Benefit of Early Add-on of Linagliptin to Insulin in Japanese Patients With Type 2 Diabetes Mellitus: Randomized-Controlled Open-Label Trial (TRUST2).

INTRODUCTION: This trial was conducted to assess the long-term safety, efficacy, and benefit of early add-on of linagliptin to insulin in patients with type 2 diabetes mellitus (T2DM). METHODS: This trial enrolled 246 subjects. The subjects were randomized to the linagliptin group or the control group and were observed for 156 weeks. After week 16, subjects in the control group were also allowed to add linagliptin to evaluate the benefit of early add-on of linagliptin to insulin. The primary end point was a change in HbA1c from baseline to week 16. Secondary end points included fasting plasma glucose, daily insulin dose, and frequency of adverse events. RESULTS: HbA1c and fasting plasma glucose levels significantly decreased from baseline to week 16 in the linagliptin group compared with the control group. The significant improvement in HbA1c continued until week 52. The daily insulin dose significantly decreased in the linagliptin group compared with the control group. The frequency of hypoglycemia and adverse events was comparable in both groups. CONCLUSIONS: Add-on of linagliptin to insulin was tolerated, improved glycemic control, and reduced the daily insulin dose. This study demonstrates the long-term safety, efficacy and benefit of early add-on of linagliptin to insulin in Japanese T2DM patients.

Insulin degludec is associated with less frequent and milder hypoglycemia in insulin-deficient patients with type 1 diabetes compared with insulin glargine or detemir.

INTRODUCTION: The aim of this study was to determine the efficacy of insulin degludec (IDeg) relative to insulin glargine (IGlar) or insulin detemir (IDet) in glycemic control, as evaluated by continuous glucose monitoring (CGM) in insulin-deficient patients with type 1 diabetes. METHODS: We studied 28 outpatients treated with IGlar or IDet (IGlar/IDet). Basal insulin was switched to IDeg when glycemic control was considered unstable, as judged by the dawn phenomenon or nocturnal hypoglycemia. Whole-day CGM data were also divided into daytime and nighttime data. RESULTS: The dawn phenomenon or nocturnal hypoglycemia under IGlar/IDet treatment was observed in all patients. Among 26 patients who completed the study, there were no significant differences in parameters representing glycemic variability, hyperglycemia, mean glycemic control, and HbA1c or insulin therapy-related quality of life at the night score. Measures of hypoglycemia [whole-day %Low and area under the curve (AUC) below 70] were significantly lower under IDeg treatment than under IGlar/IDet treatment (%Low, 9.6 ± 11.5 vs. 14.7 ± 14.9%, p = 0.045; AUC below 70, 85.5 ± 126.0 vs. 145.0 ± 178.6 mg/dl h, p = 0.030). Dividing patients into two groups according to percentage or degree of hypoglycemia under IGlar/IDet treatment, the whole-day, daytime and nighttime %Low in the high-percentage groups and AUC below 70 in the high-degree groups were significantly ameliorated, respectively (p < 0.05). CONCLUSION: Patients with unstable glycemic control under IGlar/IDet treatment did not improve glycemic control upon switching to IDeg, but the frequency and the degree of hypoglycemia was reduced in insulin-deficient outpatients with type 1 diabetes, especially in those suffering from severe hypoglycemia.

Coefficient of variation of R-R interval closely correlates with glycemic variability assessed by continuous glucose monitoring in insulin-depleted patients with type 1 diabetes.

AIMS: In type 1 diabetic patients, insulin secretory capacity, meals and physical activity correlate with glycemic variability. Autonomic function associated with gastrointestinal motility and counterregulatory hormone secretion is another candidate which correlates with glucose variability. The aim of this study is to clarify a new clinical parameter associated with glycemic variability in insulin-depleted patients with type 1 diabetes. METHODS: We studied 31 inpatients with type 1 diabetes. We evaluated glycemic variability calculated by continuous glucose monitoring, clinical parameters and the coefficient of variation of R-R interval (CVR-R). Glycemic variability was also assessed during the daytime and nighttime. RESULTS: The CVR-R showed a significant negative correlation with the whole-day standard deviation (SD) (r = -0.50, p = 0.007), mean amplitude of glycemic excursions (MAGE) (r = -0.47, p=0.011), M-value (r = -0.38, p = 0.048) and mean of daily differences (MODD) (r = -0.59, p = 0.001). The CVR-R also showed a significant negative correlation with the nighttime SD (r = -0.59, p = 0.001), MAGE (r = -0.47, p=0.011), M-value (r = -0.53, p = 0.004) and MODD (r = -0.65, p = 0.0003). And furthermore, the CVR-R also showed a significant negative correlation with the daytime SD (r = -0.44, p = 0.019) and MAGE (r = -0.50, p = 0.006), but not with the daytime M-value or MODD. The nighttime SD was significantly higher in patients with diabetic polyneuropathy than in patients without it (p = 0.016), while the CVR-R was significantly lower in patients with polyneuropathy than in patients without it (p = 0.009). CONCLUSIONS: CVR-R is closely correlated with glycemic variability, especially during nighttime, in insulin-depleted patients with type 1 diabetes. Measuring CVR-R may help us to presume the degree of glycemic variability in those patients.