Second-generation Basal Insulin Analogues Research Articles

Expert Opinion on Current Trends in the Use of Insulin in the Management of People with Type 2 Diabetes from the South-Eastern European Region and Israel.

Despite the availability of various antihyperglycaemic therapies and comprehensive guidelines, glycaemic control in diabetes management has not improved significantly during the last decade in the real-world clinical setting. Treatment inertia arising from a complex interplay among patient-, clinician- and healthcare-system-related factors is the prime reason for this suboptimal glycaemic control. Also, the key factor leading to inadequate glycaemic levels remains limited communication between healthcare professionals (HCPs) and people with type 2 diabetes (PwT2D). Early insulin administration has several advantages including reduced glucotoxicity, high efficacy and preserved β-cell mass/function, leading to lowering the risk of diabetes complications. The current publication is based on consensus of experts from the South-Eastern European region and Israel who reviewed the existing evidence and guidelines for the treatment of PwT2D. Herein, the experts emphasised the timely use of insulin, preferably second-generation basal insulin (BI) analogues and intensification using basal-plus therapy, as the most-potent glucose-lowering treatment choice in the real-world clinical setting. Despite an increase in the use of glucagon-like peptide-1 receptor agonists (GLP-1 RAs), the experts urged timely insulin initiation for inadequate glycaemic control in PwT2D. Furthermore, the combination of BI and GLP-1 RA addressing both fasting plasma glucose and post-prandial excursions as a free- or fixed-ratio combination was identified to reduce treatment complexity and burden. To minimise discontinuation and improve adherence, the experts reiterated quality, regular interactions and discussions between HCPs and PwT2D/carers for their involvement in the diabetes management decision-making process. Clinicians and HCPs should consider the opinions of the experts in accordance with the most recent recommendations for diabetes management.

Trends in clinical characteristics, medication use, and glycemic control in insulin-treated patients with type 1 and type 2 diabetes in Finland in 2012-2019: Nationwide real-world evidence study.

To describe the clinical characteristics and medication purchases of insulin-treated adults in Finland at index (January 1, 2012 or first insulin purchase) and December 31, 2019. Additionally, to describe basal insulin (BI) treatment patterns and associated changes in hemoglobin A1c (HbA1c) values. In this descriptive study using nationwide registries, we included adults with at least two reimbursed insulin purchases within 12 months of the first purchase between January 1, 2012 and December 31, 2019. We formed four study groups: type 1 diabetes (T1D) and type 2 diabetes (T2D)-diagnosed people who were further divided into prevalent or naïve users (start of insulin use before or after January 1, 2012). Insulin treatment patterns were estimated from medication purchase data and glycemic control from HbA1c results. Out of 145 020 people included, 34 359 had T1D and 110 661 T2D. By 2019, in parallel with the adaptation of new noninsulin medications, second-generation basal insulin (BI) analogues were adopted by 45.9% and 21.1% of prevalent T1D and T2D users. At index, HbA1c target (≤53 mmol/mol) was reached by 17% and 35% of T2D naïve and prevalent users, respectively, and by 17% of T1D prevalent users. At study end, the target was reached respectively by 41%, 34%, and 22% of insulin users. Insulin initiation improved and discontinuation worsened glycemic control in T2D, with lesser effects seen after treatment gaps or switches between BIs. Our study showed that glycemic control in insulin users has remained stable or improved between 2012 and 2019 despite aging population and in parallel with introduction of new treatment options, providing valuable insight into Finnish national diabetes care.

Real-World Effects of Second-Generation Versus Earlier Intermediate/Basal Insulin Analogues on Rates of Hypoglycemia in Adults with Type 1 and 2 Diabetes (iNPHORM, US).

Second-generation basal insulin analogues have been shown to reduce hypoglycemia in several trials and observational studies of select populations; however, it remains unclear whether these results persist in real-world settings. Using self-reported hypoglycemia events, we assessed whether second-generation basal insulin analogues reduce rates of hypoglycemia events (non-severe/severe; overall/daytime/nocturnal) compared to earlier intermediate/basal insulin analogues among people with insulin-treated type 1 or 2 diabetes. We used prospectively collected data from the Investigating Novel Predictions of Hypoglycemia Occurrence Using Real-World Models (iNPHORM) panel survey. This US-wide, 1-year internet-based survey assessed hypoglycemia experiences and related sociodemographic and clinical characteristics of people with diabetes (February 2020-March 2021). We estimated population-average rate ratios for hypoglycemia comparing second-generation to earlier intermediate/basal insulin analogues using negative binomial regression, adjusting for confounders. Within-person variability of repeated observations was addressed with generalized estimating equations. Among iNPHORM participants with complete data, N = 413 used an intermediate/basal insulin analogue for ≥ 1month during follow-up. After adjusting for baseline and time-updated confounders, average second-generation basal insulin analogue users experienced a 19% (95% CI 3-32%, p = 0.02) lower rate of overall non-severe hypoglycemia and 43% (95% CI 26-56%, p < 0.001) a lower rate of nocturnal non-severe hypoglycemia compared to earlier intermediate/basal insulin users. Overall severe hypoglycemia rates were similar among second-generation and earlier intermediate/basal insulin users (p = 0.35); however, the rate of severe nocturnal hypoglycemia was reduced by 44% (95% CI 10-65%, p = 0.02) among second-generation insulin users compared to earlier intermediate/basal insulin users. Our real-world results suggest second-generation basal insulin analogues reduce rates of hypoglycemia, especially nocturnal non-severe and severe events. Whenever possible and feasible, clinicians should prioritize prescribing these agents over first-generation basal or intermediate insulin in people with type 1 and 2 diabetes.

Real-World Persistence, Adherence, Hypoglycemia, and Health Care Resource Utilization in People With Type 2 Diabetes Who Continued With the Second-Generation Basal Insulin Analog Insulin Glargine 300 Units/mL or Switched to a First-Generation Basal Insulin (Insulin Glargine 100 Units/mL or Detemir 100).

People with type 2 diabetes receiving a second-generation basal insulin (BI) analog may be switched to a first-generation formulation for financial reasons or changes in health insurance. However, because second-generation BI analogs have more even pharmacokinetic profiles, longer durations of action (>24 vs. ≤24 hours), and more stable action profiles than first-generation BI analogs, such a change may result in suboptimal treatment persistence and/or adherence. This study compared treatment persistence, treatment adherence, rates of hypoglycemia, and health care resource utilization outcomes in people with type 2 diabetes who either continued treatment with the second-generation BI Gla-300 or switched to a first-generation BI. The study showed that continuing with Gla-300 was associated with a lower risk of discontinuing therapy, fewer emergency department visits, and lower hypoglycemia event rates than switching to a first-generation BI.

Real-world Clinical Effectiveness on Glycaemic Parameters, Safety and Additional Benefits of Glargine U300 (Toujeo®) Initiation after Oral Antidiabetic Drug Failure in Insulin-naïve Patients with type 2 Diabetes Mellitus.

Several studies have proved the advantages of second-generation insulin analogs in lowering intra-individual variability in plasma insulin levels, flexibility in dosing, a sustained glucose-lowering effect, and decreasing the risk of hypoglycemia. Glargine 300 is one of the newer second-generation basal insulin analogs to have been approved for both type 1 and 2 diabetes. The present study aims to assess the real-world clinical effectiveness and safety of Glargine U300 (Toujeo®) initiation after oral antidiabetic drug failure in insulin-naïve patients with T2DM. A prospective, observational study was conducted where participants were interviewed regarding their basic demographics, body weight, and treatment details. Glycemic parameters (HbA1C%, Fasting Plasma Glucose, and Post Prandial Blood Glucose) were observed in the initial 6 months, and changes were noted and compared. Any hypoglycemic events or other complications were also noted. Data collected were statistically analyzed. The study included a total of 188 patients. Treatment with glargine 300 significantly reduced the mean HbA1C level from 9.78% at baseline to 7.90% at the end of 6 months of treatment (p < 0.001). 10.60% of patients achieved the glycemic target of ≤7.0% by the end of 6 months, while only 6.90% were within the target range at baseline. Similarly, significant reduction in FPG was observed at the end of 6 months treatment period with Glargine U300. A significant increase in dose requirement was observed throughout the study phase (p < 0.001). Incidence of hypoglycemia was noted in 2.12% of subjects. The lower incidence statistics of hypoglycemia coupled with sustained positive glycemic effects, stands out to be a prominent advantage of Glargine U300 over its other congeners.

Predictors of success and failure in achieving glycemic control targets in patients with type 2 diabetes on basal insulin: review of the real-world evidence studies

Basal insulin (BI) is the main therapeutic option for patients with type 2 diabetes (T2D) who have not reached glycemic targets on oral antidiabetic drugs and/or glucagon-like peptide-1 receptor agonists. The results of epidemiological studies indicate that the majority of patients with T2D do not achieve the targeted parameters of glycemic control on BI in the real-world settings. In this review the results of real-world evidence studies assessing predictors of success or failure of BI therapy in patients with T2D are we summarized. A number of studies have demonstrated that delayed initiation of insulin therapy with a high level of glycated hemoglobin A1c (HbA1c) at the start of the treatment reduces achieving glycemic control targets on BI. Hypoglycemia in the first weeks or months of BI treatment may reduce the adherence and persistence to treatment and likelihood of achieving treatment targets. In real-world evidence studies, glargine 300 U/mL and degludec, the long-acting second-generation insulin analogues, have shown greater potential in reduction of HbA1c levels with a lower risk of hypoglycaemia compared to other BIs. In the DUNE, ATOS, and some others studies, a lack of insulin dose titration in newly initiated BI users and those who needed treatment intensification was demonstrated. Poor treatment adherence and persistence (missed injections, incorrect dose selection, and temporary or permanent discontinuation of insulin therapy), deviations in insulin injection technique, and formation of lipohypertrophy at the injection sites are also common problems that prevent good glycemic control in these patients. Therefore, patient education with a focus on injection technique, dose titration and prevention of hypoglycemia, as well as the use of the second-generation BI analogs, increases the chances for achieving glycemic control targets in patients with T2D who initiate or need to intensify BI therapy.

105-LB: Glucose Variability with Second-Generation Basal Insulin Analogs Glargine 300 U/mL and Degludec 100 U/mL, Evaluated by CGM in People with T1D—The InRange Randomized Controlled Trial

Background: InRange has previously demonstrated that insulin glargine 300 U/mL (Gla-300) is non-inferior to insulin degludec 100 U/mL (IDeg-100) in terms of time in glucose range 70--180 mg/dL (primary endpoint) and total glucose coefficient of variation (CV) as measured by CGM in people with T1D. Methods: InRange (NCT04075513) was a multicenter, randomized, active-controlled, parallel-group, 12-week open-label trial comparing Gla-300 vs. IDeg-100 in adults with T1D using 20-day CGM profiles (≥10 days evaluable) . Here we present data for within- and between-day CV. Results: Overall, 343 participants were randomized (172 Gla-300, 171 IDeg-100) : mean ± SD age was 42.8 ± 13.3 years and T1D duration was 20.5 ± 12.8 years. Both within-day and between-day glucose CV at Week 12 were similar with Gla-300 and IDeg-100 (Table) . Within-day glucose CV at Week 12 was below the threshold for glycemic stability (36%) in both groups and was also similar in both treatment groups irrespective of glycemic stability at baseline (CV ≤36% or &amp;gt;36%) . The LS mean within-day glucose CV of participants with CV &amp;gt;36% at baseline reached 33.67 (Gla-300) and 35.38 (IDeg-100) at Week 12. Conclusion: Using clinically relevant CGM metrics, InRange shows that Gla-300 and IDeg-100 provide similar within- and between-day glucose variability in people with T1D. Disclosure R. M. Bergenstal: Advisory Panel; Hygieia, Medtronic, Roche Diabetes Care, Zealand Pharma A/S, Consultant; Abbott Diabetes, Ascensia Diabetes Care, Bigfoot Biomedical, Inc., CeQur SA, Dexcom, Inc., Eli Lilly and Company, Novo Nordisk, Onduo LLC, Sanofi, United HealthCare Services, Inc., Research Support; Abbott Diabetes, Dexcom, Inc., Eli Lilly and Company, Insulet Corporation, Medtronic, Novo Nordisk, Sanofi. T. Battelino: Advisory Panel; Abbott Diabetes, Indigo Diabetes, Lilly Diabetes, Medtronic, Novo Nordisk, Sanofi, Research Support; Medtronic, Novartis Pharmaceuticals Corporation, Novo Nordisk, Zealand Pharma A/S, Speaker’s Bureau; Abbott Diabetes, Dexcom, Inc., Lilly Diabetes, Medtronic, Novo Nordisk, Sanofi, Stock/Shareholder; DreaMed Diabetes, Ltd. S. Edelman: Consultant; Abbott Diabetes, Lilly Diabetes, Sanofi-Aventis U. S., Xeris Pharmaceuticals, Inc. P. Choudhary: Advisory Panel; Abbott Diabetes, Lilly Diabetes, Medtronic, Research Support; Novo Nordisk, Speaker’s Bureau; Dexcom, Inc., Glooko, Inc., Insulet Corporation, Sanofi. T. Danne: Consultant; Abbott, AstraZeneca, Boehringer Ingelheim International GmbH, Dexcom, Inc., Lilly, Medtronic, Novo Nordisk, Roche Pharmaceuticals, Sanofi, Ypsomed AG, Research Support; Abbott, AstraZeneca, Boehringer Ingelheim International GmbH, Dexcom, Inc., Lilly, Medtronic, Novo Nordisk, Roche Pharmaceuticals, Sanofi, Ypsomed AG, Stock/Shareholder; DreaMed Diabetes, Ltd. E. Renard: Consultant; Abbott, AstraZeneca, Boehringer Ingelheim International GmbH, Dexcom, Inc., Insulet Corporation, LifeScan, Lilly, Novo Nordisk, Roche Diabetes Care, Sanofi, Tandem Diabetes Care, Inc. J. Westerbacka: Employee; Sanofi, Stock/Shareholder; Sanofi. B. Mukherjee: Employee; Sanofi, Stock/Shareholder; Sanofi. P. Picard: n/a. V. Pilorget: None. Funding Sanofi

Clinical Use of Insulin Glargine 300U/mL in Adults with Type2 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.Supplementary InformationThe online version contains supplementary material available at 10.1007/s13300-022-01247-7.

Weekly Insulin Becoming a Reality

Insulin was first isolated in 1921 and developed as a therapeutic agent in the 1920s. The initial crude preparations were injected multiple times daily because of their short duration of action. Consequently, there were many attempts to develop insulin preparations with prolonged biological availability in the hope that less frequent once-daily administration would be feasible (1). A host of such preparations were introduced, including protamine insulin, protamine zinc insulin, surfen insulin, globin insulin, iso-insulin, isophane insulin (NPH), and insulin zinc suspensions (lente insulins) (1) (Fig. 1). The goal was mainly to reduce the number of injections and thus the patient burden. Yet, with the development of a radioimmunoassay for insulin (2), it became apparent that physiologic insulin secretion involved two components: meal-related insulin secretion with postprandial spikes and basal insulin secretion that remains relatively constant with some minor pulsatility (3). Subsequently, as modern insulin therapy evolved, facilitated by patient self-monitoring of blood glucose (4,5), it became apparent that the inherent peaks in basal insulin preparations, such as with the nonsoluble NPH or lente insulins, created risk of hypoglycemia, especially if the insulin vials were not correctly rolled to create a proper suspension. Moreover, these insulins did not have sufficiently long duration of action to be used once daily. Consequently, in addition to making them soluble, two of the goals in development of basal insulin analogs, such as insulin glargine and insulin detemir, were to eliminate insulin peaks and to prolong the action to approach 24 h (6,7). Second-generation basal insulin analogs, such as insulin degludec and insulin glargine U300, came with …

Insulin doses requirements in patients with type 1 diabetes using glargine U300 or degludec in routine clinical practice

There are not many real-world studies evaluating daily insulin doses requirements (DIDR) in patients with type 1 diabetes (T1D) using second-generation basal insulin analogs, and such comparison is necessary. The...

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.

Considerations for Insulin-Treated Type 2 Diabetes Patients During Hospitalization: A Narrative Review of What We Need to Know in the Age of Second-Generation Basal Insulin Analogs.

With the availability of second-generation basal insulin analogs, insulin degludec (100 and 200 units/ml [degludec]) and insulin glargine 300 units/ml (glargine U300), clinicians now have long-acting, efficacious treatment options with stable pharmacokinetic profiles and associated low risks of hypoglycemia that may be desirable for many patients with type 2 diabetes. In this narrative review, we summarize the current evidence on glycemic control in hospitalized patients and review the pharmacokinetic properties of degludec and glargine U300 in relation to the challenges these may pose during the hospitalization of patients with type 2 diabetes who are receiving outpatient regimens involving these newer insulins. Their increased use in clinical practice requires that hospital healthcare professionals (HCPs) have appropriate protocols to transfer patients from these second-generation insulins to formulary insulin on admission, and ensure the safe discharge of patients and transition back to degludec or glargine U300. However, there is no guidance available on this. Based on the authors’ clinical experience, we identify key issues to consider when arranging hospital care of such patients. We also summarize the limited available evidence on the potential utility of these second-generation basal insulin analogs in the non-critical inpatient setting and identify avenues for future research. To address current knowledge gaps, it is important that HCPs are educated about the differences between standard formulary insulins and second-generation insulins, and the importance of clear communication during patient transitions.

The Safety and Efficacy of Second-Generation Basal Insulin Analogues in Adults with Type 2 Diabetes at Risk of Hypoglycemia and Use in Other Special Populations: A Narrative Review.

Hypoglycemia is a major barrier impeding glycemic control in persons with type 2 diabetes mellitus and creates a substantial burden on the healthcare system. Certain populations that require special attention, such as older adults and individuals with renal impairment, a longer duration of diabetes or those who have experienced prior hypoglycemia, may be at a higher risk of hypoglycemia, particularly with insulin treatment. Second-generation basal insulin analogues (insulin glargine 300 U/mL and degludec) have demonstrated reductions in hypoglycemia compared with insulin glargine 100 U/mL although evidence of this benefit across specific populations is less clear. In this review we summarize the literature with respect to the efficacy and safety data for second-generation basal insulin analogues in adults with type 2 diabetes mellitus who are at risk of hypoglycemia or who require special attention. Randomized controlled trials, meta-analyses and real-world evidence demonstrate that the use of second-generation basal insulin analogues is associated with less hypoglycemia compared with insulin glargine 100 U/mL without compromising glycated hemoglobin control. A reduced risk of hypoglycemia with second-generation basal insulin analogues was evident in older adults and in individuals with obesity, renal impairment, a history of cardiovascular disease or a long duration of insulin use. Further studies are needed in other populations, including those with more severe renal impairment or hepatic dysfunction, the hospitalized population and those with cognitive impairment. Overall, less hypoglycemia associated with second-generation basal insulin analogues may help reduce barriers for insulin use, improve adherence and offset the costs of hypoglycemia-related healthcare resource utilization.

Insulin glargine 300 U/mL and insulin degludec: A review of the current evidence comparing these two second-generation basal insulin analogues.

For most people with type 2 diabetes (T2D), treatment intensification with the addition of basal insulin therapy is required to maintain glycaemic control. However, this often does not happen in real-life practice promoting the development of long-term diabetes-related complications. The second-generation basal insulin analogues glargine 300 U/mL (Gla-300) and degludec (IDeg) provide pharmacokinetic and pharmacodynamic improvements that may allow them to be more effective in appropriately managing diabetes compared with first-generation basal insulin analogues. Both Gla-300 and IDeg have been extensively studied vs the first-generation basal insulin glargine 100 U/mL, demonstrating comparable efficacy in terms of glycaemic control, and a lower risk of hypoglycaemia. The BRIGHT randomized controlled trial is the first direct comparison of the efficacy and safety profiles of Gla-300 and IDeg in patients with T2D. Moreover, real-world data have been used to assess the effectiveness of these basal insulins during routine clinical practice. Further research is required to determine if the properties of Gla-300 and IDeg may lead to improvements in healthcare-related costs and the quality of life of patients, which are important factors for informing clinical decisions.

Glargine-300: An updated literature review on randomized controlled trials and real-world studies.

Despite the availability of a variety of insulins, rates of insulinisation and the acceptance of insulin therapy is suboptimal in real-world clinical settings. Patient and physician concerns with hypoglycaemia and weight gain are the two key issues that serve to impede appropriate insulinisation in patients with diabetes. Recently introduced second-generation basal insulin analogues [for e.g., insulin glargine 300 U/mL (Gla-300) and insulin degludec] are designed to have improved pharmacokinetic profiles with an intention to deliver steady insulin levels over a longer period. Several randomised controlled and real-world studies have proven the resultant advantages of second-generations insulin analogues in lowering intra-individual variability in plasma insulin levels, flexibility in dosing, a sustained glucose-lowering effect, and decreasing the risk of hypoglycaemia. Gla-300 is one of the newer second-generation basal insulin analogues to have been approved for both type 1 and 2 diabetes. In this article, we review the currently available clinical and real-world data of Gla-300.

Switching from Neutral Protamine Hagedorn Insulin to Insulin Glargine 300 U/mL Improves Glycaemic Control and Reduces Hypoglycaemia Risk: Results of a Multicentre, Prospective, Observational Study.

Type 2 diabetes mellitus (T2DM) is a major cause of morbidity and mortality worldwide and is an important public health issue. A significant proportion of insulin-treated patients with T2DM do not reach target glycated haemoglobin (HbA1c) values, which ultimately increases their risk of long-term microvascular and macrovascular complications. One potential option to improve diabetes control in these patients may be the use of new insulin formulations including second-generation basal insulin analogues such as insulin glargine 300 U/mL (Gla-300). Several published randomised controlled trials have assessed the clinical effectiveness of Gla-300, mostly versus insulin glargine 100 U/mL as well as insulin degludec. However, there is limited information about the real-world effectiveness of Gla-300 when patients are transitioned directly from neutral protamine Hagedorn (NPH) human basal insulin. The primary objective of this study was to evaluate the effectiveness of Gla-300, defined as the percentage of participants with an HbA1c reduction of ≥0.5%, 6 months after switching from NPH insulin, in participants with T2DM. Secondary objectives included the safety assessment based on the percentage of patients experiencing ≥1 episodes and the number of hypoglycaemic episodes by category: severe, symptomatic, symptomatic confirmed, diurnal or nocturnal, change in body weight, and insulin dose. A total of 469 participants completed the 6-month observation period. Mean baseline HbA1c was 9.19%. The percentage of participants with a ≥0.5% improvement in HbA1c from baseline was 71.7% at 6 months. Mean HbA1c decreased at 3 and 6 months by 0.77% (±0.98) and 1.01% (±1.12), respectively (p < 0.00001 versus baseline), while fasting glycaemia decreased by 32 mg/dL and 37 mg/dL, respectively (p < 0.00001 versus baseline). There were moderate increases in the doses of both Gla-300 and, if used, short-acting insulins during the 6 months of observation. The percentage of participants with ≥1 hypoglycaemia event during the preceding 4 weeks decreased significantly from baseline to 3 and 6 months, as did the proportion with symptomatic hypoglycaemia at night (p < 0.00001 versus baseline). No participants had severe hypoglycaemia after a switch to Gla-300. Body mass, waist and hip circumferences, and waist : hip ratio did not change significantly. In conclusion, this large, prospective, observational study demonstrated that switching from NPH insulin to Gla-300 resulted in a significant improvement in HbA1c, with only a moderate increase in insulin dose, a decreased risk of hypoglycaemia, and no increase in body weight.

InRange: Comparison of the Second-Generation Basal Insulin Analogues Glargine 300 U/mL and Degludec 100 U/mL in Persons with Type 1 Diabetes Using Continuous Glucose Monitoring-Study Design.

IntroductionSuboptimal glycaemic control among people with type 1 diabetes (T1D) is known to lead to long-term micro- and macrovascular complications and, unfortunately, it is still prevalent even in the most affluent societies. Although glycated haemoglobin monitoring is considered to be the gold standard for assessing glycaemic control, such monitoring is unable to reliably measure acute glycaemic excursions. Continuous glucose monitoring (CGM) has been shown to improve glucose control and reduce the incidence of hypoglycaemia, and also allow a more complete assessment of overall glycaemic control and hyper- and hypoglycaemic excursions. The use of CGM has led to time-in-range, which is the time that a patient is within the glycaemic range of 70 to 180 mg/dL, to be adopted as a treatment target. To date, only limited data comparing the second-generation insulins glargine 300 U/mL (Gla-300) and degludec 100 U/mL (IDeg-100) in people with T1D are available, and there is no CGM literature on comparisons of the use of CGM results to assess primary, secondary and tertiary endpoints. The aim of the InRange study was to address this unmet need.MethodsInRange is a multicentre, randomised, active-controlled, parallel-group, 12-week, open-label, phase 4, comparative study. Adults with T1D will be randomised to receive once-daily Gla-300 or IDeg-100 by subcutaneous injection in the morning. Following an 8-week titration period, CGM data will be collected over 20 consecutive days.Planned outcomesThe primary objective is to demonstrate that Gla-300 is noninferior to IDeg-100 in terms of glycaemic control [time-in-range ≥ 70 to ≤ 180 mg/dL (≥ 3.9 to ≤ 10 mmol/L)] and variability, as assessed using CGM, in adults with T1D. The results are expected to help confirm the utility of CGM in clinical practice in this population and provide insight into its application as an outcome measure in clinical practice.Trial registrationNCT04075513. Video Electronic Supplementary MaterialThe online version of this article (10.1007/s13300-020-00781-6) contains supplementary material, which is available to authorized users.

Improving Type 2 Diabetes Management in General Practice Using a Second-Generation Basal Insulin Analogue Insulin Glargine 300U/mL: A Practical Guide.

Type 2 diabetes management can be improved by the use of second-generation basal insulin analogues as the first choice on commencement of insulin, in this instance focussing on insulin glargine 300 U/mL (Gla-300). The clinical application of the use of Gla-300 include advantages such as less intra- and interpatient variability in glucose control resulting in rather less hypoglycaemia, longer duration of action and greater flexibility in the timing of administration thus suiting a wide range of patient presentations.Funding: Sanofi Australia.

1095-P: Early Hypoglycemia after Initiation of Second-Generation Basal Insulin (BI) Analogs: Patient Characteristics and Clinical Outcomes

Titration following initiation of BI tends to occur in the first 8-12 weeks. At this time, patients may be at risk of experiencing hypoglycemia, which itself may present a barrier to optimal glycemic control. BRIGHT was the first randomized controlled trial comparing efficacy and safety of two second-generation BI analogs in insulin-naïve patients with T2DM, and showed less hypoglycemia with insulin glargine 300 U/mL (Gla-300) vs. insulin degludec 100 U/mL (IDeg) in the initial 12-week titration period. We investigated patient characteristics and clinical outcomes (including HbA1c change, and hypoglycemia incidence during weeks 13-24) by the occurrence of early confirmed (≤70 mg/dL) hypoglycemia (in the titration period) using descriptive statistics. Participants experiencing hypoglycemia within the first 12 weeks tended to be older, had lower BMI, more impaired renal function, longer duration of diabetes, and were more likely to be using SUs at baseline (Table). Overall, hypoglycemia incidence during weeks 13-24 was lower in the group that did not experience hypoglycemia within the first 12 weeks. HbA1c reductions at week 12 were greater in those with hypoglycemia in the titration period. These findings suggest that patients experiencing early hypoglycemia with second-generation BI analogs have increased hypoglycemia risk in later stages of therapy. Disclosure S.B. Harris: Advisory Panel; Self; AstraZeneca, Janssen Pharmaceuticals, Inc., Lilly/Boehringer Ingelheim, Merck &amp; Co., Inc., Novo Nordisk A/S, Sanofi. Consultant; Self; AstraZeneca, Janssen Pharmaceuticals, Inc., Lilly/Boehringer Ingelheim, Merck &amp; Co., Inc., Novo Nordisk Inc., Sanofi. Research Support; Self; Abbott, AstraZeneca, Janssen Pharmaceuticals, Inc., Merck &amp; Co., Inc., Novo Nordisk A/S, Sanofi. Other Relationship; Self; Canadian Diabetes Association, Canadian Institutes of Health Research, The Lawson Foundation. L. Berard: Advisory Panel; Self; Eli Lilly and Company. Consultant; Self; Abbott, Ascensia Diabetes Care, AstraZeneca, Bayer AG, Becton, Dickinson and Company, Janssen Pharmaceuticals, Inc., LifeScan Canada, Mylan, Novo Nordisk Inc., Sanofi. Research Support; Self; Montmed Inc. Speaker's Bureau; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Merck &amp; Co., Inc. J. Westerbacka: Employee; Self; Sanofi. Stock/Shareholder; Self; Sanofi. Z. Bosnyak: Employee; Self; Sanofi. Stock/Shareholder; Self; Sanofi. L. Melas-Melt: Consultant; Self; Sanofi. F. Lauand: Employee; Self; Sanofi. T.S. Bailey: Advisory Panel; Self; Abbott. Consultant; Self; Capillary Biomedical, Inc., Eli Lilly and Company, Medtronic, Novo Nordisk Inc., Sanofi. Research Support; Self; Abbott, Ascensia Diabetes Care, Becton, Dickinson and Company, Boehringer Ingelheim Pharmaceuticals, Inc., Calibra Medical, Capillary Biomedical, Inc., Companion Medical, Dance Biopharm Holdings Inc., Dexcom, Inc., Diasome Pharmaceuticals, Inc., Eli Lilly and Company, GlySens Incorporated, Kowa Pharmaceutical Europe Co. Ltd., Lexicon Pharmaceuticals, Inc., Medtronic, Novo Nordisk Inc., POPS! Diabetes Care, POPS! Diabetes Care, Sanofi, Senseonics, vTv Therapeutics, Xeris Pharmaceuticals, Inc., Zealand Pharma A/S. Speaker's Bureau; Self; Abbott, MannKind Corporation, Medtronic, Novo Nordisk Inc., Sanofi US, Senseonics. K. Khunti: Advisory Panel; Self; Amgen Inc., AstraZeneca, Eli Lilly and Company, Merck Sharp &amp; Dohme Corp., Novo Nordisk A/S, Sanofi. Consultant; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Janssen Pharmaceuticals, Inc., Merck Sharp &amp; Dohme Corp., Novartis AG, Novo Nordisk A/S, Pfizer Inc., Sanofi-Aventis, Servier, Takeda Pharmaceutical Company Limited. Research Support; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Merck Sharp &amp; Dohme Corp., Novartis AG, Novo Nordisk A/S, Pfizer Inc., Sanofi-Aventis. Speaker's Bureau; Self; AstraZeneca, Berlin-Chemie AG, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Janssen Pharmaceuticals, Inc., Menarini Group, Merck Sharp &amp; Dohme Corp., Novartis AG, Novo Nordisk A/S, Roche Pharma, Sanofi, Servier, Takeda Pharmaceutical Company Limited. Funding Sanofi (NCT02738151)

1090-P: Reaching ADA Glycemic Targets without Hypoglycemia during Titration with Gla-300 and IDeg in T2DM: Exploratory Analyses from BRIGHT

Guidelines emphasize achieving glycemic targets without hypoglycemia. BRIGHT demonstrated similar HbA1c reduction and less anytime (24 h) hypoglycemia with insulin glargine 300 U/mL (Gla-300) vs. insulin degludec 100 U/mL (IDeg) during the initial 12-week insulin titration period, in insulin-naïve adults with T2DM. We investigated achievement of ADA-recommended HbA1c and fasting self-monitored plasma glucose (FSMPG) targets without confirmed (≤70 mg/dL) hypoglycemia in the first 12 weeks. BRIGHT was a 24-week, multicenter, open-label, randomized, active-controlled, parallel-group, phase 4 trial. Participants were randomized to Gla-300 (n=466) or IDeg (n=463), titrated to a FSMPG of 80-100 mg/dL (below ADA-recommended FSMPG target of ≤130 mg/dL). A similar proportion of participants at week 8 achieved HbA1c &amp;lt;7% without hypoglycemia in both groups; this proportion was numerically higher with Gla-300 than IDeg at week 12 (16.9% vs. 13.6%). From baseline to week 5, numerically more patients with IDeg achieved FSMPG ≤130 mg/dL without hypoglycemia vs. Gla-300, but from week 6 to 12 this was reversed (Figure). More participants achieved ADA-recommended glycemic targets without hypoglycemia with Gla-300 vs. IDeg during the titration period of BRIGHT. These second-generation basal insulin analogs may allow more aggressive titration after insulin initiation in T2DM. Disclosure R. Roussel: Advisory Panel; Self; Merck Sharp &amp; Dohme Corp., Sanofi. Consultant; Self; Abbott, AstraZeneca, Eli Lilly and Company, Medtronic, Novo Nordisk A/S, Physiogenex. Research Support; Self; Janssen Pharmaceuticals, Inc. J.P. Frias: Advisory Panel; Self; Becton, Dickinson and Company, Eli Lilly and Company, Gilead Sciences, Inc., Sanofi. Consultant; Self; Echosens, Genentech, Inc., Johnson &amp; Johnson Diabetes Institute, Novo Nordisk Inc., Zafgen, Inc. Research Support; Self; AbbVie Inc., Akcea Therapeutics, Allergan, Amgen Inc., AstraZeneca, Bayer US, Boehringer Ingelheim Pharmaceuticals, Inc., Bristol-Myers Squibb Company, Cirius Therapeutics, Elcelyx Therapeutics, Inc., Eli Lilly and Company, Enanta Pharmaceuticals, Inc., GENFIT, Intarcia Therapeutics, Inc., Intercept Pharmaceuticals, Inc., Ionis Pharmaceuticals, Inc., Janssen Pharmaceuticals, Inc., Merck &amp; Co., Inc., NGM Biopharmaceuticals, Novartis Pharmaceuticals Corporation, Novo Nordisk A/S, Oramed Pharmaceuticals, Pfizer Inc., Sanofi, TaiwanJ Pharmaceuticals Co., Ltd., Theracos, Inc. Speaker's Bureau; Self; Merck &amp; Co., Inc., Sanofi. J. Westerbacka: Employee; Self; Sanofi. Stock/Shareholder; Self; Sanofi. Z. Bosnyak: Employee; Self; Sanofi. Stock/Shareholder; Self; Sanofi. L. Melas-Melt: Consultant; Self; Sanofi. L. Berard: Advisory Panel; Self; Eli Lilly and Company. Consultant; Self; Abbott, Ascensia Diabetes Care, AstraZeneca, Bayer AG, Becton, Dickinson and Company, Janssen Pharmaceuticals, Inc., LifeScan Canada, Mylan, Novo Nordisk Inc., Sanofi. Research Support; Self; Montmed Inc. Speaker's Bureau; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Merck &amp; Co., Inc. A.Y. Cheng: Advisory Panel; Self; Abbott, AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, HLS Therapeutics, Janssen Pharmaceuticals, Inc., Merck &amp; Co., Inc., Novo Nordisk A/S, Sanofi. Research Support; Self; Boehringer Ingelheim International GmbH, Sanofi. Speaker's Bureau; Self; Abbott, AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Janssen Pharmaceuticals, Inc., mdBriefCase Group Inc., Merck &amp; Co., Inc., Novo Nordisk A/S, Sanofi. Funding Sanofi (NCT02738151)