Second-generation Basal Insulin Research Articles

Basal Insulinotherapy in Patients Living with Diabetes in France: The EF-BI Study.

Second-generation basal insulins like glargine 300U/mL (Gla-300) have a longer duration of action and less daily fluctuation and interday variability than first-generation ones, such as glargine 100U/mL (Gla-100). The EF-BI study, a nationwide observational, retrospective study, was designed to compare persistence, acute care complications, and healthcare costs associated with the initiation of such basal insulins (BI) in a real-life setting in France. This study was conducted using the French healthcare claims database (SNDS). Adult patients living with type1 or type2 diabetes mellitus (T1DM or T2DM) initiating Gla-300 or Gla-100 ± other hypoglycemic medications between January 1, 2016 and December 31, 2020, and without any insulin therapy over the previous 6months were included. Persistence was defined as remaining on the same insulin therapy until discontinuation defined by a 6 month period without insulin reimbursement. Hospitalized acute complications were identified using ICD-10 codes. Total collective costs were established for patients treated continuously with each basal insulin over 1-3years. All comparisons were adjusted using a propensity score based on initial patient/treatment characteristics. A total of 235,894 patients with T2DM and 6672 patients with T1DM were included. Patients treated with Gla-300 were 83% (T1DM) and 44% (T2DM) less likely to discontinue their treatment than those treated with Gla-100 after 24months (p < 0.0001). The annual incidence of acute hospitalized events in patients with T2DM treated with Gla-300 was 12% lower than with Gla-100 (p < 0.0001) but similar in patients with T1DM. Comparison of overall costs showed moderate but statistically significant differences in favor of Gla-300 versus Gla-100 for all patients over the first year, and in T2DM only over a 3-year follow-up. Use of Gla-300 resulted in a better persistence, less acute hospitalized events at least in T2DM, and reduced healthcare expenditure. These real-life results confirmed the potential interest of using Gla-300 rather than Gla-100.

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.

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

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

818-P: Glycemic Control in Naïve Users of Second-Generation Basal Insulins with T2D and CKD—A Nationwide Register-Based Cohort Study

Objective: We aimed to compare the effectiveness and safety of second-generation basal insulins, insulin glargine 300 U/mL (Gla-300) and insulin degludec 100 U/mL (Deg-100), in terms of change in HbA1c, hospitalization for hypoglycemia and all-cause mortality. Methods: In this register-based cohort study, using real-word data on the entire Danish diabetes population in the period 2013-2020, we included 6519 naïve users of Gla-300 or Deg-100 with T2D and chronic kidney disease (CKD). Change in HbA1c, from initiation of either study drugs to end of follow-up, was modeled with mixed-effect models while rates of hospitalization for hypoglycemia and all-cause mortality were modeled in separate Poisson models. Results: Mean HbA1c levels were reduced by 13-14 mmol/mol over a four-year period in both groups with no significant difference (Figure). The rate of hospitalization for hypoglycemia was slightly but not significantly higher in the Deg-100 group (rate-ratio 1.03 (CI 95%: 0.71, 1.49) while the all-cause mortality rate was slightly but not significantly lower in the Deg-100 group (0.97 (0.83, 1.14)). Conclusion: We found no difference in HbA1c reduction, hospitalization for hypoglycemia or all-cause mortality between Gla-300 and Deg-100, in a real-world population of naïve users with T2D and CKD. Disclosure V.Kosjerina: Research Support; Sanofi-Aventis Deutschland GmbH. B.Carstensen: Stock/Shareholder; Novo Nordisk. H.Amadid: Employee; Novo Nordisk A/S. D.Vistisen: Research Support; Bayer Inc., Sanofi, Boehringer-Ingelheim, Stock/Shareholder; Novo Nordisk A/S. Funding Sanofi-Aventis Deutschland GmbH

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.

New indication for long-acting second-generation basalinsulin analog?

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Second Generation Basal Insulin, Degludec, in the Management of Diabetes; Consensus Report

The best anti-diabetic medication does, in fact, have a low propensity to increase body weight and rate of hypoglycemia as well as glycemic control. The second-generation basal insulins analogues insulin degludec and insulin glargine 300 units/mL have significantly longer half-life and substantially smoother profiles than firstgeneration. The duration of action of glargine 300 is shorter than that of degludec, and significant residual glycemic variability is still present. Degludec has lower risks of hypoglycemia. Evaluating the therapeutic application in various geographical contexts is necessary, given the inter-country variations in the prescription patterns of glucose-lowering medications for persons with diabetes. A Saudi task force gathered to develop an explicit, evidence-based consensus for insulin degludec utilization in the local setting. This work contains the expert panel's recommendations as a contribution to complement the knowledge gap in this area from the national perspective. Results of the local UPDATES study investigating the treatment effect of degludec in adults with T2DM in Saudi Arabia showed that patients treated with degludec experienced clinically significant improvements in glycaemic control and a lower rate of hypoglycemia compared to baseline, with no new safety concerns. Results confirm that previously published data with degludec are generalizable to a broad population of patients with T2DM in routine clinical practice in Saudi Arabia. Moreover, local cost-utility analyses of degludec versus glargine 300 in T1DM and T2DM showed that it is cost-saving. Degludec was associated with less cost with better quality of life. Thus, the reimbursement of degludec will have a positive impact on the budget.

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.

Insulin degludec versus insulin detemir, both in combination with insulin aspart, in the treatment of pregnant women with type 1 diabetes (EXPECT): an open‑label, multinational, randomised, controlled, non-inferiority trial

Insulin degludec (degludec) is a second-generation basal insulin with an improved pharmacokinetic-pharmacodynamic profile compared with first-generation basal insulins, but there are few data regarding its use during pregnancy. In this non-inferiority trial, we aimed to compare the efficacy and safety of degludec with insulin detemir (detemir), both in combination with insulin aspart (aspart), in pregnant women with type 1 diabetes. This open-label, multinational, randomised, controlled, non-inferiority trial (EXPECT) was conducted at 56 sites (hospitals and medical centres) in 14 countries. Women aged at least 18 years with type 1 diabetes who were between gestational age 8 weeks (+0 days) and 13 weeks (+6 days) or planned to become pregnant were randomly assigned (1:1), via an interactive web response system, to degludec (100 U/mL) once daily or detemir (100 U/mL) once or twice daily, both with mealtime insulin aspart (100 U/mL), all via subcutaneous injection. Participants who were pregnant received the trial drug at randomisation, throughout pregnancy and until 28 days post-delivery (end of treatment). Participants not pregnant at randomisation initiated the trial drug before conception. The primary endpoint was the last planned HbA1c measurement before delivery (non-inferiority margin of 0·4% for degludec vs detemir). Secondary endpoints included efficacy, maternal safety, and pregnancy outcomes. The primary endpoint was assessed in all randomly assigned participants who were pregnant during the trial. Safety was assessed in all randomly assigned participants who were pregnant during the trial and exposed to at least one dose of trial drug. This study is registered with ClinicalTrials.gov, NCT03377699, and is now completed. Between Nov 22, 2017, and Nov 8, 2019, from 296 women screened, 225 women were randomly assigned to degludec (n=111) or detemir (n=114). Mean HbA1c at pregnancy baseline was 6·6% (SD 0·6%; approximately 49 mmol/mol; SD 7 mmol/mol) in the degludec group and 6·5% (0·8%; approximately 48 mmol/mol; 9 mmol/mol) in the detemir group. Mean last planned HbA1c measurement before delivery was 6·2% (SE 0·07%; approximately 45 mmol/mol; SE 0·8 mmol/mol) in the degludec group and 6·3% (SE 0·07%; approximately 46 mmol/mol; SE 0·8 mmol/mol) in the detemir group (estimated treatment difference -0·11% [95% CI -0·31 to 0·08]; -1·2 mmol/mol [95% CI: -3·4 to 0·9]; pnon-inferiority<0·0001), confirming non-inferiority. Compared with detemir, no additional safety issues were observed with degludec. In pregnant women with type 1 diabetes, degludec was found to be non-inferior to detemir. Novo Nordisk.

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.

ATOS study: effectiveness and safety of insulin glargine 300 U/mL in the real world clinical practice in insulin-naïve type 2 diabetic patients in the Russian Federation

Rationale: Basal insulin glargine 300 U/mL (Gla-300) is a second-generation basal insulin analogue that has comparable efficacy and lower variability compared to the first generation long-acting insulin analogue glargine 100 U/mL.&#x0D; Aim: To assess the effectiveness and safety of Gla-300 in insulin-nave type 2 diabetic patients in the real world practice in Russia.&#x0D; Materials and methods: ATOS (NCT03703869) was a 12-month, prospective observational international multicenter study. The study included 4422 adults ( 18 years) with uncontrolled type 2 diabetes (HbA1c 7 and 11%) with 1 oral anti-hyperglycemic drug and for whom the treating physician had decided to add Gla-300. We performed a post-hoc sub-analysis of the study participants recruited in Russia.&#x0D; Results: The Russian study group included 1493 patients receiving Gla-300. At 6 months, 25.9% of the patients achieved their predefined individualized HbA1c target and 53.3% achieved their HbA1c target at month 12. Their mean ( SD) HbA1c level decreased from 9.3 0.9% at baseline to 7.6 0.7% and 7.2 0.7 at months 6 and 12. The incidence of hypoglycemia was generally low; overall, severe hypoglycemia was reported only in 0.07% and 0.13% of the patients at 6 and 12 months. The baseline average daily dose of Gla-300 was 13.2 4.9 Units; it to 23.6 9.1 and 26.0 9.8 Units at months 6 and 12.&#x0D; Conclusion: In the real world setting, initiation of insulin Gla-300 in type 2 diabetic patients who had been out of their target glucose range with oral hypoglycemic agents is associated with improved glycemic control and low risk of hypoglycemia.

Insulin Glargine 300 U/mL Therapy in Children and Adolescents with Type 1 Diabetes.

The pharmacokinetic and pharmacodynamic properties of the second-generation basal insulin glargine 300 Units/mL (Gla-300) may be of benefit in the treatment of type 1 diabetes mellitus (T1DM). Gla-300 provides a stable and sustained time-action profile, which is associated with glycaemic control and flexible dosing schedule. This review summarises the available evidence on the safety and efficacy of Gla-300 in children and adolescents with T1DM. Gla-300 is as effective as the first-generation basal insulin glargine 100 Units/mL (Gla-100), a standard of care for patients with diabetes in reducing HbA1c, and shows a lower risk of severe hypoglycaemia and hyperglycaemia in children and adolescents with T1DM. However, Gla-300 and Gla-100 are not bioequivalent and are not directly interchangeable. Real-world studies on patients aged 6–17 years are limited. To date, only one small study assessed the effectiveness and safety of Gla-300 versus Gla-100 in newly diagnosed T1DM paediatric patients, confirming the treatment safety and effectiveness of Gla-300 in clinical practice. Gla-300 is a longer-acting basal insulin alternative in the management of children (aged ≥ 6 years) and adolescents with T1DM.

Twenty Years of Insulin Gla-100: A Systematic Evaluation of Its Efficacy and Safety in Type 2 Diabetes Mellitus.

IntroductionThis systematic review aims to present the current evidence base with respect to the initiation and intensification of insulin therapy with glargine 100 U/mL (Gla-100) compared to other insulins in people with type 2 diabetes mellitus (T2DM).MethodsA systematic literature search of PubMed (MEDLINE), EMBASE, and the Cochrane Central Register of controlled clinical trials databases was performed to identify studies published up to September 30, 2020 that compared the effects of Gla-100 to that of other insulin regimens in people with T2DM. Relevant information pertaining to the predefined outcomes of interest was extracted. Glycated hemoglobin (HbA1c) change and response rates along with overall hypoglycemia incidence were the primary efficacy and safety outcomes of interest.ResultsSeventy-nine studies (63 interventional and 16 non-interventional) in which Gla-100 was either initiated in previously insulin-naïve patients (n = 57) or used in an intensified regimen (n = 22) were identified and evaluated. In insulin-naïve patients, most studies demonstrated that Gla-100 was significantly better compared with premixed insulins and similar compared with neutral protamine Hagedorn (NPH) insulin, second-generation basal insulins, co-formulations, and other first-generation basal insulins in terms of the primary efficacy parameters. Overall hypoglycemia risk with Gla-100 was significantly lower compared with NPH, premixed, coformulation, and other first-generation basal insulins and significantly higher compared with second-generation basal insulins. In studies with intensified regimens, efficacy outcomes with Gla-100 were significantly better compared with insulin detemir (IDet); similar compared with NPH, second-generation basal insulins, co-formulations; and with premixed insulins. In these studies, overall hypoglycemia risk with Gla-100 was significantly lower compared with IDet and comparable to NPH, premixed insulins, co-formulations, and second-generation basal insulins. In addition, most intensification studies also revealed a significantly lower risk of nocturnal hypoglycemia with Gla-100–based regimens versus NPH and premixed insulins and a significantly greater risk compared to second-generation basal insulins.ConclusionsThe evidence presented in this review suggests that Gla-100 is an effective option for both insulin initiation and intensification strategies used in the management of T2DM.Supplementary InformationThe online version contains supplementary material available at 10.1007/s13300-022-01284-2.

268-OR: Impact of the COVID-Pandemic on Antihyperglycemic Prescription Patterns in Canada

Background: COVID-public health measures may have impacted diabetes care through delayed care and reduced medication access. This study describes antihyperglycemic medication prescription patterns among adults with type 2 diabetes (T2D) before and during the COVID-pandemic in Canada. Methods: Using IQVIA’s longitudinal pharmacy based prescription data, antihyperglycemic prescriptions from March 1, 2018 to February 28, 2021 were analyzed among adults who had ≥1 prescription for a non-insulin antihyperglycemic drug. The number of people who: 1) had antihyperglycemic prescriptions,2) were newly started on antihyperglycemic drugs, and3) were newly diagnosed with T2D (inferred from prescriptions) were reported. Results: The number of people who had ≥1 antihyperglycemic prescription was comparable in the year of the COVID-pandemic (March 2020 to February 2021) and the year prior (March 20to February 2020) . The number of people who newly initiated a GLP-1RA, SGLT2i or second-generation basal insulin analogue decreased for the first few months of the pandemic (April to September 2020) with recovery thereafter. The number of people who were newly diagnosed with T2D decreased by 7% in the COVID-year. Conclusion: Fewer people initiated newer antihyperglycemic medications and fewer people were newly diagnosed with T2D in the first few months for the pandemic which may reflect reduced health care access. Disclosure A.Y.Cheng: Advisory Panel; Abbott, AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Dexcom, Inc., Eli Lilly and Company, HLS Theraoeutics, Insulet Corporation, Janssen Pharmaceuticals, Inc., Medtronic, Novo Nordisk, Sanofi, Board Member; Type 1 Diabetes Think Tank Network, Other Relationship; Diabetes Canada, Speaker's Bureau; Bausch Health, Canada, Merck &amp; Co., Inc. R.Goldenberg: Consultant; IQVIA Inc., Speaker's Bureau; Amgen Canada, AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Janssen Pharmaceuticals, Inc., Merck &amp; Co., Inc., Novo Nordisk Canada Inc., Sanofi. I.E.Krawchenko: Speaker's Bureau; Janssen Pharmaceuticals, Inc. R.Tytus: Other Relationship; Banty , Boehringer Ingelheim International GmbH, Canadian Health Research Company, Merck &amp; Co., Inc., Novo Nordisk, Pfizer Inc. J.Hahn: Employee; Novo Nordisk Canada Inc. A.R.Liu: Employee; Novo Nordisk A/S, Novo Nordisk Canada Inc. T.Lan: Other Relationship; Novo Nordisk Canada Inc. B.Millson: Other Relationship; Novo Nordisk Canada Inc. S.B.Harris: Consultant; Abbott, AstraZeneca, Eli Lilly and Company, Novo Nordisk, Sanofi, Other Relationship; Abbott, AstraZeneca, Bayer Inc., Dexcom, Eli Lilly and Company, HLS Therapeutics, Janssen Pharmaceuticals, Inc., Novo Nordisk, Sanofi, Research Support; Applied Therapeutics Inc., AstraZeneca, Canadian Institutes of Health Research, Juvenile Diabetes Research Foundation (JDRF) , Novo Nordisk, Sanofi, The Lawson Foundation.

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

Real-world outcomes of addition of insulin glargine 300 U/mL (Gla-300) to glucagon-like peptide-1 receptor agonist (GLP-1RA)therapy in people with type 2 diabetes: The DELIVER-G study.

To provide real-world data on the addition of basal insulin (BI) in people with type 2 diabetes mellitus (PWD2) suboptimally controlled with glucagon-like peptide-1 receptor agonist (GLP-1RA) therapy. However, real-world data on the addition of BI to GLP-1RA therapy are limited. We used a US electronic medical record data source (IBM® Explorys®) that includes approximately 4 million PWD2 to assess the real-world impact of adding the second-generation BI analogue insulin glargine 300 U/mL (Gla-300) to GLP-1RA therapy. Insulin-naïve PWD2 receiving GLP-1RAs who also received Gla-300 between March 1, 2015 and September 30, 2019 were identified; participants were required to have data for ≥12 months before, and ≥6 months after, addition of Gla-300. The mean (standard deviation [SD]) age of participants (N=271) was 57.9 (10.8) years. Baseline glycated haemoglobin (HbA1c) was 9.16% and was significantly reduced (-0.97 [SD 1.60]%; P< 0.0001) after addition of Gla-300; a significant increase in the proportion of PWD2 achieving HbA1c control was observed after addition of Gla-300 (HbA1c <7.0%: 4.80% vs. 22.14%, P< 0.0001; HbA1c <8.0%: 19.56% vs. 51.29%, P< 0.0001). The incidence of overall (8.49% vs. 9.59%; P= 0.513) and inpatient/emergency department (ED)-associated hypoglycaemia (0.37% vs. 0.74%; P= 1.000), as well as overall (0.33 vs. 0.46 per person per year [PPPY]; P= 0.170) and inpatient/ED-associated hypoglycaemia events (0.01 vs. 0.04 PPPY; P= 0.466) were similar before and after addition of Gla-300. In US real-world clinical practice, adding Gla-300 to GLP-1RA significantly improved glycaemic control without significantly increasing hypoglycaemia in PWD2. Further research into the effect of adding Gla-300 to GLP-1RA therapy is warranted.

IDF21-0686 Indirect treatment comparison of efficacy and safety of insulin glargine 300 U/mL with once-daily-insulin premix in T2DM

Background: There are no head-to-head randomized clinical trials comparing the efficacy and safety of insulin glargine 300 U/mL (Gla-300), a second-generation basal insulin analogue, with once-daily (OD) insulin premix.

IDF21-0195 Reported pregnancy outcomes with insulin glargine 300 U/mL: a post-marketing survey of pharmacovigilance data

Background: It is essential for people with pre-existing or gestational diabetes to maintain good metabolic control throughout pregnancy to prevent adverse outcomes associated with hyperglycaemia. To attain blood glucose control during pregnancy, insulin glargine and other basal insulins are treatment options. Insulin glargine 300 U/mL (Gla-300) is a second-generation basal insulin analogue that has been shown to provide similar glycaemic control with less hypoglycaemia versus the first-generation basal insulin analogue, insulin glargine 100 U/mL. However, there are currently no randomised controlled trials specifically designed to investigate the use of Gla-300 during pregnancy. Aim: The present analysis aims to examine the safety of Gla-300 use in women with diabetes during pregnancy in real-life practice, using post-marketing pharmacovigilance data. Method: Using Medical Dictionary for Regulatory Activities (MedDRA) terms, a cumulative search of Sanofi’s global pharmacovigilance database was performed to identify pregnancy outcomes during Gla-300 use, up until 9 March 2021. Results: Post-marketing searches identified 246 cases for analysis (66 solicited, 180 unsolicited) (Table) from 44 countries. Cumulative exposure to Gla-300 was 7.9 million person-years. Reporting rates for adverse events of specific interest were 31.1/1,000,000 person-years. Congenital, familial, and genetic anomalies were rare with Gla-300 (5, 2.0%: one cardiac, one genito-urinary, one musculoskeletal and connective tissues, one respiratory, and one gastrointestinal tract disorder); this is consistent with the rate of birth defects reported for the general population, which is ∼3–5% of all live births. Spontaneous abortions were also rare (7, 2.8%), consistent with miscarriage rates observed in the general population (≥∼10%). Table.Tabled 1MedDRA search termNumber of events (%)a,bReporting ratec.d,e (events per 1,000,000 person-years)Total number of pregnancy exposures (including 1 exposure via father)246 (N/A)31.1Abortion (induced)0 (0.0)0.00Abortion (spontaneous)7 (2.8)0.89Abortion (not specified as induced or spontaneous)4 (1.6)0.51Anembryonic gestation1 (0.4)0.13Congenital, familial, and genetic disorders5 (2.0)0.63Ectopic pregnancy0 (0.0)0.00Exposures via breast milk8 (3.3)1.01Premature birth7 (2.8)0.89Postmature birth0 (0.0)0.00Stillbirth1 (0.4)0.13Live birth/unknown or missing outcome237 (96.3)30.00 Open table in a new tab aSome cases may be counted more than once owing to multiple events reported in one case; bPercentage calculation is based on total number of pregnancy/lactation related cases (246); cThe reporting rate is based on cumulative exposure as there are no data by gender; dData collected from IMS Health; eCumulative exposure to Gla-300 (7.9 million person-years) based on data collected up to 26 January 2021. MedDRA, Medical Dictionary for Regulatory Activities; N/A, not applicable Discussion: Rates of spontaneous abortions and congenital anomalies were low for Gla-300 and consistent with rates in the general population. Use of Gla-300 during pregnancy was not associated with specific adverse events/congenital abnormalities. These results indicate no safety issues with use of Gla-300 during pregnancy.