Gla-300 Group Research Articles

Effects of insulin glargine U300 versus insulin degludec U100 on glycemic variability, hypoglycemia, and diet evaluated by continuous glucose monitoring in type 1 diabetes: a retrospective cross-sectional study.

The impacts of insulin degludec U100 (Deg-100) and insulin glargine U300 (Gla-300) on glycemic variability (GV) in patients with type 1 diabetes, as well as the impact of major nutrient components on GV in these patients, remain unclear. This was an observational, cross-sectional, retrospective study. Type 1 diabetes mellitus patients treated with either Deg-100 or Gla-300 as basal insulin were enrolled. After the participants underwent continuous glucose monitoring, GV indices and major nutrient components were analyzed. Forty patients with type 1 diabetes were enrolled, and 20 participants used Deg-100, and 20 used Gla-300. There was no significant difference in major nutrient components between the two groups. Better GV indices of standard deviation, coefficient of variation, mean amplitude of glycemic excursion, AUCn, M-value, CONGA1, CONGA2, and CONGA4 were noted in the Gla-300 group versus Deg-100 group. Compared with patients who received once-daily injection in the morning (QD), Deg-100 administration once daily at bedtime (HS) yielded a higher low blood glucose index during both day and nocturnal periods, indicating a higher risk of hypoglycemic events. By contrast, there were significantly lower levels of CONGA1, CONGA2, and CONGA4 during insulin Gla-300 QD administration than during HS administration, indicating a lower GV of a short interval. In this real-world study involving type 1 diabetes patients, Gla-300 appears to offer more stable glucose variability than Deg-100. Administering once-daily injections could lower the risk of hypoglycemia in the Deg-100 group and minimize GV in the Gla-300 group compared to bedtime injections.

Glycaemic control, risk of hypoglycaemia and all-cause mortality in new users of second-generation basal insulin with type 2 diabetes and chronic kidney disease: a nationwide register-based cohort study.

The aim of this study was to compare the performance of the second-generation basal insulins, insulin degludec 100 U/ml (Deg-100) and insulin glargine 300 U/ml (Gla-300), in terms of change in HbA1c, hospitalisation for hypoglycaemia and all-cause mortality among individuals with type 2 diabetes and concurrent chronic kidney disease. This register-based cohort study, based on the entire Danish diabetes population, included 6519 new users of Deg-100 and Gla-300 with type 2 diabetes and moderate to end-stage chronic kidney disease. HbA1c trajectories, from initiation of either Deg-100 (2013) or Gla-300 (2015) to end of follow-up (2020), were modelled with mixed-effect models while rates of hospitalisation for hypoglycaemia and all-cause mortality were modelled in separate models using Poisson likelihood. Of the 6519 (44% women) individuals included in the study, 3747 were exposed to Deg-100 and 2772 to Gla-300. Both mean (SD) type 2 diabetes duration (14.4 [6.6] years vs 15.2 [6.7] years) and median (IQR) chronic kidney disease duration (2.3 [1.3, 3.9] years vs 2.8 [1.6, 4.6] years) were significantly shorter in the Gla-300 group. The median (IQR) follow-up time was similar between groups: 1.0 (0.5-1.6) year for Gla-300 and 1.0 (0.3-1.5) year for Deg-100. In both groups mean HbA1c levels were reduced by 13-14 mmol/mol (1.2-1.3%) from initiation to end of follow-up, with the largest reduction (of 8-9 mmol/mol [0.7-0.8%]) occurring during the first year. There was no significant difference in HbA1c reduction between Deg-100 and Gla-300. Both the rate of hospitalisation for hypoglycaemia (rate ratio 1.02 [95% CI 0.70, 1.49], Deg-100 vs Gla-300) and the rate of all-cause mortality (rate ratio 0.98 [95% CI 0.84, 1.15], Deg-100 vs Gla-300) were similar between the groups. We found no difference in HbA1c reduction, hospitalisation for hypoglycaemia or all-cause mortality between Gla-300 and Deg-100 in a real-world population of new users with type 2 diabetes and moderate to end-stage chronic kidney disease. Therefore, we conclude that these two treatment options are equally effective and safe in this vulnerable population.

84-LB: Intensification of Glucagon-Like Peptide-1 Receptor Agonists Therapy with Glargine 300 U/mL or IDegLira—The RESTORE-G Real-World Study

Combined use of basal insulin (BI) and glucagon-like peptide 1 receptor agonist (GLP1-RA) deserves consideration for the synergistic effects on glucose profile. Nevertheless, it is unclear if the addition of BI to the ongoing GLP1-RA therapy in free or fixed combination is associated with different outcomes. Aim of this RESTORE-G sub-study was to perform a propensity-score adjusted comparative effectiveness analysis of the two most innovative BIs for intensifying GLP1-RA therapy (±oral agents), i.e. Glargine 300 U/mL in free combination (Gla-300) vs. the fixed ratio combination of insulin degludec + liraglutide (IDegLira). Table shows sample sizes, patients characteristics and effectiveness results. Compared to IDegLira, Gla-300 group had older age, worse metabolic control, and higher starting BI doses. After 6 months, statistically significant larger FBG reduction and BI dose increase were found in the free vs. fixed combination group. Trends of larger HbA1c and weight reductions with the free combination were also found, without reaching the statistical significance. In conclusion, higher benefits on FBG control in free vs. fixed combination has been found in people uncontrolled on GLP-1 RA, likely due to a better titration of the components. However, inertia in insulin initiation was documented in both groups. Disclosure R. Candido: None. A. Nicolucci: Board Member; AstraZeneca, Research Support; Novo Nordisk, Sanofi, Sobi, Shionogi & Co., Ltd., AlfaSigma, Speaker's Bureau; Boehringer Ingelheim and Eli Lilly Alliance. M. Rossi: Research Support; Sanofi, Novo Nordisk, Shionogi & Co., Ltd., AlfaSigma. M. Larosa: None. R. Napoli: Advisory Panel; Sanofi, Eli Lilly and Company, Novo Nordisk, Research Support; Novo Nordisk, AstraZeneca, Speaker's Bureau; Sanofi, Eli Lilly and Company, Novo Nordisk, AstraZeneca, MSD Life Science Foundation. Restore-g study group: n/a. Funding Sanofi

Comparative effectiveness and safety of glargine 300 U/mL versus degludec 100 U/mL in insulin-naïve patients with type 2 diabetes. A multicenter retrospective real-world study (RESTORE-2 NAIVE STUDY)

AimsThis study assessed comparative effectiveness of glargine 300 U/mL (Gla-300) versus degludec 100 U/mL (Deg-100) in insulin-naïve patients with T2D.MethodsThis is a retrospective, multicenter, non-inferiority study based on electronic medical records. All patients initiating Gla-300 or Deg-100 were 1:1 propensity score-matched (PSM). Linear mixed models were used to assess the changes in continuous endpoints. Incidence rates (IR) of hypoglycemia were compared using Poisson’s regression models.ResultsNineteen centers provided data on 357 patients in each PSM cohort. HbA1c after 6 months (primary endpoint) decreased by − 1.70% (95%CI − 1.90; − 1.50) in Gla-300 group and − 169% (95%CI − 1.89; − 1.49) in Deg-100 group, confirming non-inferiority of Gla-300 versus Deg-100. Fasting blood glucose (BG) decreased by ~60 mg/dl in both groups; body weight remained unchanged. In both groups, the mean starting dose was 12U (0.15U/kg) and it was slightly titrated to 16U (0.20U/kg). IR (episodes per patient-months) of BG ≤70 mg/dl was 0.13 in Gla-300 group and 0.14 in Deg-100 group (p=0.87). IR of BG <54 mg/dL was 0.02 in both groups (p=0.49). No severe hypoglycemia occurred.ConclusionInitiating Gla-300 or Deg-100 was associated with similar improvements in glycemic control, no weight gain and low hypoglycemia rates, without severe episodes during 6 months of treatment.

Comparative effectiveness of Glargine 300 U/mL vs. Degludec 100 U/mL in patients with type 2 diabetes switching from 1° generation basal insulins

Background and aimsData on second generation basal insulin (2BI) in people with type 2 diabetes (T2D) generated by clinical trials still need confirmation in real-world clinical settings. This study aimed at assessing the comparative effectiveness of 2BI [Glargine 300 U/mL (Gla-300) vs. Degludec 100 U/mL (Deg-100)] in T2D Italian patients switching from first generation basal insulins (1BI). Methods and resultsThis was a retrospective, non-inferiority, multicenter study. Patients switching to Gla-300 or Deg-100 from 1BI were 1:1 propensity score matched (PSM). Changes during 6 months in continuous endpoints were assessed through linear mixed models. Incidence rates (IR) of hypoglycemia (episodes per patient-months) were compared using Poisson regression.Each PSM cohort included 593 patients. HbA1c decreased from baseline (8.7%) to 6 months by −0.58% (95%CI -0.69;-0.47) in Gla-300 group and −0.50% (95%CI -0.61;-0.39) in Deg-100 group, confirming the non-inferiority of Gla-300 vs. Deg-100. No between-group differences emerged: FBG was reduced by about 20 mg/dl with both 2BI, mean dose of 2BI (24.5 U, 0.3 U/Kg at the first prescription) was suboptimally titrated during 6 months (+1.34 U in Gla-300 and + 1.76 U in Deg-100), body weight showed minor changes.IR of hypoglycemia <54 mg/dl was 0.32 (95%CI 0.21; 0.49) in Gla-300 group and 0.19 (95%CI 0.11; 0.33) in Deg-100 group (p = 0.14). ConclusionIn subjects with T2D, switching to 2BI from 1BI was associated with similar improvements in glycemic control, low hypoglycemia rates and no weight gain in real-life setting. Clinical inertia, represented by late treatment intensification and suboptimal titration, represents a major issue in Italy.

Evaluation of Patient Reported Satisfaction and Clinical Efficacy of Insulin Glargine 300 U/mL Versus 100 U/mL in Patients With Type 1 Diabetes Using Flash Glucose Monitoring System.

Background and Aims:To analyze patient-reported satisfaction and clinical effectiveness of concentrated insulin glargine 300 U/mL (Gla-300) among patients with type 1 diabetes (T1D) using a flash glucose monitoring (FGM) system.Methods:This comparative study was conducted among 86 patients with T1D (aged 14-40 years), who were treated with Glargine 100 U/mL (Gla-100) and switched to Gla-300 at day 1 (baseline). The following data were collected from each patient: demographic information, clinical parameters, and glycemic control markers. All patients completed the Diabetes Treatment Satisfaction Questionnaire (Arabic version), first at baseline and then after 12 weeks. A comparison was done for all the data recorded at baseline (on Gla-100) and after 12 weeks (on Gla-300) and subjected to analysis.Results:Compared to patients treated with Gla-100, significant improvements were observed in the Gla-300 group, in terms of the ambulatory glucose profile (AGP) markers, such as percentage of time spent within the target range of the glucose levels (70-180 mg/dL) (P = .037), percentage which fell below the target (<70 mg/dL) (P = .027), and percentage of time spent (<54 mg/dL) (P = .043). Compared to Gla-100, patients treated with Gla-300 experienced significant improvements in the current treatment satisfactions (P = .047), convenient finding treatment recently (P = .034), and flexible finding treatment recently (P = .041), recommend the current treatment (P = .042) and satisfied to continue the current treatment (P = .035).Conclusion:Compared to the patients on Gla-100, patients treated with Gla-300 exhibited significant improvements in the AGP markers and degree of treatment satisfaction.

Effectiveness and Safety of Insulin Glargine 300 U/ml in Comparison with Insulin Degludec 100 U/ml Evaluated with Continuous Glucose Monitoring in Adults with Type 1 Diabetes and Suboptimal Glycemic Control in Routine Clinical Practice: The OneCARE Study.

IntroductionData regarding efficacy of second-generation basal insulins (BI) using continuous glucose monitoring (CGM) come from clinical trials. We evaluated the effectiveness of insulin glargine 300 U/ml (Gla-300) compared to insulin degludec 100 U/ml (IDeg-100) in terms of percentage of time in range (TIR); 70–180 mg/dl was obtained from CGM in sub-optimally controlled patients with type 1 diabetes (T1D) in routine clinical practice.MethodsThis observational, multicenter, cross-sectional study included patients with T1D (> 3 years diabetes duration, HbA1c ≥ 7.5%) who had switched from first-generation BI to Gla-300/IDeg-100 within the past 24 months according to physician discretion. Clinical and laboratory data were obtained from clinical records and during study visit, and CGM data were collected prior to the visit.ResultsOne hundred ninety-nine people with T1D were included [42.6 ± 13.4 (mean ± SD) years, 18.4 ± 10.4 years diabetes duration]; 104 received Gla-300, 95 IDeg-100. TIR 70–180 throughout whole day was similar in both groups, 52.4 ± 14.0 vs. 49.3 ± 13.9% Gla-300/IDeg-100, respectively. At night, TIR 70–180 and TIR 70–140 were significantly higher in the Gla-300 group compared to the IDeg-100 (52.4 vs. 46.2 and 31.8 vs. 26.9%, respectively, p = 0.0209 and p = 0.0182), and time above range (180) was significantly lower in the Gla-300 group (40.1% vs. 47.2%, p = 0.0199). Additional CGM glucometric data were comparable in both groups. Patient treatment satisfaction score assessed through the Diabetes Treatment Satisfaction Questionnaire (DTSQ) was high and similar for both insulins.ConclusionThis real-world study shows the effectiveness and safety of Gla-300 are more similar to than different from IDeg-100, with a slightly better nocturnal glucose profile, in sub-optimally controlled T1D patients switching from a first-generation BI.Supplementary InformationThe online version contains supplementary material available at 10.1007/s13300-021-01153-4.

109-LB: Comparative Effectiveness of Insulin Glargine 300 U/mL (Gla-300) and Insulin Degludec 100 U/mL (iDeg-100) in Insulin-Naïve Type 2 Diabetes Adults: RESTORE-2 Real-World Study

Second generation basal insulin (2BI) provide similar/improved efficacy with better safety compared to first generation BI. Real-world data on 2BI in patients with type 2 diabetes (T2D) are still limited. The study aimed at comparing effectiveness of 2BI (Gla-300 vs. iDeg-100) in insulin-naïve T2D. This was a retrospective, non-inferiority, multicenter study, from electronic medical records. All patients initiating Gla-300 or iDeg-100 in January 2017-2020 were 1:1 propensity score matched. Linear mixed models for repeated measures were applied to assess changes during 6 months in HbA1c, fasting blood glucose (FBG), body weight, and insulin doses. Incidence rates (IR) of hypoglycemic events were compared using Poisson regression models. Overall, 19 centers provided data on 357 patients in each PSM cohort. Estimated mean baseline levels of HbA1c were 9.2%. Marked reductions in HbA1c after 6 months were documented: -1.70%; (95%CI -1.90; -1.50) in Gla-300 group and -1.69%; (95%CI -1.89; -1.49) in IDeg-100 group (between group mean difference: 0.01; 95%CI -0.29; 0.27), confirming non-inferiority of Gla-300 vs. IDeg-100. FBG was reduced by about 60 mg/dl in both groups; minor changes in body weight were documented. In both groups, the mean prescribed dose was about 12 U (0.15 U/Kg) and was slightly titrated during 6 months up to +4U (0.20 U/Kg). IR (episodes per patient-months) of BG≤70 mg/dl was 0.13 (95%CI 0.07;0.26) in Gla-300 group and 0.14 (95%CI 0.07;0.27) in IDeg-100 group (p=0.87). IR of BG&amp;lt;54 mg/dL was 0.02 (95%CI 0.01;0.05) in Gla-300 group and 0.02 (95%CI 0.01;0.04) in IDeg-100 group (p=0.49). No severe hypoglycemic episodes were reported. In T2DM adults, initiation of Gla-300 or IDeg-100 was associated with similar improvements in glycemic control, no weight gain, low hypoglycemia rates, with no severe episodes. These data can contribute in overcoming clinical inertia in BI initiation and dose titration. Disclosure G. Fadini: Board Member; Self; Novo Nordisk, Sanofi, Speaker’s Bureau; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Lilly Diabetes, Novo Nordisk, Sanofi. R. Buzzetti: None. A. Nicolucci: Advisory Panel; Self; AstraZeneca, Research Support; Self; Novo Nordisk, Pikdare, Sanofi, Shionogi &amp; Co., Ltd., SOBI. M. Rossi: Research Support; Self; Novo Nordisk, Sanofi, Shionogi &amp; Co., Ltd., Swedish Orphan Biovitrum AB. M. Larosa: Employee; Self; Sanofi. D. Cucinotta: None. On behalf of restore-2 study group: n/a. Funding Sanofi

Glycemic Variability and Time in Range During Self-titration of Once Daily Insulin Glargine 300 U/ml Versus Neutral Protamine Hagedorn Insulin in Insulin-naïve Chinese Type 2 Diabetes Patients.

IntroductionTo compare glycemic variability (GV) and time in range (TIR) in Chinese patients with type 2 diabetes (T2D) initiated on once-daily bedtime insulin glargine 300U/ml (Gla-300) versus neutral protamine Hagedorn (NPH) insulin using continuous glucose monitoring (CGM).MethodsThis was a 24-week, open-label exploratory study with 1:1 randomization comparing patient-adjusted titration of Gla-300 (n = 23) versus NPH (n = 23) at bedtime in insulin-naïve T2D patients on maximum oral glucose-lowering drugs. The starting dose was 0.2 U/kg/day and with self-titration of one unit per week to achieve a target fasting glucose of 4.4–6 mmol/l, without hypoglycemia. Participants had masked CGM at baseline, weeks 11 and 24. The primary outcome was between-treatment differences in CGM glucose standard deviation (SD) at week 24.ResultsHbA1c at week 24 were similar, with 21% of Gla-300 versus 4% of NPH-treated patients achieving HbA1c < 7% without confirmed hypoglycemia. There were no differences in anytime glucose SD at week 24 (LS mean difference − 0.08 mmol/l, 95% CI [− 0.42–0.26], p = 0.63). Anytime %TIRs (3.9–10.0 mmol/l) at week 24 were similar (p = 0.91). Nocturnal % time below range < 3.9 mmol/l was significantly lower in the Gla-300 group (least squares (LS) mean difference – 5.03% [− 9.92 to − 0.14], p = 0.04) with lower % coefficient of variation (LS mean difference − 4.5% [− 8.1 to − 0.8], p = 0.018). Diurnal TIR was higher in Gla-300 patients at week 11 but there were no differences at week 24.ConclusionsOnce-daily bedtime Gla-300 was associated with lower nocturnal GV, time below range and self-reported hypoglycemia in insulin-naïve Chinese T2D patients over a 24-week study period, as compared with NPH insulin.Clinical Trial RegistrationClinicalTrials.gov Identifier: NCT03389490.Supplementary InformationThe online version contains supplementary material available at 10.1007/s13300-021-01046-6.

Comparative Effectiveness of Switching From First-Generation Basal Insulin to Glargine300U/ml or Degludec100U/ml in Type1 Diabetes: The RESTORE-1 Study.

IntroductionFollowing pivotal trials, real-world evidence is important to assess the impact of new drugs in everyday clinical practice. The RESTORE-1 study aimed to compare effectiveness and safety of the second-generation basal insulins (2BI), i.e., insulin glargine 300 U/ml (Gla-300) vs. degludec 100 U/ml (IDeg-100), in type 1 diabetes (T1D).MethodsRetrospective, non-inferiority, multicenter study, based on electronic medical records. All patients switching to Gla-300 or IDeg-100 from first-generation basal insulins (1BI) were 1:1 propensity score matched (PSM). Changes during 6 months in HbA1c (primary endpoint), fasting plasma glucose (FPG), body weight, and insulin doses were assessed using linear mixed models for repeated measures. Incidence rates (IR) of hypoglycemic events were assessed.ResultsOverall, 19 centers provided data on 585 patients in each PSM cohort. For both groups, statistically significant reductions in HbA1c from baseline to 6 months were documented: − 0.20%; (95% CI − 0.32; − 0.08) in the Gla-300 group and − 0.14%; (95% CI − 0.24; − 0.04) in the IDeg-100 group. The non-inferiority of Gla-300 vs. IDeg-100 was confirmed (non-inferiority margin of 0.30%; upper 95% CI at 6 months, 0.09%). No statistically significant between-group differences emerged in FPG and body weight. Dose changes of basal and short-acting insulin were small in both groups, but higher in the Gla-300 group than in the Deg-100 group (p < 0.006). Incidence rates (IR) of hypoglycemia (blood glucose ≤ 70 mg/dl and < 54 mg/dl) during the 6-month follow-up by treatment were slightly lower in the Gla-300 group than in the Deg-100 group [IR ratios 0.82 (95% CI 0.55; 1.22) and 0.83; (95% CI 0.38; 1.83), respectively]. Hypoglycemic events (blood glucose < 54 mg/dl) decreased at 6 months in both groups (p = 0.01 for Gla-300 and p < 0.001 for IDeg-100). There were no severe hypoglycemic events for Gla-300 and seven events for IDeg-100 (p = 0.02).ConclusionsSwitching from 1BI to 2BI in adults with T1D was associated with similar improvements in glycemic control and overall significant decrease in hypoglycemia, with no severe events with Gla-300. Effectiveness of both insulins was limited by under-titration.Supplementary InformationThe online version contains supplementary material available at 10.1007/s13300-020-00982-z.

Pharmacoeconomic comparison of insulin glargine and insulin detemir in diabetes mellitus type 2

Second generation insulin analogue — insulin glargine 300 UI/ml (GLA-300) — can provide an effective control of Diabetes Mellitus (DM) with minimal risk of hypoglycemic events and prevent of cardiovascular complications or events (CVS). Pharmacoeconomic comparison of most used insulins — GLA-300 and detemir (IDet) has been based on indirect treatment comparison in DM Type 2. Materials and methods. Indirect treatment comparison was created according to published data of a real world evidence data for the treatment of DM Type 2 with GLA-300 and IDet, and common comparator — GLA-100 — has been used. Patients (%) who reached HbA1c target were indicated as an efficacy criteria. Odds ratios (OR) were calculated for clinical efficacy and severe hypoglycemia’s rate comparisons for GLA-300 and IDet. Direct (cost of annual treatment, hypoglycemia correction, CVS treatment), indirect medical costs as well as indirect costs (GDP loses) were calculated for GLA-300 and IDet strategies. Sensitivity analysis has been performed for confirmation of the base scenario results. Results. GLA-300 has advantages vs IDet by efficacy and less risks of severe hypoglycemia (OR 1.27 CI 95 % 1.02; 1.58 and OR 0.72 CI 95 % 0.56; 0.88 accordingly). Probability of good control of DM Type 2 (based on target of HbA1c&lt;7.0 %) was higher on 27 % in GLA-300. Costs of insulins, expenditures for CVS treatment and payment for temporary disability were similar for GLA-300 and IDet groups (for the one-year treatment period), in the same time in GLA-300 group the less expenditures for hypoglycemia were observed. Total expenditures were slightly less for GLA-300 on 3.7 % vs IDet.Conclusion. GLA-300 and IDet have no economic advantages between groups in total costs, but GLA-300 has tended for economic benefi ts in compare with IDet in DM Type 2.

PDB11 - CHART REVIEW ANALYSIS OF INSULIN GLARGINE 300 AND INSULIN GLARGINE 100 USE IN FRANCE, SPAIN, AND GERMANY

In randomized controlled trials (RCTs) and real-world (RW) studies, adult patients (pts) with type 2 diabetes (T2D) treated with basal insulin (BI) analogues insulin glargine 300 U/ml (Gla-300) or insulin glargine 100 U/ml (Gla-100) had similar reductions in HbA1c and Gla-300 was associated with lower incidence of hypoglycaemia compared with Gla-100. This study evaluated clinical outcomes in pts with T2D who switched from any BI to Gla-300 or Gla-100 in France, Spain, and Germany. Interim data were obtained from medical records for 494 pts who switched to either Gla-300 (N=292) or Gla-100 (N=202). Differences in baseline (BL) characteristics and clinical outcomes between groups were evaluated, and physician reasons for selecting Gla-300 or Gla-100 were assessed. Patient demographics and comorbidities were generally similar between Gla-300 and Gla-100 groups: % female (39.4 vs 47.0%, respectively), mean BL HbA1c (8.4 vs 8.4%), Charlson Comorbidity Index score (0.78 vs 0.88). In the Gla-300 group, diabetic nephropathy (7.2 vs 2.5%; P=0.021), prior stroke/TIA (7.2 vs 2.5%; P=0.021), and BMI (mean 29.2 vs 28.4 kg/m2; P=0.024) was higher, and more pts reported any hypoglycaemic events prior to switch (37.0 vs 24.3%; P=0.012). At 6 months’ follow-up, reductions from BL in HbA1c (-1.07 vs -1.16%) and weight (-2.29 vs -2.09 kg) were similar. The unadjusted mean reduction in hypoglycaemic events/patient over 6 months was greater for Gla-300 (-1.29 vs -0.62; P=0.025). There were no meaningful differences in insulin dose change during the reported titration period (5.53 vs 6.00 U). This comparative EU study showed that at 6 months, changes in glycaemic control and weight from BL were similar; however, unadjusted reductions in hypoglycaemic events were greater for pts switching to Gla-300 than to Gla-100, as previously reported in RCTs and RW studies. Here, there was no difference in dose change 6 months after switching.

Basal-Bolus Insulin Therapy with Gla-300 During Hospitalization Reduces Nocturnal Hypoglycemia in Patients with Type 2 Diabetes Mellitus: A Randomized Controlled Study.

IntroductionAlthough reduction in the incidence of nocturnal hypoglycemia, as estimated by symptom or self-monitored plasma glucose, was shown to be more pronounced with 300 units/mL insulin glargine (Gla-300) than with 100 units/mL insulin glargine (Gla-100) in type 2 diabetes patients, the exact frequency of nocturnal hypoglycemia estimated with continuous glucose monitoring (CGM) has not been reported.MethodsForty patients with type 2 diabetes who were admitted for glycemic control with basal–bolus insulin therapy (BBT) were randomized into the Gla-100 and Gla-300 groups. Insulin doses were adjusted to maintain blood glucose levels within 100–120 mg/dL at each meal. Plasma glucose and C-peptide profiles were estimated serially after admission and before discharge. Daily CGM was also performed before discharge.ResultsIn the Gla-100 and Gla-300 groups, the mean duration of hospitalization was 15 ± 2 and 15 ± 1 days, respectively, and the mean basal insulin dose before discharge was 13 ± 7 and 15 ± 10 units, respectively. The dose of meal-time insulin was not different between the two groups. Compared with the Gla-300 group, the Gla-100 group had significantly lower nocturnal profiles of plasma glucose and C-peptide, but significantly higher frequency of CGM-estimated nocturnal hypoglycemia (10.7% ± 18.4% versus 1.2% ± 3.6%, P = 0.033).ConclusionIn type 2 diabetic patients, reduction in the incidence of CGM-estimated nocturnal hypoglycemia by BBT under tightly controlled diet therapy was higher with Gla-300 than with Gla-100.Trial RegistrationUMIN clinical trials registry (UMIN000023360).

Comparison of Insulin Glargine 300 Units/mL and 100 Units/mL in Adults With Type 1 Diabetes: Continuous Glucose Monitoring Profiles and Variability Using Morning or Evening Injections.

The objective of this study was to compare glucose control in participants with type 1 diabetes receiving insulin glargine 300 units/mL (Gla-300) or glargine 100 units/mL (Gla-100) in the morning or evening, in combination with mealtime insulin. In this 16-week, exploratory, open-label, parallel-group, two-period crossover study (clinicaltrials.gov identifier NCT01658579), 59 adults with type 1 diabetes were randomized (1:1:1:1) to once-daily Gla-300 or Gla-100 given in the morning or evening (with crossover in the injection schedule). The primary efficacy end point was the mean percentage of time in the target glucose range (80-140 mg/dL), as measured using continuous glucose monitoring (CGM), during the last 2 weeks of each 8-week period. Additional end points included other CGM glycemic control parameters, hypoglycemia (per self-monitored plasma glucose [SMPG]), and adverse events. The percentage of time within the target glucose range was comparable between the Gla-300 and Gla-100 groups. There was significantly less increase in CGM-based glucose during the last 4 h of the 24-h injection interval for Gla-300 compared with Gla-100 (least squares mean difference -14.7 mg/dL [95% CI -26.9 to -2.5]; P = 0.0192). Mean 24-h glucose curves for the Gla-300 group were smoother (lower glycemic excursions), irrespective of morning or evening injection. Four metrics of intrasubject interstitial glucose variability showed no difference between Gla-300 and Gla-100. Nocturnal confirmed (<54 mg/dL by SMPG) or severe hypoglycemia rate was lower for Gla-300 participants than for Gla-100 participants (4.0 vs. 9.0 events per participant-year; rate ratio 0.45 [95% CI 0.24-0.82]). Less increase in CGM-based glucose levels in the last 4 h of the 24-h injection interval, smoother average 24-h glucose profiles irrespective of injection time, and reduced nocturnal hypoglycemia were observed with Gla-300 versus Gla-100.

Glycaemic control and hypoglycaemia with new insulin glargine 300 U/ml versus insulin glargine 100 U/ml in people with type 2 diabetes using basal insulin and oral antihyperglycaemic drugs: the EDITION 2 randomized 12‐month trial including 6‐month extension

AimsTo compare the efficacy and safety of new insulin glargine 300 U/ml (Gla‐300) with insulin glargine 100 U/ml (Gla‐100) over 12 months of treatment in people with type 2 diabetes using basal insulin and oral antihyperglycaemic drugs (OADs).Methods EDITION 2 (NCT01499095) was a randomized, 6‐month, multicentre, open‐label, two‐arm, phase IIIa study investigating once‐daily Gla‐300 versus Gla‐100, plus OADs (excluding sulphonylureas), with a 6‐month safety extension.ResultsSimilar numbers of participants in each group completed 12 months of treatment [Gla‐300, 315 participants (78%); Gla‐100, 314 participants (77%)]. The reduction in glycated haemoglobin was maintained for 12 months with both treatments: least squares (LS) mean (standard error) change from baseline −0.55 (0.06)% for Gla‐300 and −0.50 (0.06)% for Gla‐100; LS mean difference −0.06 [95% confidence interval (CI) −0.22 to 0.10)%]. A significant relative reduction of 37% in the annualized rate of nocturnal confirmed [≤3.9 mmol/l (≤70 mg/dl)] or severe hypoglycaemia was observed with Gla‐300 compared with Gla‐100: rate ratio 0.63 [(95% CI 0.42–0.96); p = 0.031], and fewer participants experienced ≥1 event [relative risk 0.84 (95% CI 0.71–0.99)]. Severe hypoglycaemia was infrequent. Weight gain was significantly lower with Gla‐300 than Gla‐100 [LS mean difference −0.7 (95% CI −1.3 to −0.2) kg; p = 0.009]. Both treatments were well tolerated with a similar pattern of adverse events (incidence of 69 and 60% in the Gla‐300 and Gla‐100 groups).ConclusionsIn people with type 2 diabetes treated with Gla‐300 or Gla‐100, and non‐sulphonylurea OADs, glycaemic control was sustained over 12 months, with less nocturnal hypoglycaemia in the Gla‐300 group.