Effectiveness and safety of insulin glargine 300 U/mL in insulin-naïve individuals according to diabetes duration: Results from the REALI European pooled data analysis.

AIM: To evaluate the effectiveness and safety of insulin glargine 300 U/mL (Gla-300) initiation according to diabetes duration (DD). MATERIALS AND METHODS: We analysed patient-level data from 2381 insulin-naïve individuals with type 2 diabetes (T2D), of whom 2349 (98.7%) were treated with Gla-300 for 24 weeks. Of the 2381 participants, 1048 (44.0%) had a DD of less than 8 years and 1333 (56.0%) had a DD of 8 years or longer. We further analysed the subgroups of participants having a DD of less than 4 years (N = 450), 4-8 years (N = 598), 8-12 years (N = 627) and 12 years or longer (N = 706). RESULTS: Mean ± standard deviation age was 60.2 ± 9.0 years in participants with a DD less than 8 years and 64.2 ± 8.8 years in those with a DD of 8 years or longer. At 24 weeks of Gla-300 therapy, HbA1c improved with a least-squares (LS) mean change from baseline of -1.88% (95% confidence interval [CI], -1.95 to -1.80) and -1.71% (95% CI, -1.77 to -1.65), respectively, resulting in a LS mean difference between groups of 0.17% (95% CI, 0.07 to 0.26; P = .0005). In the subgroup analysis, LS mean HbA1c reduction from baseline to week 24 was highest in participants with a DD of less than 4 years and lowest in participants with a DD of 12 years or longer. Overall, incidences of symptomatic and severe hypoglycaemia were low, irrespective of DD, without body weight changes. CONCLUSIONS: Gla-300 was effective and safe in insulin-naïve individuals with T2D, regardless of DD. Improvement in HbA1c was greater when Gla-300 was initiated in participants with a DD of less than 4 years, although the difference between the groups was modest.

Italian Titration Approach Study (ITAS) with insulin glargine 300 U/mL in insulin-naïve type 2 diabetes: Design and population.

BACKGROUND AND AIMS: Fostering patient's self-managing of basal insulin therapy could improve glucose control, by removing patient's and physician's barriers to basal insulin initiation, titration and glucose monitoring. The Italian Titration Approaches Study (ITAS) aims at demonstrating non-inferiority (<0.3% margin) in efficacy of glucose control (change in glycated hemoglobin [HbA1c] after 24 weeks) by the same titration algorithm of insulin glargine 300 U/mL (Gla-300), managed by the (nurse assisted) patient versus the physician, in insulin naïve patients with Type 2 Diabetes Mellitus (T2DM), uncontrolled with previous treatments. METHODS AND RESULTS: ITAS is a phase IV, 24-week, national, multicenter, open label, randomized (1:1) parallel group study. 458 patients were enrolled, 359 randomized, and 339 completed the study, in 46 Italian centers. Baseline characteristics and previous medications of the ITT population (N = 355) are reported. Mean ± SD age, T2DM duration, HbA1c, FPG and BMI were 64.0 ± 9.8 years, 11.6 ± 7.6 years, 8.79 ± 0.65%, 170.9 ± 42.3 mg/dL, and 30.3 ± 5.6 kg/m2, respectively. Vascular and metabolic disorders were most frequent (73.8% and 58.3%, respectively). More than 90% of patients were on metformin. CONCLUSION: ITAS is the first study to compare two different managers (nurse-assisted patient vs physician) of the same titration algorithm of Gla-300 in insulin naïve patients with T2DM in unsatisfactory glucose control. This study might provide novel evidence on the efficacy/effectiveness of patient-managed titration algorithm of Gla-300 in a pragmatic setting and may reduce barriers to basal insulin initiation and its titration.

Comparison of tofogliflozin 20 mg and ipragliflozin 50 mg used together with insulin glargine 300 U/mL using continuous glucose monitoring (CGM): A randomized crossover study.

To investigate whether sodium glucose co-transporter 2 inhibitors (SGLT2i), tofogliflozin or ipragliflozin, achieve optimal glycemic variability, when used together with insulin glargine 300 U/mL (Glargine 300). Thirty patients with type 2 diabetes were randomly allocated to 2 groups. For the first group: After admission, tofogliflozin 20 mg was administered; Fasting plasma glucose (FPG) levels were titrated using an algorithm and stabilized at 80 mg/dL level with Glargine 300 for 5 days; Next, glucose levels were continuously monitored for 2 days using continuous glucose monitoring (CGM); Tofogliflozin was then washed out over 5 days; Subsequently, ipragliflozin 50 mg was administered; FPG levels were titrated using the same algorithm and stabilized at 80 mg/dL level with Glargine 300 for 5 days; Next, glucose levels were continuously monitored for 2 days using CGM. For the second group, ipragliflozin was administered prior to tofogliflozin, and the same regimen was maintained. Glargine 300 and SGLT2i were administered at 8:00 AM. Data collected on the second day of measurement (mean amplitude of glycemic excursion [MAGE], average daily risk range [ADRR]; on all days of measurement) were analyzed. Area over the glucose curve (<70 mg/dL; 0:00 to 6:00, 24-h), M value, standard deviation, MAGE, ADRR, and mean glucose levels (24-h, 8:00 to 24:00) were significantly lower in patients on tofogliflozin than in those on ipragliflozin. Tofogliflozin, which reduces glycemic variability by preventing nocturnal hypoglycemia and decreasing postprandial glucose levels, is an ideal SGLT2i when used together with Glargine 300 during basal insulin therapy.

Glycaemic Control in People with Type 2 Diabetes Mellitus Switching from Basal Insulin to Insulin Glargine 300 U/ml (Gla-300): Results from the REALI Pooled Database.

INTRODUCTION: Using pooled data from the REALI European database, we evaluated the impact of previous basal insulin (BI) type on real-life effectiveness and safety of switching to insulin glargine 300 U/ml (Gla-300) in people with suboptimally controlled type 2 diabetes. METHODS: Patient-level data were pooled from 11 prospective, open-label, 24-week studies. Participants were classified according to the type of prior BI. Of the 4463 participants, 1282 (28.7%) were pre-treated with neutral protamine Hagedorn (NPH) insulin and 2899 (65.0%) with BI analogues (BIAs), and 282 (6.3%) had undetermined prior BI. RESULTS: There were no meaningful differences in baseline characteristics between subgroups, except for a higher prevalence of diabetic neuropathy in the NPH subgroup (21.6% versus 7.8% with BIAs). Mean ± standard deviation haemoglobin A1c (HbA1c) decreased from 8.73 ± 1.15% and 8.35 ± 0.95% at baseline to 7.71 ± 1.09% and 7.82 ± 1.06% at week 24 in the NPH and BIA subgroups, respectively. Least squares (LS) mean change in HbA1c was - 0.85% (95% confidence interval - 0.94 to - 0.77) in NPH subgroup and - 0.70% (- 0.77 to - 0.64) in BIA subgroup, with a LS mean absolute difference between subgroups of 0.16 (0.06-0.26; p = 0.002). Gla-300 mean daily dose was slightly increased at week 24 by 0.07 U/kg/day (approximately 6 U/day) in both subgroups. Incidences of symptomatic and severe hypoglycaemia were low, without body weight change. CONCLUSIONS: Irrespective of previous BI therapy (NPH insulin or BIAs), switching to Gla-300 improved glycaemic control without weight gain and with low symptomatic and severe hypoglycaemia incidences. However, a slightly greater glucose-lowering effectiveness was observed in people pre-treated with NPH insulin.

Does Gender Influence the Effectiveness and Safety of Insulin Glargine 300 U/ml in Patients with Uncontrolled Type 2 Diabetes? Results from the REALI European Pooled Analysis.

INTRODUCTION: Gender differences in risk factors and treatment outcomes for type 2 diabetes mellitus (T2DM) may exist. We used the REALI European database to investigate whether there were gender-specific differences in baseline characteristics and clinical outcomes among patients with inadequately controlled T2DM initiated on insulin glargine 300 U/ml (Gla-300). METHODS: Data were pooled from 14 multicentre, prospective, interventional and non-interventional studies. Impact of gender on glycaemic control, insulin dose, body weight and hypoglycaemia was evaluated after 12 and 24 weeks of Gla-300 treatment. RESULTS: Women (N = 3857) were older than men (N = 4376) (median age, 65.0 versus 63.0 years), with greater mean body mass index (32.5 versus 31.6 kg/m2) and lower median estimated glomerular filtration rate (77.5 versus 84.0 ml/min/1.73 m2). Peripheral arterial disease and a history of myocardial infarction were more frequent in men (20.1% versus 11.7% and 12.0% versus 5.8%, respectively). At baseline, mean haemoglobin A1c (HbA1c) was 8.74% in men and 8.79% in women. Least square (LS) mean (95% CI) reduction in HbA1c from baseline to week 24 was - 1.17% (- 1.21 to - 1.13) in men and - 1.07% (- 1.11 to - 1.02) in women, resulting in a LS mean difference of - 0.10% (- 0.15 to - 0.05; p < 0.0001). At 24 weeks, 21.6% of women and 27.2% of men achieved target HbA1c of < 7.0% (p < 0.001; chi-square). Reported incidence for symptomatic (8.5% versus 8.7%) and severe (0.3% versus 0.5%) any-time-of-the-day or symptomatic (2.4% versus 1.8%) and severe (0.1% versus 0.2%) nocturnal hypoglycaemia was overall low and comparable between men and women. Changes in daily Gla-300 dose and body weight were also similar. CONCLUSION: Despite some gender differences in baseline characteristics, Gla-300 treatment improved glycaemic control, with overall low hypoglycaemia incidences in both men and women. However, women had statistically significantly lower HbA1c reductions than men, although these differences were clinically modest.

Efficacy and Safety of Insulin Glargine 300 U/mL in People with Type 2 Diabetes Uncontrolled on Basal Insulin: The 26-Week Interventional, Single-Arm ARTEMIS-DM Study.

INTRODUCTION: The efficacy and safety of switching to insulin glargine 300 U/mL (Gla-300) in type 2 diabetes mellitus (T2DM) uncontrolled on basal insulin (BI) has been demonstrated in the North American and Western European populations; however, there is limited data from other geographical regions with different ethnicities. The ARTEMIS-DM study aimed to evaluate the efficacy and safety of Gla-300 in people with T2DM uncontrolled on BI from Asia, Latin America and Middle East Africa. METHODS: The ARTEMIS-DM was a 26-week, prospective, interventional, single-arm, phase IV study (NCT03760991). Adults with T2DM previously uncontrolled (glycated haemoglobin [HbA1c] 7.5-10%) on BI were switched to Gla-300. The primary endpoint was change in HbA1c from baseline to 26 weeks. Key secondary endpoints were changes in HbA1c (week 12), fasting plasma glucose (FPG), self-monitored plasma glucose (SMPG) and BI dose from baseline to week 26. The safety and tolerability of Gla-300 were also assessed. RESULTS: A total of 372 (50% male) participants were included, with mean (standard deviation [SD]) age 60.9 (10.0) years, duration of diabetes 13.11 (7.48) years and baseline HbA1c 8.67 (0.77)% (71.22 [8.44] mmol/mol). A total of 222 (59.7%) participants were using insulin glargine 100 U/mL and 107 (28.8%) were using neutral protamine Hagedorn insulin as previous BI. There were clinically significant reductions in mean HbA1c (- 0.82%; primary endpoint), FPG and SMPG levels at week 26. With a pre-defined titration algorithm, mean Gla-300 dose increased from 27.48 U (0.35 U/kg) at baseline to 39.01 U (0.50 U/kg) at week 26. Hypoglycaemia events occurred in 20.4% of the participants; 1 (0.3%) participant had a severe hypoglycaemia event. CONCLUSION: In people with T2DM uncontrolled on previous BI, switching to Gla-300 with optimal titration guided by an algorithm was associated with improved glycaemic control and low incidence of hypoglycaemia across multiple geographic regions. GOV IDENTIFIER: NCT03760991.

Clinical Use of Insulin Glargine 300 U/mL in Adults with Type 2 Diabetes: Hypothetical Case Studies.

Type 2 diabetes (T2D) is a progressive disease, with many individuals eventually requiring basal insulin therapy to maintain glycaemic control. However, there exists considerable therapeutic inertia to the prompt initiation and optimal titration of basal insulin therapy due to barriers that include fear of injections, hypoglycaemia, weight gain, and burdensome regimens. Hypoglycaemia is thought to be a major barrier to optimal glycaemic control and is associated with significant morbidity and mortality. Newer second-generation basal insulin analogues provide comparable glycaemic control with lower risk of hypoglycaemia compared with first-generation basal insulin analogues. The present review article discusses clinical evidence for one such second-generation basal insulin analogue, insulin glargine 300 U/mL (Gla-300), in the context of hypothetical case studies that are representative of individuals who may attend routine clinical practice. These case studies discuss individualised treatment needs for people with T2D who are insulin-naïve or pre-treated. Clinical characteristics such as older age, frequent nocturnal hypoglycaemia, and renal impairment, which are known risk factors for hypoglycaemia, are also considered.

Safety and Effectiveness of Insulin Glargine 300 U/mL in Participants with Type 2 Diabetes Who Fast During Ramadan in The Gulf Region: A Subgroup Analysis of the Real-World ORION Study.

INTRODUCTION: To evaluate the safety and effectiveness of insulin glargine 300 U/mL (Gla-300) in people with type 2 diabetes mellitus (T2DM) in the Gulf region who fast during Ramadan. METHODS: ORION was a real-world, prospective, observational study in people with T2DM treated with Gla-300 during pre-Ramadan, Ramadan, and post-Ramadan periods. This subgroup analysis included 222 participants from the Gulf region (Kuwait, Saudi Arabia, United Arab Emirates, and Qatar). The primary endpoint was the percentage of participants experiencing severe and/or symptomatic documented hypoglycemia (self-monitored plasma glucose [SMPG] ≤ 70 mg/dL) during Ramadan. Changes in glycated hemoglobin (HbA1c), fasting plasma glucose (FPG), SMPG, body weight, insulin dose, and adverse events (AEs) were also evaluated. RESULTS: The primary endpoint was reported in one (0.5%) participant during Ramadan. The incidence rate of symptomatic documented hypoglycemia (SMPG ≤ 70 mg/dL) decreased from the pre-Ramadan (3.2%) to Ramadan period (0.5%), and no severe hypoglycemia events were reported during the study. Reductions were observed in HbA1c (mean ± standard deviation: - 0.51 ± 0.95% [- 5.5 ± 10.4 mmol/mol]), FPG (- 13.9 ± 47.5 mg/dL), and SMPG (- 6.1 ± 27.1 mg/dL). No significant changes were observed in body weight or Gla-300 dose. AEs were reported in 11 (5.0%) participants. CONCLUSION: In a real-world setting in the Gulf region, Gla-300 treatment in people with T2DM during Ramadan was associated with a low incidence of hypoglycemia and improved glycemic control. TRIAL REGISTRATION: CTRI/2019/02/017636.

A Real-World Observational Study of Gla-300 in Adults with Type 2 Diabetes Who Fast During Ramadan in the South Asia Region: A Subgroup Analysis of the ORION Study.

INTRODUCTION: In this ORION study subgroup analysis, the safety and effectiveness of insulin glargine 300 U/mL (Gla-300) was evaluated in people from the South Asia region with type 2 diabetes mellitus (T2DM) before, during, and after Ramadan, in a real-world setting. METHODS: The ORION study was a real-world, prospective, observational, non-comparative study conducted across 11 countries. The current subgroup analysis included participants from the South Asia region (India and Pakistan) who fasted during Ramadan. The primary endpoint was the percentage of participants experiencing ≥ 1 event of severe and/or symptomatic documented hypoglycemia with self-monitored plasma glucose (SMPG) ≤ 70 mg/dL during Ramadan. Secondary endpoints analyzed were changes in glycated hemoglobin (HbA1c), fasting plasma glucose (FPG), SMPG, insulin dose, and adverse events (AEs). RESULTS: This subgroup analysis included 106 participants from the South Asia region with mean (standard deviation) age of 51.3 (10.9) years and mean number of 29.8 (4.0) fasting days. The number of severe and/or symptomatic documented hypoglycemia events was low in the pre-Ramadan (SMPG ≤ 70 mg/dL: 1 event [0.9%]; SMPG < 54 mg/dL: 1 event [0.9%]) and Ramadan periods (SMPG ≤ 70 mg/dL: 1 event [0.9%]; SMPG < 54 mg/dL: 0 events), and none in the post-Ramadan period. One participant reported severe hypoglycemia (any time of the day: nocturnal or daytime) throughout the pre-Ramadan period. A reduction in HbA1c and FPG levels was seen during the pre- to post-Ramadan period; however, a slight increase in SMPG levels was reported during this same period. Gla-300 daily dose was reduced from 21.6 (9.6) U to 20.2 (8.9) U during the pre-Ramadan to Ramadan period. The incidence of AEs was 1.9%. CONCLUSIONS: The real-world data from the ORION study indicate that Gla-300 is effective, with low risk of hypoglycemia, for the management of T2DM during Ramadan in the South Asian population. TRIAL REGISTRATION: CTRI/2019/02/017636.

Real-World Effectiveness and Safety of Insulin Glargine 300 U/mL in Insulin-Naïve People with Type 2 Diabetes: the ATOS Study.

INTRODUCTION: The clinical benefits of insulin glargine 300 U/mL (Gla-300) have been confirmed in randomised clinical trials (EDITION programme and BRIGHT) and real-world studies in the USA and Western Europe. ATOS evaluated the real-world effectiveness and safety of Gla-300 in wider geographic regions (Asia, the Middle East, North Africa, Latin America and Eastern Europe). METHODS: This prospective observational, international study enrolled adults (≥ 18 years) with type 2 diabetes mellitus (T2DM) uncontrolled [haemoglobin A1c (HbA1c) > 7% to ≤ 11%] on one or more oral anti-hyperglycaemic drugs (OADs) who had been advised by their treating physician to add Gla-300 to their existing treatment. The primary endpoint was achievement of a pre-defined individualised HbA1c target at month 6. RESULTS: Of the 4550 participants included, 4422 (51.8% female) were eligible for assessment. The mean ± standard deviation (SD) age was 57.2 ± 10.8 years, duration of diabetes was 10.2 ± 6.2 years and baseline HbA1c was 9.28 ± 1.0%. The proportion of participants reaching their individualised glycaemic target was 25.2% [95% confidence interval (CI) 23.8-26.6%] at month 6 and 44.5% (95% CI 42.9-46.1%) at month 12. At months 6 and 12, reductions were observed in HbA1c (-1.50% and -1.87%) and fasting plasma glucose (-3.42 and -3.94 mmol/L). Hypoglycaemia incidence was low, and body weight change was minimal. Adverse events were reported in 283 (6.4%) participants, with 57 (1.3%) experiencing serious adverse events. CONCLUSION: In a real-world setting, initiation of Gla-300 in people with T2DM uncontrolled on OADs resulted in improved glycaemic control and low rates of hypoglycaemia with minimal weight change. TRIAL REGISTRATION: Clinicaltrials.gov number NCT03703869.

Similar glycaemic control and risk of hypoglycaemia with patient- versus physician-managed titration of insulin glargine 300 U/mL across subgroups of patients with T2DM: a post hoc analysis of ITAS.

AIMS: The Italian Titration Approach Study (ITAS) demonstrated comparable HbA1c reductions and similarly low hypoglycaemia risk at 6 months in poorly controlled, insulin-naïve adults with T2DM who initiated self- or physician-titrated insulin glargine 300 U/mL (Gla-300) in the absence of sulphonylurea/glinide. The association of patient characteristics with glycaemic and hypoglycaemic outcomes was assessed. METHODS: This post hoc analysis investigated whether baseline patient characteristics and previous antihyperglycaemic drugs were associated with HbA1c change and hypoglycaemia risk in patient- versus physician-managed Gla-300 titration. RESULTS: HbA1c change, incidence of hypoglycaemia (any type) and nocturnal rates were comparable between patient- and physician-managed arms in all subgroups. Hypoglycaemia rates across subgroups (0.03 to 3.52 events per patient-year) were generally as low as observed in the full ITAS population. Small increases in rates of 00:00-pre-breakfast and anytime hypoglycaemia were observed in the ≤ 10-year diabetes duration subgroup in the patient- versus physician-managed arm (heterogeneity of effect; p < 0.05). CONCLUSIONS: Comparably fair glycaemic control and similarly low hypoglycaemia risk were achieved in almost all patient subgroups with patient- versus physician-led Gla-300 titration. These results reinforce efficacy and safety of Gla-300 self-titration across a range of phenotypes of insulin-naïve people with T2DM. CLINICAL TRIAL REGISTRATION: EudraCT 2015-001167-39.

Comparative clinical outcomes of insulin degludec and insulin glargine 300 U/mL after switching from other basal insulins in real-world patients with type 1 and type 2 diabetes.

AIMS/INTRODUCTION: To evaluate and compare the efficacy of insulin degludec (IDeg) and insulin glargine 300 U/mL (Gla300) 6 months after switching from other basal insulins by assessing the changes in glycated hemoglobin (HbA1c), body mass index (BMI), and insulin doses in patients with type 1 and type 2 diabetes in a real-world clinical setting. MATERIALS AND METHODS: A total of 307 patients with type 1 diabetes and 294 patients with type 2 diabetes with HbA1c >7.0% were studied. Adjusted mean changes in HbA1c, BMI, and insulin doses were compared between IDeg (IDeg group) and Gla300 (Gla300 group) switchers. Multivariable logistic regression analyses were carried out to examine whether the IDeg or Gla300 group was associated with HbA1c or insulin dose reduction and BMI gain. RESULTS: HbA1c was significantly decreased in both the IDeg and Gla300 groups. Adjusted mean changes in HbA1c (approximately -0.3% and -0.5% in type 1 diabetes and type 2 diabetes patients, respectively) and BMI were similar between both groups. The mean change in insulin dose was slightly larger for dose reduction in the IDeg group than in the Gla300 group. Multivariable logistic regression models showed that the IDeg group was significantly associated with insulin dose reduction after adjusting for basal insulin type, insulin dose, and number of basal insulin injections at baseline and other confounding factors. CONCLUSIONS: The current study suggested that IDeg and Gla300 have similar effects in reducing HbA1c and gaining BMI after switching from other basal insulins in Japanese patients with type 1 diabetes and type 2 diabetes. IDeg selection was associated with insulin dose reduction.

Glycaemic Control with Insulin Glargine 300 U/mL in Individuals with Type 2 Diabetes and Chronic Kidney Disease: A REALI European Pooled Data Analysis.

INTRODUCTION: Management of type 2 diabetes mellitus (T2DM) in patients with chronic kidney disease is complex. Using the REALI European pooled database, we determined the impact of baseline renal function on the effectiveness and safety of insulin glargine 300 U/mL (Gla-300) initiated in adults with inadequately controlled T2DM. METHODS: Data from 1712 patients with available estimated glomerular filtration rate (eGFR) at baseline were pooled from six 24-week prospective studies. Patients who received once-daily subcutaneous injections of Gla-300 were classified into four renal function subgroups, according to baseline eGFR: ≥ 90 (N = 599), 60-89 (N = 786), 45-59 (N = 219), and 15-44 mL/min/1.73 m2 (N = 108). RESULTS: Compared to those with baseline eGFR ≥ 60 mL/min/1.73 m2, patients with lower eGFR values tended to be older, had a longer T2DM duration, and were more likely to present diabetic complications. After 24 weeks of Gla-300 therapy, the least-squares mean (95% confidence interval) decrease in haemoglobin A1c (HbA1c) from baseline (- 1.14% [- 1.28 to - 1.00], - 1.21% [- 1.34 to - 1.08], - 1.19% [- 1.36 to - 1.01], and - 0.99% [- 1.22 to - 0.76]) and the proportion of patients achieving HbA1c < 7.5% (53.3%, 51.3%, 49.5%, and 51.5%) were comparable in the ≥ 90, 60-89, 45-59, and 15-44 mL/min/1.73 m2 subgroups, respectively. Although the incidence of hypoglycaemia was overall low, more patients in the eGFR 15-44 mL/min/1.73 m2 subgroup experienced hypoglycaemia at night or at any time of the day compared with higher eGFR subgroups. There were no notable differences between the renal function subgroups in the changes in Gla-300 daily dose and body weight from baseline to week 24. CONCLUSION: Although an eGFR of 15-44 mL/min/1.73 m2 was associated with a slightly increased risk of hypoglycaemia among patients with inadequately controlled T2DM, Gla-300 provided glycaemic improvement with an overall favourable safety profile regardless of baseline eGFR.

Impact of Age on the Effectiveness and Safety of Insulin Glargine 300 U/mL: Results from the REALI European Pooled Data Analysis.

INTRODUCTION: Patients aged ≥ 65 years continue to be underrepresented in clinical studies related to type 2 diabetes mellitus (T2DM). Accordingly, the REALI pooled analysis was performed to evaluate the effectiveness and safety of insulin glargine 300 U/mL (Gla-300) across different age subgroups, using data from 14 interventional and non-interventional studies. METHODS: Pooled efficacy and safety data were collected from 8106 European patients with uncontrolled T2DM who were initiated on or switched to Gla-300 injected once daily for 24 weeks. Patients were categorised into five age subgroups: < 50 (N = 727), 50-59 (N = 2030), 60-69 (N = 3054), 70-79 (N = 1847) and ≥ 80 years (N = 448). RESULTS: Mean baseline haemoglobin A1c (HbA1c) decreased linearly from the youngest (9.10%) to the oldest (8.46%) age subgroup. Following Gla-300 initiation, there were similar HbA1c reductions across age groups, with a least squares mean (95% confidence interval) change in HbA1c from baseline to week 24 of - 1.09% (- 1.18 to - 1.00), - 1.08% (- 1.14 to - 1.03), - 1.12% (- 1.17 to - 1.07), - 1.18% (- 1.24 to - 1.12) and - 1.11% (- 1.23 to - 0.99) in the < 50, 50-59, 60-69, 70-79 and ≥ 80 years subgroups, respectively. The incidences and event rates of reported hypoglycaemia were overall low. Compared to younger age subgroups, lower incidences of symptomatic hypoglycaemia occurring at any time of the day (5.9 vs. 7.6-9.4% for the younger subgroups) or during the night (0.5 vs. 1.6-2.5%) were recorded in patients aged ≥ 80 years. By contrast, the highest incidence of severe hypoglycaemia occurring any time of the day was reported in the subgroup aged ≥ 80 years (1.1 vs. 0.1-0.6% for the younger age subgroups). CONCLUSION: Gla-300 initiated in patients with uncontrolled T2DM provides glycaemic improvement with a favourable safety profile across a wide range of ages.

Real-World Effectiveness and Safety of Insulin Glargine 300 U/mL in Patients with T2D Uncontrolled on NPH or Premixed Insulins as Part of Routine Clinical Practice in Bulgaria: ToUPGRADE Study.

INTRODUCTION: The aim of this study is to demonstrate the real-life effectiveness and safety of insulin glargine 300 U/mL (Gla-300) in patients with type 2 diabetes (T2D) previously uncontrolled on NPH ± prandial insulin or premixed insulins in routine clinical practice in Bulgaria. METHODS: This was a 24-week prospective, observational study performed in 40 inpatient and outpatient sites across the country. RESULTS: A total of 286 patients were included in the study. The mean age (± SD) was 61.2 ± 10.0 years with duration of diabetes of 11.64 ± 7.5 years and body mass index (BMI) of 32.1 ± 5.7 kg/m2. HbA1c before Gla-300 initiation was 9.8 ± 1.0%, and fasting plasma glucose (FPG) was 13.1 ± 3.4 mmol/L. HbA1c and FPG change from baseline to week 24 was - 1.86% (p < 0.001) and - 4.8 mmol/L (p < 0.001), respectively. The proportion of patients reaching their individualized HbA1c at week 24 was 39.1% (95% CI 33.3-45.1%), while the proportion of patients reaching their individualized HbA1c target without confirmed and/or severe hypoglycaemia was 34.8% (95% CI 29.2-40.7%). At study end, 19.0% (95% CI 14.6-24.1%) achieved HbA1c < 7%. Body weight decreased from 88.3 to 87.0 kg from baseline to week 24 with mean change of - 1.3 kg (p < 0.001). The incidence and event rates of anytime confirmed (≤ 3.9 mmol/L) and/or severe hypoglycaemia were low: 7.7% and 0.42 events per patient-year, respectively. The overall Insulin Treatment Satisfaction Questionnaire (ITSQ) score increased from 53.2 to 78.2 from baseline to week 24 and the difference of 25.1 ± 21.5 points was significant (p < 0.001). CONCLUSIONS: In real-life settings, Gla-300 significantly improved glycaemic control and insulin treatment satisfaction in people with T2D who were inadequately controlled with NPH ± prandial insulin or premixed insulin analogues. Improvement of glycaemic control was associated with a very low risk of hypoglycaemia and with significant weight loss irrespective of the previous insulin regimen.

Insulinization in T2DM with Basal Analogues During COVID-19 Pandemic: Expert Opinion from an Indian Panel.

The ongoing global pandemic of the coronavirus disease 2019 (COVID-19) has placed a severe strain on the management of chronic conditions like diabetes. Optimal glycemic control is always important, but more so in the existing environment of COVID-19. In this context, timely insulinization to achieve optimal glycemic control assumes major significance. However, given the challenges associated with the pandemic like restrictions of movement and access to healthcare resources, a simple and easy way to initiate and optimize insulin therapy in people with uncontrolled diabetes is required. With this premise, a group of clinical experts comprising diabetologists and endocrinologists from India discussed the challenges and potential solutions for insulin initiation, titration, and optimization in type 2 diabetes mellitus (T2DM) during the COVID-19 pandemic and how basal insulin can be a good option in this situation owing to its unique set of advantages like lower risk of hypoglycemia, ease of training, need for less monitoring, better adherence, flexibility of using oral antidiabetic drugs, and improved quality of life compared to other insulin regimens. The panel agreed that the existing challenges should not be a reason to delay insulin initiation in people with uncontrolled T2DM and provided recommendations, which included potential solutions for initiating insulin in the absence or restriction of in-person consultations; the dose of insulin at initiation; the type of insulin preferred for simplified regimen and best practices for optimal titration to achieve glycemic targets during the pandemic. Practical and easily implementable tips for patients and involvement of stakeholders (caregivers and healthcare providers) to facilitate insulin acceptance were also outlined by the expert panel. Simplified and convenient insulin regimens like basal insulin analogues are advised during and following the pandemic in order to achieve glycemic control in people with uncontrolled T2DM.

Individualizing Time-in-Range Goals in Management of Diabetes Mellitus and Role of Insulin: Clinical Insights From a Multinational Panel.

Diabetes mellitus is a global health concern associated with significant morbidity and mortality. Inadequate control of diabetes leads to chronic complications and higher mortality rates, which emphasizes the importance of achieving glycemic targets. Although glycated hemoglobin (HbA1c) is the gold standard for measuring glycemic control, it has several limitations. Therefore, in recent years, along with the emergence of continuous glucose monitoring (CGM) technology, glycemic control modalities have moved beyond HbA1c. They encompass modern glucometrics, such as glycemic variability (GV) and time-in-range (TIR). The key advantage of these newer metrics over HbA1c is that they allow personalized diabetes management with person-centric glycemic control. Basal insulin analogues, especially second-generation basal insulins with properties such as longer duration of action and low risk of hypoglycemia, have demonstrated clinical benefits by reducing GV and improving TIR. Therefore, for more effective and accurate diabetes management, the development of an integrated approach with second-generation basal insulin and glucometrics involving GV and TIR is the need of the hour. With this objective, a multinational group of endocrinologists and diabetologists reviewed the existing recommendations on TIR, provided their clinical insights into the individualization of TIR targets, and elucidated on the role of the second-generation basal insulin analogues in addressing TIR.

Real-World Effectiveness of Insulin Glargine 300 Initiation in Switzerland.

INTRODUCTION: Insulin glargine 300 U/mL (Gla-300; Toujeo®) is a second-generation once-daily basal insulin. Previous randomized controlled trials showed comparable HbA1c reductions with lower rates of hypoglycemia of Gla-300 versus Gla-100. PATIENTS AND METHODS: We report the 12 months results of the Swiss cohort of Toujeo-1, a prospective, observational multicenter study exploring the real-world effectiveness of Gla-300 in adult patients with type 2 diabetes (T2D) uncontrolled (HbA1c 7.5-10%) on oral therapy and compared these to the overall Toujeo-1 cohort (conducted in Switzerland and Germany). Primary endpoint was the percentage of patients achieving individual HbA1c targets. Secondary endpoints included changes in HbA1c, fasting plasma glucose (FPG), body weight, insulin dose, incidence of hypoglycemia and overall safety. RESULTS: The analysis included 47 patients (14 women) with a mean age of 64.1 years and a diabetes duration of 8.4 years. Swiss physicians determined a higher HbA1c treatment target (7.4 vs. 7.0%) and patients received higher Gla-300 doses at baseline (20.2 vs. 14.7 units/day) and the 12-month follow-up (31.0 vs. 26.2 units/kg) than in the total cohort (n=721). After 12 months, the addition of Gla-300 reduced HbA1c by 1.5% (p<0.0001) to an HbA1c of 7.2%, and FPG by 3.3 mmol/L (p<0.0001) to an FPG of 7.1 mmol/L. At 12 months, 70.2% achieved their individual HbA1c target, more than in the overall Toujeo-1 cohort (49.9%). Body weight remained stable throughout. Only episodes of symptomatic, non-severe hypoglycemic events were documented (2.1%) with similar rates as for the overall Toujeo-1 population. CONCLUSION: In patients with T2D on oral therapy and newly treated with basal insulin, Gla-300 improves glycemic control with a low risk of hypoglycemia and no increase of body weight. The results for Switzerland are consistent with those reported for the overall Toujeo-1 cohort and reveal that treatment targets and approaches slightly differ between both countries.

Real-world safety and effectiveness of insulin glargine 300 U/mL in participants with type 2 diabetes who fast during Ramadan: The observational ORION study.

AIMS: ORION evaluated the safety and effectiveness of Gla-300 in insulin-treated people with T2DM before, during and after Ramadan, in a real-world setting. METHODS: This prospective, observational study across 11 countries included participants with T2DM treated with Gla-300 in pre-Ramadan, Ramadan and post-Ramadan periods. The primary endpoint was the percentage of participants experiencing ≥1 event of severe and/or symptomatic documented hypoglycaemia with self-monitored plasma glucose (SMPG) ≤70 mg/dL during Ramadan. Secondary endpoints included change in HbA1c and insulin dose and adverse events (AEs). RESULTS: The mean ± SD number of fasting days was 30.1 ± 3.2. The percentage of participants experiencing ≥1 event of severe and/or symptomatic documented hypoglycaemia (SMPG ≤70 [<54] mg/dL) was low in the pre-Ramadan (2.2% [0.8%]), Ramadan (2.6% [0%]) and post-Ramadan (0.2% [0%]) periods. No participants reported severe hypoglycaemia during Ramadan or post-Ramadan; one participant reported severe hypoglycaemia in pre-Ramadan. HbA1c fell pre- to post-Ramadan, and Gla-300 daily dose (mean ± SD) was reduced pre-Ramadan to Ramadan (from 25.6 ± 11.9 U/0.32 ± 0.14 U/kg to 24.4 ± 11.5 U/0.30 ± 0.13 U/kg). Incidence of AEs was 5.5%. CONCLUSIONS: In ORION, people with T2DM treated with Gla-300 who fasted during Ramadan had a low risk of severe/symptomatic hypoglycaemia and improved glycaemic control.

Insulin Glargine 300 U/mL and Insulin Glulisine Treatment in Patients with Type 2 Diabetes: A Non-Interventional Study of Effectiveness in Routine Clinical Practice.

INTRODUCTION: The EDITION development program confirmed that insulin glargine 300 U/mL (Gla-300) provides comparable glycemic control to insulin glargine 100 U/mL (Gla-100) but with lower hypoglycemia risk. Our study aimed to evaluate the effectiveness of Gla-300 in everyday practice. METHODS: This one-arm, non-interventional study included patients with type 2 diabetes who were switched to Gla-300-based basal-bolus therapy (BBT) and followed for 6 months. Indications for switching included inadequate glycemic control and/or hypoglycemic events with the previous regimen. RESULTS: Overall 229 patients were included, with mean age of 60.9 years. All glycemic variables improved between baseline and 6 months significantly (mean ± standard deviation [SD] hemoglobin A1c [HbA1c] from 8.9 ± 1.5% to 7.5 ± 1.1%, fasting blood glucose from 9.5 ± 3.1 mmol/L to 7.0 ± 2.1 mmol/L, postprandial blood glucose from 12.0 ± 3.8 mmol/L to 8.9 ± 2.5 mmol/L). Gla-300 doses were increased and mealtime insulin doses were unchanged. Rates of both non-severe and severe hypoglycemic events decreased significantly compared to pre-study and 6-month follow-up periods. Patients switched because of elevated HbA1c had higher baseline HbA1c and greater decrease in HbA1c paralleled with increase in insulin doses compared to those switched because of hypoglycemia. CONCLUSIONS: In day-to-day practice, switching from human insulin to Gla-300-based BBT resulted in significant improvement in glycemic control and decrease in hypoglycemia risk.