Real-World Effectiveness of the Gla-300 + Cap + App Program in Adult Users Living with Type 2 Diabetes in Taiwan.

INTRODUCTION: Health2Sync (H2S) is a digital health technology platform that provides coaching and titration support to patients with diabetes. The Mallya cap converts a conventional insulin pen into a smart connected device that can automatically synchronize dose values and associated timestamps (upon injection) to the H2S platform. This single-arm real-world study evaluated the effectiveness of insulin glargine 300 U/mL (Gla-300) combined with H2S and Mallya cap (Gla-300 + Cap + App program) on clinical outcomes among users with type 2 diabetes (T2D) in Taiwan. METHODS: Adults (aged ≥ 20 years) with T2D who were registered H2S users and initiated Mallya cap for a new/existing Gla-300 regimen (identification period May 1, 2021-May 31, 2022) were included in this retrospective cohort study. Follow-up data from H2S were collected for 90 days. Glycated hemoglobin (HbA1c) change (baseline to follow-up) and HbA1c goal attainment were primary outcomes. Hypoglycemia incidence and usage metrics of Mallya cap were secondary outcomes. RESULTS: Of 83 participants, 38.6% were new Gla-300 users. HbA1c was reduced in both new (- 2.4 [2.7] %, - 26.2 [29.5] mmol/mol) and previous Gla-300 users (- 0.5 [1.6] %, - 5.5 [17.5] mmol/mol). Reduction in HbA1c was significant (p < 0.05) in both groups. At follow-up, 43.4% of users had a reduction of > 0.5%. Mean HbA1c reductions increased numerically with higher baseline HbA1c and with longer duration of Mallya cap usage. CONCLUSIONS: Use of digital technology within a connected ecosystem such as Gla-300 + Cap + App program could help people with type 2 diabetes to improve their glycemic condition.

Real-World Study on Effectiveness of Insulin Glargine U300 After Oral Antidiabetic Drug Failure in Patients with Type 2 Diabetes in the Gulf Region.

INTRODUCTION: The effectiveness and safety of long-acting insulin glargine U300 (Gla-300), in patients with type 2 diabetes mellitus (T2DM) requiring insulin, has not been reported in the Gulf region. METHODS: Insulin-naïve patients with T2DM, uncontrolled on OADs, and prescribed Gla-300 were followed up in a 12-month prospective observational study. Gla-300 was titrated to glycemic targets. The primary endpoint (achieving glycemic targets) was evaluated at month 6 of treatment. The need for treatment intensification, safety, and patient-reported outcomes (PRO) were also reported. RESULTS: The study included 412 patients (61.7% men; age 52.2 ± 11.1 years and T2DM duration 10.7 ± 6.8 years). Almost 50% were on more than 3 OADs, mostly biguanides, sulfonylureas, and dipeptidyl-peptidase-4 inhibitors. Baseline HbA1c level was 9.2% ± 1.1% and targets were set at 6.9% ± 0.4%. Baseline fasting plasma glucose was 11.5 ± 3.8 mmol/l. Fifty-seven patients (13.8%) achieved glycemic targets at month 6, hindered by baseline HbA1c ≥ 10%, frequent co-morbidities, older age, suburban/rural residence, and full-time employment. Levels of HbA1c dropped progressively by 0.96% ± 0.07% (month 3), 1.29% ± 0.08% (month 6), and 1.76% ± 0.06% (month 12). Gla-300 dose was 17.0 ± 9.0 IU/day at baseline, 24.6 ± 9.6 IU/day at month 3, 28.5 ± 9.9 IU/day at month 6, and 30.7 ± 10.7 IU/day at month 12. Three patients experienced non-severe hypoglycemia and a slight decrease in body weight and PROs improved. CONCLUSIONS: In the Gulf, Gla-300 in patients with T2DM uncontrolled on OADs improved glycemic control, with low rates of hypoglycemia and improved PROs. Gla-300 dose up-titration from baseline to month 6 did not, however, result in a vast proportion of patients achieving their pre-determined HbA1c targets. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03703869.

Insulin Glargine in Type 1 Diabetes Mellitus: A Review of Clinical Trials and Real-world Evidence Across Two Decades.

BACKGROUND: Over the past two decades, insulin glargine 100 U/mL (Gla-100) has emerged as the "standard of care" basal insulin for the management of type 1 diabetes mellitus (T1DM). Both formulations, insulin glargine 100 U/mL (Gla-100) and glargine 300 U/mL (Gla- 300) have been extensively studied against various comparator basal insulins across various clinical and real-world studies. In this comprehensive article, we reviewed the evidence on both insulin glargine formulations in T1DM across clinical trials and real-world studies. METHODS: Evidence in T1DM for Gla-100 and Gla-300 since their approvals in 2000 and 2015, respectively, were reviewed. RESULTS: Gla-100 when compared to the second-generation basal insulins, Gla-300 and IDeg-100, demonstrated a comparable risk of overall hypoglycemia, but the risk of nocturnal hypoglycemia was higher with Gla-100. Additional benefits of Gla-300 over Gla-100 include a prolonged (>24- hours) duration of action, a more stable glucose-lowering profile, improved treatment satisfaction, and greater flexibility in the dose administration timing. CONCLUSION: Both glargine formulations are largely comparable to other basal insulins in terms of glucose-lowering properties in T1DM. Further, risk of hypoglycemia is lower with Gla-100 than Neutral Protamine Hagedorn but comparable to insulin detemir.

Use of Second-Generation Basal Insulin Gla-300 in Special Populations: A Narrative Mini-Review.

BACKGROUND AND AIMS: Hypoglycemia and insulin-related adverse events are crucial barriers to effective diabetes management, particularly in the elderly, people with renal impairment, people with diabetes fasting during Ramadan, or people with type 1 diabetes mellitus (T1DM). There is a scarcity of clinical and real-world evidence assessing the effectiveness and safety of insulin glargine 300 U/mL (Gla-300) in these special populations. To understand the entirety of evidence, this mini-review elaborates on the use of Gla-300 in diabetes management among special populations. METHODS: Clinical and real-world evidence related to the use of Gla-300 among special populations with diabetes were retrieved using PUBMED and Google Scholar. RESULTS: Gla-300 has shown improved glycemic control with stable insulin action and low risk of hypoglycemia in diverse groups with diabetes. It also appears to have an acceptable safety profile during Ramadan fasting. However, adequate monitoring and adjustment of insulin dose on an individual basis should be considered. CONCLUSION: Gla-300 is a second-generation basal insulin with proven benefits of reduced risk of hypoglycemia and improved glycemic control in special populations of people with diabetes.

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.

INTRODUCTION: Data 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. METHODS: This 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. RESULTS: One 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. CONCLUSION: This 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.

Effectiveness and safety of insulin glargine Gla-300 in insulin-naïve type 2 diabetes subjects in a real-life setting-the GOAL_RO trial.

BACKGROUND: Basal insulin is the first choice for insulin initiation in type 2 diabetes (T2DM), with the second generation of basal insulin analogues having a lower risk of hypoglycemia compared to the first generation of basal insulins. The aim of our study was to assess on a large cohort of insulin-naïve T2DM subjects the effectiveness and safety of insulin glargine 300 U/mL (Gla-300) in a real-life setting. METHODS: This was a multicenter, prospective, non-interventional, 24 weeks, 3 visits (baseline, 3 and 6 months) trial performed in adult T2DM subjects not achieving glycemic target (HbA1c >7%) with prior oral or GLP-1 RA therapy. The study included 1,095 subjects (55.2% M/44.8% F) in 124 study sites. Mean (±SD) age was 61.1±8.5 years while mean duration of diabetes was 8.8±5.2 years. Mean BMI was 31.7±5.4 kg/m2 with 91.2% being overweight or obese. Baseline diabetes treatment included metformin (88.4% of subjects), sulphonylureas (75.4%), DPP-4i (16.7%) and GLP-1 RAs (8%). Comparison between quantitative variables was made with the paired sample t test. RESULTS: Mean HbA1c at baseline was 9.8%±1.7% with a mean fasting plasma glucose (FBG) of 231.5±67.4 mg/dL. Mean HbA1c decreased to 7.7%±1.2% at 6 months with a mean change from baseline of -2.1% (P<0.001). Overall, 30.7% of subjects reached the HbA1c target of 7%. Final mean dose of Gla-300 was 0.4 IU/kg/day. Mean weight gain was 0.4 kg over 6 months. Adverse events (AEs) were reported by 11.1% of subjects with 2.3% reporting serious adverse events (SAEs). Overall, 4.4% of subjects reporting at least one event of symptomatic or confirmed hypoglycemia. Only 7 episodes of nocturnal and one of severe hypoglycemia were reported. CONCLUSIONS: In conclusion, a significant 2.1% decrease of HbA1c was recorded after 6 months of treatment with Gla-300 with no unexpected safety signals, low risk of hypoglycemia and modest weight gain.

Efficacy and Safety of Switching Patients Inadequately Controlled on Basal Insulin to Insulin Glargine 300 U/mL: The TRANSITION 2 Study.

INTRODUCTION: This study aimed to determine, in close to real-life conditions, the efficacy and safety of switching from any basal insulin to insulin glargine 300 U/mL (Gla-300) in patients with uncontrolled type 2 diabetes (T2D). METHODS: This was an interventional, multicenter, single-arm, prospective study with a 24-week treatment phase. Adult patients with T2D treated with basal insulin with or without other antidiabetics, HbA1c > 7.5%, and fasting self-monitored blood glucose (F-SMBG) > 130 mg/dL (mean of three measures) at baseline were included. Insulin dose was titrated to reach F-SMBG 90-130 mg/dL. Efficacy and safety were assessed at 12 weeks (W12) and 24 weeks (W24). The main outcome parameter was HbA1c change between baseline and W24. Safety parameters included self-reported hypoglycemia (any type). Patients' satisfaction with the treatment was assessed by the Diabetes Treatment Satisfaction Questionnaire (DTSQ). RESULTS: A total of 140 patients were included and 137 were treated. Mean HbA1c decreased from 8.64% at baseline to 8.14% at W12 (mean difference [95% CI] - 0.51% [- 0.64; - 0.38]) and 8.01% at W24 (- 0.64% [- 0.81; - 0.46]). Target F-SMBG was reached in 35.0% of the patients at W12 and 38.4% at W24. The percentages of patients reaching HbA1c levels < 7.0%, < 7.5%, and < 8.0% at W24 were 11.4%, 29.5%, and 50.8%, respectively, while only 31.6% had an HbA1c value < 8.0% at baseline. HbA1c reduction was greater in patients with higher baseline levels. During the treatment phase, 46.0% of the participants had at least one hypoglycemia event; 31.4% documented symptomatic hypoglycemia, 2.2% severe hypoglycemia, and 12.2% nocturnal hypoglycemia. Treatment satisfaction increased by 20% between baseline and W24. CONCLUSION: These data, derived from close to real-life practice in France, confirm the reassuring results of randomized trials on the efficacy and safety of Gla-300. TRIAL REGISTRATION: EudraCT number 2015-002416-33.

In Silico Examination of Initiation of Long-Acting Insulin Analogs Toujeo Compared to Lantus Under 3 Dosing Titration Rules in Virtual Type 2 Diabetes Subjects.

BACKGROUND: Despite the benefits and clinical necessity of insulin treatment in type 2 diabetes (T2D), healthcare providers are reluctant to initiate insulin, and patients are reluctant to start it for several reasons, one of these being the complexity of insulin treatment. Patients and their healthcare providers can benefit from titration algorithms (TAs) or rules that assist with the initiation and titration of insulin, performing the calculations that are needed to safely initiate and conservatively adjust. METHODS: The primary objective for this in silico study was to examine the effectiveness of 3 dose TAs (1-3) for optimization of basal insulin glargine (Gla-100 and Gla-300). In the simulations, 100 virtual subjects with T2D were included (50% men, age 62 ± 3 years, HbA1c 8.1% ± 2.9%, body weight 94 ± 16 kg). Subjects were studied under each TA (TA1 and TA2 fasting blood glucose [FBG] targets 90-130 mg/dL, TA3 FBG target 110-150 mg/dL). Initial dose of both insulins was based on 0.2 U/kg body weight. During 3 months, subjects reported their FBG to the LTHome web-based dose guidance system with a rules engine to safely guide long-acting insulin titration and maintenance. Subjects followed dose recommendations to reach designated FBG target ranges. RESULTS: All subjects reached stable doses under all TAs with both Gla-100 and Gla-300 insulin, and 93 or more of the 100 subjects, depending on the assigned TA, achieved the target FBG range within the 3-month simulation for all TAs. Mean FBG was lowered (Gla-100: 155 ± 40 to 118 ± 11 mg/dL with TA1 and TA2 and 132 ± 12 mg/dL for TA3; Gla-300: 125 ± 14 with TA1 and TA2 and 134 ± 15 mg/dL with TA3). Calculated HbA1c improved from 8.1% ± 2.9% to 7.1% ± 2.5% for TA1 and TA2 and 7.5% ± 2.5% for TA3, a reduction of 0.9% and 0.6% over 3 months for both insulins. Three subjects on Gla-100 and one subject on Gla-300 experienced mild hypoglycemia. CONCLUSION: All TAs delivered safe dose recommendations with minimal hypoglycemia, leading to a stable glucose control in the majority of subjects.

Hypoglycaemia and treatment patterns among insulin-treated patients with type 2 diabetes who switched to insulin glargine 300 units/mL versus other basal insulin in a real-world setting.

INTRODUCTION: Type 2 diabetes (T2D) is characterized by worsening pancreatic ß-cell function often requiring treatment escalation with oral antidiabetic drugs (OADs), glucagon-like peptide-1 and eventually insulin. Although there is much evidence available on the initiation of basal insulins, fewer studies have investigated the effects of switching from one basal insulin to another. This study aims to evaluate treatment persistence and hypoglycaemia in adult patients with T2D on prior basal insulin who were switched to insulin glargine 300 units/mL (Gla-300) or other basal insulins in a real-world setting. MATERIALS AND METHODS: This study is a retrospective cohort analysis of patient-level data extracted from the Optum® Clinformatics™ database between 1 October 2014 and 30 June 2016. Adult patients (≥18 years) with T2D who were being treated with basal insulin during the 6-month baseline period, who switched to either Gla-300 or other basal insulins, were followed up for ≥3 months after switching. Outcomes included treatment persistence, and incidence and number of hypoglycaemic events. RESULTS: Of the included patients, 1204 switched to Gla-300 and 616 switched to other basal insulins. Adjusting for baseline confounders, patients who switched to Gla-300 were 34% less likely to discontinue their basal insulin than patients who switched to other basal insulins (hazard ratio [HR] 0.66; 95% confidence interval [CI] 0.54-0.81; P < 0.001). Patients who switched to Gla-300 were less likely to experience hypoglycaemia at 3-month follow-up (odds ratio [OR] 0.56, 95% CI 0.32-0.97; P = 0.039) and at 6-month follow-up (OR 0.58, 95% CI 0.38-0.87; P = 0.009) compared with patients who switched to other basal insulins. CONCLUSIONS: Patients with T2D on prior basal insulin in a real-world setting who switched to Gla-300 were more persistent with their basal insulin and experienced less hypoglycaemia than patients who switched to other basal insulins.

American Diabetes Association - 76th Scientific Sessions (June 10-14, 2016 - New Orleans, Louisiana, USA).

The 76th American Diabetes Association (ADA) Scientific Sessions took place in New Orleans, Louisiana, USA. The meeting brought together scientists and professionals from a wide range of disciplines in the field of diabetes and provided a platform for networking, allowing experts and researchers to share ideas and learn about the significant advances in diabetes research, treatment and care. Over the course of the 5 days, participants received exclusive access to more than 2,500 original research presentations.

Accuracy and Injection Force of the Gla-300 Injection Device Compared With Other Commercialized Disposable Insulin Pens.

BACKGROUND: To deliver insulin glargine 300 U/mL (Gla-300), the widely used SoloSTAR(®) pen has been modified to allow for accurate and precise delivery of required insulin units in one-third of the volume compared with insulin glargine 100 U/mL, while improving usability. Here we compare the accuracy and injection force of 3 disposable insulin pens: Gla-300 SoloSTAR(®), FlexPen(®), and KwikPen™. METHODS: For the accuracy assessment, 60 of each of the 3 tested devices were used for the delivery of 3 different doses (1 U, half-maximal dose, and maximal dose), which were measured gravimetrically. For the injection force assessment, 20 pens of each of the 3 types were tested twice at half-maximal and once at maximal dose, at an injection speed of 6 U/s. RESULTS: All tested pens met the International Organization for Standardization (ISO) requirements for dosing accuracy, with Gla-300 SoloSTAR showing the lowest between-dose variation (greatest reproducibility) at all dose levels. Mean injection force was significantly lower for Gla-300 SoloSTAR than for the other 2 pens at both half maximal and maximal doses (P < .0271). CONCLUSION: All tested pens were accurate according to ISO criteria, and the Gla-300 SoloSTAR pen displayed the greatest reproducibility and lowest injection force of any of the 3 tested devices.

A review of the safety and efficacy data for insulin glargine 300 units/ml, a new formulation of insulin glargine.

Insulin glargine 100 units/ml (Gla-100) has become a standard of care in diabetes treatment over the past decade, providing 24-h basal insulin coverage after once-daily subcutaneous injection for many people with diabetes, with a well-established efficacy and safety profile. New insulin glargine 300 units/ml (Gla-300) is a basal insulin that provides the same number of units as Gla-100 in a third of the volume. Compared with Gla-100, Gla-300 has shown more constant and prolonged pharmacokinetic (PK)/pharmacodynamic (PD) profiles. This review summarizes the findings from the EDITION series of clinical trials that investigated Gla-300 in individuals with type 1 and type 2 diabetes mellitus. Overall, Gla-300 has been shown to achieve similar glycaemic control with less, or similar, nocturnal hypoglycaemia compared with Gla-100, and a trend towards lower hypoglycaemia at any time of day. The EDITION series of clinical trials also provides some evidence for less weight gain with Gla-300 than with Gla-100. In addition, the PK/PD profiles of Gla-300 may allow more flexibility in the timing of doses, improving convenience; thus, Gla-300 could offer several positive features for individuals with diabetes requiring basal insulin therapy.

U300 Insulin Glargine: A Novel Basal Insulin for Type 1 and Type 2 Diabetes.

Objective: To review clinical efficacy and safety of insulin glargine 300 units/mL (Gla-300), a novel high-concentration basal insulin. Data Sources: A MEDLINE search was performed to identify relevant articles published 1960 through February 2015 using the search term glargine 300. Published abstracts from conference proceedings of the American Diabetes Association 74th Scientific Sessions were identified. Study Selection and Data Extraction: Human studies that evaluated pharmacokinetics, efficacy, or safety of Gla-300 were included. Data Synthesis: Six trials investigated efficacy and safety of Gla-300; 3 of 6 trials were available in abstract form only. The EDITION group of trials compared Gla-300 to insulin glargine 100 units/mL (Gla-100) in several populations. These included subjects with type 1 diabetes continuing mealtime insulin and subjects with type 2 diabetes on basal and mealtime insulin, basal insulin and oral antidiabetic drugs (OADs), and with no prior insulin use. Three studies were multinational including 2 studies exclusive to Japanese participants. Each clinical trial was an open-label, multicenter, randomized study with 6 to 12 months of follow-up. Gla-300 demonstrated similar reductions in HbA1c compared to Gla-100. Basal insulin requirements increased by 11% to 17% with Gla-300 without excessive weight gain. Rates of overall hypoglycemia were similar with Gla-300 compared to Gla-100; however, 16% to 38% less nocturnal hypoglycemia was observed in type 2 clinical trials. Conclusions: Gla-300 in combination with mealtime insulin or OADs has shown comparable glycemic control with higher insulin dose requirements versus Gla-100, and may induce less hypoglycemia in patients with type 2 diabetes.