [ 41 , 42 ] and sodium glucose cotransporter 2 inhibitors [ 43 – 45 ] or by combination with insulin therapy [ 46 – 49 ]. The patients in these RCTs who showed suppressed BG variability with DPP-4 inhibitors had a mean age of less than 60 years [ 42 – 44 , 46 , 48 , 49 ], had HbA1c > 7% [ 41 – 44 , 46 – 49 ], were drug naïve [ 41 , 49 ], or had used metformin only [ 41 – 43 , 46 ]. There have also been some reports on the usefulness of DPP-4 inhibitors in patients on hemodialysis [ 50 ], but none has shown obvious suppression of BG variability.…”

“…The reduction in prandial glucagon is believed to be the most important mechanism through which DPP-4 inhibitors improve the BG wave [ 35 ]. The present study showed that DPP-4 inhibitors are as effective in dialysis patients as in type 2 diabetes patients not undergoing hemodialysis [ 41 , 44 , 48 ]. The mechanisms are unclear, and more detailed studies are needed, including those that analyze the fluctuation in glucagon.…”

Time in Range from Continuous Glucose Monitoring: A Novel Metric for Glycemic Control

“…Diabetes Metab J 2020;44:828-839 https://e-dmj.org vidual short-term glycemic status for determining the efficacy and safety of new drugs and devices, comparing drugs in improving glycemic status, or evaluating the correlation with chronic diabetic complications [30,33,[49][50][51]. When using real-time CGM, the patient can modify behavior such as diet, exercise, medication, or insulin dose in response to real-time changing data, which can affect the outcome of the study [52,53].…”