Comparison of efficacy and safety of insulin degludec/liraglutide and insulin glargine U-100/lixisenatide in individuals with type 2 diabetes mellitus using professional continuous glucose monitoring.

AIM/INTRODUCTION: Insulin glargine U100/lixisenatide and insulin degludec/liraglutide are fixed-ratio combinations containing basal insulin and a glucagon-like peptide-1 receptor agonist capable of reducing both fasting and postprandial blood glucose levels with a single formulation. This study aimed to compare the time in range (TIR) and the time below range (TBR) level 1 using professional continuous glucose monitoring and to establish criteria for the differential use of the fixed-ratio combinations. MATERIALS AND METHODS: Thirty-six outpatients with type 2 diabetes mellitus (24 men and 12 women; average age, 62.1 years) were randomly assigned to the groups. At 0 and 18 weeks, a device was worn to compare the TIR and TBR level 1. The correlation between the C-peptide index at baseline and TIR at 18 weeks was assessed. RESULTS: The TIR and TBR level 1 showed no significant differences between the two groups. Both groups showed significant positive correlations between the C-peptide index and the TIR (P = 0.002, r = 0.679; P = 0.002, r = 0.681, respectively). The changes in glycemic variability, therapeutic indices, and body mass index were not significantly different among the groups (P > 0.05). The receiver operating curve analysis revealed that the cut-off values of the C-peptide index to achieve TIR of >70% at 18 weeks were 1.258 (sensitivity, 77.8%; specificity, 100%) and 1.099 (sensitivity, 57.1%; specificity, 90.9%) in the insulin glargine U100/lixisenatide and insulin degludec/liraglutide groups, respectively. CONCLUSIONS: A TIR of >70% was achieved for both fixed-ratio combinations without significant differences.

Efficacy of IDegLira Versus IDegAsp Therapy in Patients with Type 2 Diabetes: A Randomized Crossover Study by isCGM.

INTRODUCTION: We aimed to compare the efficacy of insulin degludec/insulin aspart (IDegAsp) and insulin degludec/liraglutide (IDegLira) in controlling glucose fluctuation and suppressing postprandial glucose levels using intermittently scanned continuous glucose monitoring. METHODS: Twenty-four patients with type 2 diabetes mellitus were randomly allocated to receive either IDegLira or IDegAsp followed by IDegAsp or IDegLira, respectively. A crossover study was conducted with intermittently scanned continuous glucose monitoring. We compared the postprandial blood glucose level, time in range, and time below range from a 3-day intermittently scanned continuous glucose monitoring period for each treatment group. RESULTS: The time in range was significantly higher in IDegLira than in IDegAsp. Postprandial glucose levels 90 and 120 min after breakfast and 60, 90, and 120 min after lunch were significantly lower for IDegLira than for IDegAsp. However, postprandial glucose levels 90 and 120 min after supper were significantly lower for IDegAsp than for IDegLira. There was no significant difference in the time below range between IDegLira and IDegAsp. CONCLUSION: IDegLira was more effective in treating type 2 diabetes mellitus than IDegAsp, as indicated by a higher time in range and lower postprandial glucose level at breakfast and lunch. This study was registered with the University Hospital Medical Information Network Clinical Trial Registry (UMIN 000039221).

Comparisons of efficacy and safety in insulin glargine and lixisenatide plus glulisine combination therapy with multiple daily injection therapy in Japanese patients with type 2 diabetes.

AIMS/INTRODUCTION: Multiple daily injection therapy for early glycemic control in patients with type 2 diabetes mellitus is associated with hypoglycemia and weight gain. This study aimed to compare the efficacy (time in range of glucose level 70-180 mg/dL), safety (time below range level 1 of glucose <70 mg/dL), glycemic variability changes, therapeutic indices, body mass index and titration periods between multiple daily injection and insulin glargine U100 and lixisenatide (iGlarLixi) combination (iGlarLixi + insulin glulisine; injected once daily [evenings]) therapies using intermittent continuous glucose monitoring. MATERIALS AND METHODS: A total of 40 hospitalized patients with type 2 diabetes were randomly assigned to the iGlarLixi + insulin glulisine group or the multiple daily injection group. An intermittent continuous glucose monitoring system was attached, and each injection was adjusted to achieve the target glucose level according to the respective titration algorithm. Times in and below the range were analyzed using data collected on days 11-13 of the intermittent continuous glucose monitoring. RESULTS: The time in range did not significantly differ between the groups. However, the time below range level 1 was lower in the iGlarLixi + insulin glulisine group (P = 0.047). The changes in glycemic variability, therapeutic indices and body mass index were not significantly different between the groups, although the titration period was significantly shorter in the iGlarLixi + insulin glulisine group (P = 0.033). CONCLUSIONS: iGlarLixi + insulin glulisine combination therapy is safe and equally efficacious as multiple daily injection therapy for glycemic control, while avoiding hypoglycemia risk and reducing the number of injections are required.

Efficacy and Safety of Tofogliflozin and Ipragliflozin for Patients with Type-2 Diabetes: A Randomized Crossover Study by Flash Glucose Monitoring.

INTRODUCTION: Sodium-glucose cotransporter 2 (SGLT2) inhibitors promote urinary glucose excretion. However, the differences in the effects of various SGLT2 inhibitors are unknown. We used flash glucose monitoring (FGM) to identify the differences between tofogliflozin and ipragliflozin in terms of efficacy in reducing glycemic variability and mitigate hypoglycemia risk. METHODS: In this crossover study, 24 patients with type-2 diabetes mellitus (T2DM) receiving insulin glargine U300 therapy were randomly allocated to tofogliflozin and ipragliflozin or ipragliflozin and tofogliflozin group. Glycemic variability and hypoglycemia were compared using to the 3-day FGM data per treatment period. RESULTS: Glucose level 2 h after each meal was significantly lower with tofogliflozin administration than with ipragliflozin administration. Time below the target glucose range after tofogliflozin administration was significantly lower than that after ipragliflozin administration (2.1% ± 4.4% vs. 8.7% ± 11.7%). The 24-h standard deviation of glucose level, mean amplitude of glycemic excursion, and mean percent time with nocturnal hypoglycemia after tofogliflozin administration were significantly lower than those after ipragliflozin administration. CONCLUSIONS: Tofogliflozin was more effective and safer than ipragliflozin in reducing glycemic variability and mitigating hypoglycemia risk in patients with T2DM treated with insulin glargine U300. TRIAL REGISTRATION: This trial was registered at the University Hospital Medical Information Network Clinical Trial Registry (no. UMIN000037158).

Differential Effect of Hypoalbuminemia on Hypoglycemia on Type 2 Diabetes Patients Treated with Insulin Glargine 300 U/ml and Insulin Degludec.

INTRODUCTION: Hypoglycemia resulting from insulin therapy for treatment of diabetes increases the risk of adverse cardiovascular events. Determining biomarkers that provide accurate estimation of hypoglycemia risk may allow for more accurate patient management and care. The purpose of this study was to determine the cutoff value of serum albumin (s-alb) that increases the risk of hypoglycemia in patients treated with insulin degludec. METHODS: This study used a crossover design and randomized 30 patients admitted for glycemic control to compare differences between insulin glargine 300 U/ml (Gla300) and degludec treatments. RESULTS: The cutoff value of s-alb associated with 24-h hypoglycemia and nocturnal hypoglycemia in patients treated with degludec was 3.8 g/dl. In patients with s-alb levels < 3.8 g/dl, mean percentages of time with hypoglycemia, clinically important hypoglycemia, and nocturnal hypoglycemia were significantly lower in those treated with Gla300 compared with patients treated with degludec. CONCLUSION: This study identified a cutoff value for s-alb levels that indicates risk of hypoglycemia in patients treated with degludec. Monitoring s-alb levels in patients treated with degludec will help to mitigate the risk of hypoglycemia. TRIAL REGISTRATION: University Hospital Medical Information Network (UMIN 000031044).

Comparison of the efficacy and safety of insulin degludec/aspart (twice-daily injections), insulin glargine 300 U/mL, and insulin glulisine (basal-bolus therapy).

AIMS/INTRODUCTION: We compared the efficacy and safety of insulin degludec/aspart (IDegAsp) twice-daily injections with insulin glargine 300 U/mL and insulin glulisine basal-bolus therapy (Gla300/Glu) using insulin glargine 300 U/mL (Gla300) and insulin glulisine (Glu). MATERIALS AND METHODS: A total of 20 patients with type 2 diabetes mellitus were treated with IDegAsp twice-daily injections; achievement of target preprandial glucose concentration of 100-130 mg/dL at breakfast and supper was determined using a wearable flash glucose monitoring system. Patients were later switched to Gla300/Glu basal-bolus therapy before breakfast and before supper. Data were collected on days 2-4 and days 12-14 for each treatment period. The study's primary efficacy end-point was the mean percentage of time with a target glucose range of 70-180 mg/dL, and safety end-points were the mean percentage of time with hypoglycemia having glucose levels <70 mg/dL, clinically important hypoglycemia with glucose levels <54 mg/dL and nocturnal (00.00-06.00) hypoglycemia. RESULTS: Considering efficacy, the mean percentage of time for the target glucose range of IDegAsp was significantly lower than that of Gla300/Glu (73.1 [69.4-81.1] vs 84.2 [80.2-93.1], P = 0.001). Considering safety, the mean percentages of hypoglycemia (<70 mg/dL; 2.1 [0.0-9.4] vs 14.4 [4.4-22.3]), clinically important hypoglycemia (<54 mg/dL; 0.0 [0.0-0.2] vs 1.9 [0.0-5.6]) and nocturnal (00.00-06.00 hours) hypoglycemia (0.5 [0.0-5.9] vs 8.9 [3.1-11.8]) of Gla300/Glu were significantly lower than those of IDegAsp (P = 0.012, 0.036 and 0.007, respectively). CONCLUSIONS: When compared with the IDegAsp twice-daily injections, Gla300/Glu basal-bolus therapy might achieve more effective glycemic control without hypoglycemic risk.

Efficacy and safety of insulin glargine 300 U/mL vs insulin degludec in patients with type 2 diabetes: A randomized, open-label, cross-over study using continuous glucose monitoring profiles.

AIMS/INTRODUCTION: Compared with glargine 100 U/mL (Gla100), glargine 300 U/mL (Gla300) and degludec (Deg) - the ultralong-acting insulins - reportedly have more stable effects and reduce the risk of hypoglycemia. Currently, they are considered to be the most useful basal insulins. The present study aimed to compare the efficacy and safety of Gla300 and Deg on glycemic control using continuous glucose monitoring. MATERIALS AND METHODS: In this single-center, open-label, parallel-group, two-period, cross-over study, 30 patients with type 2 diabetes were randomized to once-daily Gla300 followed by Deg with the same units (n = 15) or vice versa (n = 15). The primary end-points of this study were the mean percentage of time within the target glucose range of 70-180 mg/dL as efficacy and hypoglycemia of <70 mg/dL as safety indicators, as measured using continuous glucose monitoring during each treatment period. RESULTS: The mean percentage of time within the target glucose range was not different between Gla300 and Deg (77.8 ± 19.2 vs 76.9 ± 18.3%, P = 0.848). However, the mean percentage of time of hypoglycemia with Gla300 was significantly lower than that of Deg (1.3 ± 2.7 vs 5.5 ± 6.4%, P = 0.002). In the secondary safety end-points, the mean percentage of time of severe hypoglycemia (<54 mg/dL) or nocturnal hypoglycemia with Gla300 was also significantly lower than that of Deg. CONCLUSIONS: The present study showed the comparable efficacy of Gla300 and Deg on glycemic control; however, the risk of hypoglycemia was markedly lower for Gla300 than for Deg.

Improved glycemic control with teneligliptin in patients with type 2 diabetes mellitus on hemodialysis: Evaluation by continuous glucose monitoring.

AIMS: Recent reports suggest that appropriate glycemic control without hypoglycemia could decrease mortality in patients with diabetes mellitus (DM) and end-stage renal disease (ESRD). However, an indication of oral anti-diabetic drugs is limited in this population. The aim of this study was to evaluate efficacy of teneligliptin, a novel DPP-4 inhibitor, by continuous glucose monitoring (CGM) in patients with type 2 DM (T2DM) on hemodialysis (HD). METHODS: This 4-week, open label, single arm, intervention trial included 10 diabetic patients undergoing HD and with glycated albumin (GA) level of ≥18.3%. Teneligliptin treatment was administered on days with HD sessions (HD day) and on days without HD sessions (NHD day); blood glucose values were measured by CGM. The primary endpoint was improvement of glycemic control evaluated by area under the curve (AUC). As secondary endpoints, changes in GA, HbA1c and fasting plasma glucose (FPG) were evaluated. RESULTS: Teneligliptin improved blood glucose AUC on both HD days (p=0.004), and NHD days (p=0.004). This was accompanied by a significant reduction in GA, HbA1c, and FPG, without severe hypoglycemia. CONCLUSIONS: Teneligliptin is one of the useful options for glycemic control in T2DM patients undergoing HD.