Second-generation Basal Insulin Research Articles

Real-world persistence, adherence, health care resource utilization, and costs in people with type 2 diabetes switching from a first-generation basal insulin to a second-generation (insulin glargine 300 U/mL) vs an alternative first-generation basal insulin.

BACKGROUND: People with type 2 diabetes (T2D) who change their basal insulin (BI) may have variable persistence with therapy. Compared with first-generation (long-acting) BI analogs (insulin glargine 100U/mL [Gla-100]; insulin detemir [IDet]), second-generation (longer-acting) BI analogs (insulin glargine 300U/mL [Gla-300]; insulin degludec) have similar glycated hemoglobin (HbA1c) attainment and lowered hypoglycemia risk, which could impact treatment persistence. OBJECTIVE: To compare persistence, adherence, health care resource utilization (HRU), and costs for individuals switching from neutral protamine Hagedorn insulin or a first-generation BI analog with either the second-generation BI, Gla-300, or an alternative first-generation BI analog (Gla-100 or IDet). METHODS: We used Optum Clinformatics claims data from adults (aged ≥ 18 years) with T2D who had received BI (neutral protamine Hagedorn, Gla-100, IDet) in the 6-month baseline period, and switched to either Gla-300 or an alternative first-generation BI (Gla-100 or IDet; treatment switch = index date) between April 1, 2015, and August 31, 2019. Participants were followed for 12 months, until plan disenrollment, or until death, whichever occurred first. Cohorts were propensity score matched (PSM) on baseline characteristics. The primary outcome was the proportion who were persistent with therapy at 12 months. Secondary outcomes were adherence (proportion of days covered); change in HbA1c; and all-cause, diabetes-related, and hypoglycemia-related HRU and costs. RESULTS: PSM generated 3,077 participants/group (mean age: 68 years, 52% female). Cohorts were well balanced except for hospitalization, which was adjusted in models as a covariate. During the 12-month follow-up period, participants who received Gla-300 vs first-generation BI had greater persistence with (45.5% vs 42.1%; adjusted P = 0.0001), and adherence to (42.8% vs 38.2%; adjusted P = 0.0006), BI therapy and a statistically larger reduction in HbA1c at 12 months (-0.65% vs -0.45%; adjusted P = 0.0040). The proportion of participants achieving HbA1c less than 8% (47.2% vs 40.9%; P < 0.0001), but not less than 7% (21.2% vs 20.8%), was significantly higher for Gla-300 vs first-generation BI. All-cause (45.3 vs 65.9 per 100 patient-years [P100PY]) and diabetes-related (21.5 vs 29.1 P100PY), but not hypoglycemia-related, hospitalizations (1.0 vs 1.5 P100PY) were significantly (P < 0.0001) lower for Gla-300 vs first-generation BI. Similarly, all-cause (111.9 vs 148.8 P100PY), diabetes-related (54.8 vs 74.2 P100PY), and hypoglycemia-related (2.9 vs 5.7 P100PY) emergency department (ED) visits were significantly lower for Gla-300 (all P < 0.0001). Costs for all-cause hospitalizations and hypoglycemia-related ED visits were significantly lower for Gla-300 vs first-generation BI. Although pharmacy costs were significantly higher for Gla-300 vs first-generation BI, all-cause total health care costs were not significantly different: $41,255 vs $45,316 per person per year, respectively. CONCLUSIONS: In this claims-based analysis of people with T2D receiving BI, switching to Gla-300 was associated with significantly better persistence, adherence, and HbA1c reduction compared with switching to an alternative first-generation BI analog. All-cause HRU was significantly lower; despite significantly higher pharmacy costs, total health care costs were similar. DISCLOSURES: This study was funded by Sanofi US. Medical writing support was provided by Helen Jones, PhD, CMPP, of Evidence Scientific Solutions and funded by Sanofi US. Dr Wright is on the speakers' bureau and sits on the advisory boards for Abbot Diabetes, Bayer, Boehringer Ingelheim, Eli Lilly, and Sanofi; sits on the advisory board for Medtronic; and is a consultant for Abbot Diabetes, Bayer, Boehringer Ingelheim, and Eli Lilly. Dr Malone is on advisory boards for Novartis and Avalere and consults for Pear Therapeutics, Sarepta, and Strategic Therapeutics. Dr Trujillo sits on advisory boards for Novo Nordisk and Sanofi. Drs Gill, Zhou, and Preblick and Mr Li are employees and stockholders of Sanofi. Mr Huse is an employee of Evidera and a contractor for Sanofi. Dr Reid is a speaker and consultant for Novo Nordisk and Sanofi-Aventis and is a consultant for AstraZeneca and Intarcia.

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.

Basal Insulin Degludec and Glycemic Control Compared to Aspart Via Insulin Pump in Type 1 Diabetes (BIGLEAP): A Single-Center, Open-Label, Randomized, Crossover Trial

ObjectiveWe compared the efficacy of the second-generation basal insulin degludec (IDeg) to that of insulin aspart via pump using continuous glucose monitoring in patients with well-controlled type 1 diabetes. MethodsIn this 40-week, single-center, randomized, crossover-controlled trial, adults with well-controlled type 1 diabetes (hemoglobin A1C of <7.5% [<58 mmol/mol]) (N = 52) who were using an insulin pump and continuous glucose monitoring were randomized to 1 of 2 treatments for a 20-week period: a single daily injection of IDeg with bolus aspart via pump or a continuous subcutaneous insulin infusion (CSII) with aspart, followed by crossover to the other treatment. The primary endpoint was time in range (70-180 mg/dL) during the final 2 weeks of each treatment period. ResultsFifty-two patients were randomized and completed both treatment periods. The time in range for IDeg and CSII was 71.5% and 70.9%, respectively (P = .553). The time in level 1 hypoglycemia for the 24-hour period with IDeg and CSII was 2.19% and 1.75%, respectively (P = .065). The time in level 2 hypoglycemia for the 24-hour period with IDeg and CSII was 0.355% and 0.271%, respectively (P = .212), and the nocturnal period was 0.330% and 0.381%, respectively (P = .639). The mean standard deviation of blood glucose levels for the 24-hour period for IDeg and CSII was 52.4 mg/dL and 51.0 mg/dL, respectively (P = .294). The final hemoglobin A1C level for each treatment was 7.04% (53 mmol/mol) with IDeg, and 6.95% (52 mmol/mol) with CSII (P = .288). Adverse events were similar between treatments. ConclusionWe observed similar glycemic control between IDeg and insulin aspart via CSII for basal insulin coverage in patients with well-controlled type 1 diabetes.

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

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

Basal insulin analogues in people with diabetes and chronic kidney disease.

Diabetic kidney disease is the leading cause of chronic kidney disease (CKD) and end-stage kidney disease (ESKD) worldwide. ESKD has a high prevalence in patients with diabetes mellitus (DM). CKD increases the chances of hypoglycaemia by different mechanisms, causes insulin resistance and a decrease in insulin metabolism. Both the "Kidney Disease: Improving Global Outcomes" (KDIGO) and "American Diabetes Association" (ADA) guidelines recommend the use of insulin as part of treatment, but the type of basal insulin is not specified. We reviewed the literature to determine whether first- and second-generation basal insulins are effective and safe in CKD patients. We reviewed specific pivotal studies conducted by pharmaceutical laboratories, as well as independent studies. Basal insulins are safe and effective in patients with CKD and diabetes mellitus but we do not have specific studies. Given that CKD is one of the main complications of type 2 DM, and insulin specific treatment in the final stages, the absence of studies is striking. Real-life data are also important since trials such as pivotal studies do not fully represent actual patients. Treatment should be individualized until we have specific trials in this type of population.

Efficacy and safety among second-generation and other basal insulins in adult patients with type 1 diabetes: a systematic review and network meta-analysis.

We aimedto assess the comparative efficacy and safety of second-generation basal insulins (glargine U300 and degludec U100) vs. neutral protamine Hagedorn (NPH) and first-generation basal insulins (glargine U100 and detemir) in type 1 diabetes (T1D) adults.PubMed, the Cochrane Library, ClinicalTrials.gov, and Google Scholar (until January 2021) were systematically searched. Randomized controlled trials (RCTs) with ≥ 12weeks of follow-up comparing efficacy (HbA1c) or safety (hypoglycemia and weight gain) between second-generation basal insulins vs. other basal insulins in T1D adults were included. Bayesian network meta-analyses were used to estimate risk ratio, hazard ratio, and mean difference. Grading of Recommendations, Assessment, Development and Evaluation (GRADE) was used to appraise evidence certainty.Eighteen RCTs (≥ 24weeks of follow-up) involving 7283 randomized participants were included for main analysis. Moderate to high certainty evidence suggested that second-generation basal insulins showed equivalent HbA1c reduction compared with NPH and first-generation basal insulins. Compared with second-generation basal insulins, low to high certainty evidence suggested that NPH was associated with a higher risk of patients experiencing severe hypoglycemia; NPH and first-generation basal insulins were associated with a higher rate of nocturnal confirmed hypoglycemic events. For the weight gain, glargine U300 was comparable to detemir (low certainty), but degludec U100 was greater than detemir (moderate certainty).In conclusion, second-generation basal insulins maintained equivalent efficacy of glycemic control (moderate to high certainty), with differences in safety (low to high certainty) compared with NPH and first-generation basal insulins during ≥ 24weeks of follow-upin T1D adults.

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 …

103-LB: Real-World Persistence, Adherence, Health Care Resource Utilization, and Costs in People with Type 2 Diabetes (T2D) Switching from Basal Insulin (BI) to Second-Generation BI (Insulin Glargine 300 U/mL [Gla-300]) vs. First-Generation BI (Insulin Glargine 1

This retrospective observational study using the Optum Clinformatics claims database included data from adults (≥18 y) with T2D who had received prior basal insulin (BI) (NPH, Gla-100, IDet) in the 6-month baseline period, and switched to either the second-generation (2nd-gen) BI, Gla-300 or a first-generation (1st-gen) BI (Gla-100, IDet) (treatment switch=index date) between April 1, 2015 and August 31, 2019. Participants were followed from index date for 12 months or plan disenrollment or death. Cohorts were propensity score matched (PSM) on baseline demographic/clinical characteristics. Outcomes were persistence (days on treatment without discontinuation), adherence (proportion days covered), healthcare resource utilization and costs. After PSM (n=3077/cohort; mean age 68 y, 52% female), cohorts were well balanced except for 1 variable (hospitalization) with standardized difference &amp;gt;0.1, which was adjusted in models as a covariate. During the 12-month follow-up period, higher proportions of participants who received Gla-300 vs. 1st-gen BI were persistent (45.5 vs. 42.1%; adjusted p=.0001) and adherent (42.8 vs. 38.2%; adjusted p=.0006). All-cause healthcare resource utilization was lower for Gla-300 vs. 1st-gen BI (emergency room visits 111.9 vs. 148.8 events per 100 patient-years [PY]; inpatient hospitalizations 45.3 vs. 65.9 events per 100 PY; adjusted p&amp;lt;.0001). Total healthcare costs were numerically lower for Gla-300 vs. 1st-gen BI ($41,255 vs. $45,316 per PY). Switching to Gla-300 was associated with significantly better persistence, adherence, and—despite these associated costs—lower all-cause healthcare resource utilization vs. switching to a 1st-gen BI, in people with T2D previously treated with BI therapy. This is the first study to assess these outcomes in tandem. Disclosure E. Wright: Advisory Panel; Self; Abbott Diabetes, Bayer Healthcare Pharmaceuticals Inc., Boehringer Ingelheim International GmbH, Sanofi, Consultant; Self; Abbott Diabetes, Boehringer Ingelheim Pharmaceuticals, Inc., Other Relationship; Self; American Diabetes Association, Speaker’s Bureau; Self; Bayer Healthcare Pharmaceuticals Inc., Sanofi. J. Gill: Employee; Self; Sanofi US, Other Relationship; Self; American Diabetes Association, Stock/Shareholder; Self; Sanofi US. S. Huse: Consultant; Self; Sanofi US. X. Li: Employee; Self; Sanofi US. T. Reid: Other Relationship; Self; Sanofi US. F. L. Zhou: Employee; Self; Sanofi, Stock/Shareholder; Self; Sanofi. Funding Sanofi US

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.

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

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

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.

Clinical Outcomes of Switching to Insulin Glargine 300 U/ml from Other Basal Insulins in People with Type 2 Diabetes in Italy: A Real-World Study.

IntroductionPrimary aim was to provide real-world evidence of the outcomes after the switch to glargine 300 U/ml (Gla-300) from other basal insulins (first or second generation) in Italy.MethodsMulticenter, observational, retrospective study based on electronic medical records.ResultsOverall, 953 T2DM insulin ± OAD treated people switched to Gla-300 or Gla-100 from January 2015 to July 2018. Three clinically relevant cohorts were identified: patients switching to Gla-300 from first-generation basal insulin (cohort 1), patients switching to Gla-300 from degludec-100 (Deg-100) (cohort 2), and those switching to Gla-100 from any basal insulin (cohort 3). The three cohorts differed in terms of age, diabetes duration, and metabolic control. HbA1c changes after 6 months from the switch were − 0.27% (95% CI − 0.38; − 0.16), − 0.06% (95% CI − 0.31; 0.19), and − 0.30% (95% CI − 0.51; − 0.09) in the three cohorts, respectively. FPG significantly decreased in cohort 1 (− 14.07 mg/dl, 95% CI − 20.25; − 7.89), while body weight significantly decreased in cohort 2 (− 1.47 kg, 95% CI − 2.55; − 0.39). Doses of insulin marginally changed during the follow-up (+ 0.89 U in basal insulin daily dose in cohort 1 and + 2.07 U in short-acting insulin daily dose in cohort 2).ConclusionsSwitching to Gla-300 from first-generation basal insulin in the real world is associated with improvements in metabolic control despite a suboptimal titration of both basal and short-acting insulins. Inertia in insulin titration documented in the Gla-100 cohort is also observed with the second-generation basal insulin. The switch to Gla-300 from Deg-100 was associated with a decrease in body weight of − 1.47 kg despite a slight increase in short-acting insulin daily doses of about + 2 U.

Persistence with Basal Insulin and Frequency of Hypoglycemia Requiring Hospitalization in Patients with Type 2 Diabetes.

IntroductionA second-generation basal insulin analogue insulin glargine 300 U/mL (Gla-300) has been marketed in France since June 2016. This real-world study was designed to assess persistence with Gla-300 and the prevalence of related hypoglycemia requiring hospitalization as compared to first-generation basal insulins, in patients with type 2 diabetes mellitus (T2DM). MethodsA retrospective study was conducted using data in the large French comprehensive national healthcare system claims databases. Patients with T2DM newly treated with insulin in 2016 and 2017 (2-year period) were included. Three basal insulins [Gla-300, glargine 100 U/mL (Gla-100; both branded and biosimilar) and insulin detemir (IDet)] were compared for (1) persistence until treatment discontinuation using adjusted Cox models and (2) hypoglycemia requiring hospitalization over the period of insulin exposure.ResultsDuring the 2-year study period, in France, 181,263 patients initiated basal insulin therapy (in a basal scheme or a more complex insulin scheme), of whom 74% initiated Gla-100, 14.2% initiated IDet and 11.8% initiated Gla-300. Patient characteristics varied according to the insulin regimen in terms of age, gender, social coverage, insulin scheme, and Charlson Comorbidity Index. Overall, 72% of patients were still treated with any basal insulin after 1 year (75% in basal scheme). In all insulin treatment regimens, patients were less likely to discontinue Gla-300 as compared to Gla-100 [adjusted odds ratio (OR) 0.39, 95% confidence interval (CI) 0.37–0.41], with similar results when only the basal scheme was considered (adjusted OR 0.38, 95% CI 0.35–0.40). Persistence with IDet was similar to that with Gla-100. Patients treated with Gla-100 had higher crude hospitalization rates for hypoglycemia than those receiving Gla-300 (1.4 for 100 patients-years; OR 0.67, 95% CI 0.55–0.81); however, this difference was not statistically significant after adjustment for patient characteristics. Emergency Room (ER) visits were less frequent in patients treated with Gla-300 versus Gla-100 with or without adjustment for patient characteristics (p < 0.0001).ConclusionReal-world persistence for basal insulin therapy in patients with T2DM was significantly better in those on Gla-300 compared with those on Gla-100 and IDet. A trend to a lower frequency of hospitalization for hypoglycemia and ER visits, whatever the cause, was also observed in patients on Gla-300.

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.

1028-P: Real-World Effectiveness and Safety of Insulin Glargine 300 U/mL (gla-300) in Insulin-Naïve Patients with Type 2 Diabetes (T2DM): Interim Analysis of the ATOS Study

ATOS is a prospective, 12-month, observational study assessing real-world effectiveness of the second-generation basal insulin analog Gla-300 in emerging markets. Insulin-naïve adults (≥18 years) with T2DM, HbA1c &amp;gt;7-≤11 % and previously treated with ≥1 oral antihyperglycemic drug were recruited in 18 countries. An interim analysis was undertaken when ≥50% of participants had 6-months’ follow-up data (cut-off July 1, 2019); this included 4527 eligible patients (Eastern Europe: 1748; Egypt: 214; India: 1269; Latin America and Caribbean: 317; Western Asia: 882; Southeast Asia: 46; Taiwan: 51). Mean (SD) age was 57.2 (10.8) years, BMI was 29.4 (5.3) kg/m2, and duration of diabetes was 10.2 (6.2) years; 48.4% were male. Physician-set individualized HbA1c (%) goals at baseline were &amp;lt;7: 13.7%; 7-&amp;lt;7.5: 70.3%; 7.5-&amp;lt;8: 11.9%; ≥8: 4.2%. The proportion of evaluable patients achieving HbA1c goal at Month 6 (primary outcome) was 25.1% (95% CI: 23.6 to 26.6); HbA1c decreases are shown in Table. Hypoglycemia incidence was low (&amp;lt;2%). Treatment-emergent adverse events (TEAEs) were reported in 230 (5.0%) patients, with 47 (1.0%) serious TEAEs (included population). ATOS showed high baseline HbA1c, suggesting delayed insulin initiation; introduction of Gla-300 led to marked improvements in HbA1c with a good safety profile in a real-world setting. Disclosure G.R. Galstyan: None. A. Bhansali: None. H. Vargas-Uricoechea: Speaker’s Bureau; Self; Sanofi-Aventis. A. Tirosh: Advisory Panel; Self; Novo Nordisk Inc., Sanofi. G. Sun: None. M. Naqvi: Employee; Self; Sanofi. V. Pilorget: Employee; Self; Sanofi. M. Coudert: Employee; Self; Roche Pharma, Sanofi-Aventis. D. Cherkasov: None. N. Khan: None. Funding Sanofi (ATOS/NCT03703869)

1035-P: Real-World Safety and Effectiveness of Insulin Glargine 300 U/mL (Gla-300) in People with Type 2 Diabetes (T2DM) Who Fast during Ramadan: Regional Analysis of the ORION Study

ORION, a prospective observational study, evaluated the safety and effectiveness of the second-generation basal insulin analog Gla-300 in people who fast during Ramadan. Adults (≥18 years) with T2DM who intended to fast for ≥15 days during Ramadan, had taken Gla-300 for ≥8 weeks before inclusion and intended to continue during Ramadan were enrolled in 11 countries (grouped by region; Table). Mean (SD) number of fasting days was 30.1 (3.2). Mean diabetes duration ranged from 7.9 to 13.5 years and ≥77.5% had moderate/low risk associated with fasting (investigator-assessed). Proportions of people with ≥1 severe and/or symptomatic documented hypoglycemia event were low for the overall population and in Groups 1-3; 1 severe hypoglycemia event was reported in pre-Ramadan. Glycemic control improved pre- to post-Ramadan in Groups 1-3 and Gla-300 dose adjustments were minimal. In Canada, 24% of people had ≥1 severe and/or symptomatic documented hypoglycemia event in Ramadan; there was no change in glycemic control, but pre-Ramadan HbA1c target achievement was high (30.4%). In this real-world study, people with T2DM who received Gla-300 and fasted for Ramadan generally had low incidence of hypoglycemia, with no severe events in Ramadan, and slightly improved glycemic control; results from Canada varied, possibly due to longer fasting hours. Disclosure M. Hassanein: Advisory Panel; Self; Novo Nordisk A/S. Speaker’s Bureau; Self; Lilly Diabetes, Merck Sharp &amp; Dohme Corp., Novo Nordisk A/S, Sanofi. M.A. Buyukbese: Consultant; Self; Sanofi. R. Malek: None. V. Pilorget: Employee; Self; Sanofi. M. Naqvi: Employee; Self; Sanofi. B. Berthou: None. I. Shaltout: Advisory Panel; Self; Sanofi, Novartis, MSD, Astra Zeneca, Novo Nordisk, Lilly, Servier and Abbott. Speaker’s Bureau; Self; Sanofi, Novartis, MSD, Astra Zeneca, Novo Nordisk, Lilly, Servier and Abbott. R. Sahay: Advisory Panel; Self; Boehringer Ingelheim, Dr. Reddy’s Laboratories, Eli Lilly and Company, Sanofi. Speaker’s Bureau; Self; Boehringer Ingelheim, Eli Lilly and Company, Novo Nordisk A/S, Sanofi. Funding Sanofi; World Health Organization (CTRI/2019/02/017636)

SUN-LB126 Real-World Safety and Effectiveness of Insulin Glargine 300 U/ML (Gla-300) in People With Type 2 Diabetes Who Fast During Ramadan

ORION was a prospective, observational study evaluating the safety and effectiveness of the second-generation basal insulin analog Gla-300 in people with type 2 diabetes (T2DM) who fast during Ramadan. Adults with T2DM who intended to fast for ≥15 days during Ramadan, had taken Gla-300 for ≥8 weeks prior to inclusion, and intended to continue its use during Ramadan were enrolled in 11 countries. During Ramadan, Gla-300 treatment was adjusted as per routine practice by the treating physician. Overall, the majority of people (402 [85%]) fasted for the entire Ramadan period and 10.8% fasted for ≥25 days but with at least one missed day. Mean (SD) age was 54.4 (11.0) years, 51.7% were male, BMI was 29.7 (5.3) kg/m2, and duration of diabetes was 10.7 (7.0) years. Risks of diabetes-related complications associated with fasting were assessed by physicians according to IDF-DAR fasting risk category; risk was low/moderate in 82.8%, high in 14.3%, and very high in 2.9% of people. The proportion of people with ≥1 severe and/or documented symptomatic (SMPG ≤70 mg/dL) hypoglycemia event was low (2.2% [event rate: 0.021 per participant-month (PPM)] in pre-Ramadan, 2.6% [0.039 PPM] in Ramadan and 0.2% in post-Ramadan [0.003 PPM]). Overall, 0.8% (0.005 PPM) of participants experienced severe and/or documented symptomatic hypoglycemia at SMPG <54 mg/dL, and only during pre-Ramadan. No participants had severe hypoglycemia during Ramadan or post-Ramadan; 1 participant had severe hypoglycemia pre-Ramadan. Most of those who experienced symptomatic hypoglycemia during Ramadan did so during fasting hours (11/13 people). Reductions were shown pre- to post-Ramadan for mean (SD) HbA1c (8.10 % [1.29] pre-Ramadan to 7.64 % [1.05] post-Ramadan; change of −0.44 % [0.97]), FPG (144.3 [45.8] mg/dL pre-Ramadan to 128.5 [37.8] mg/dL post-Ramadan; change of −13.5 [44.1] mg/dL), and fasting SMPG (130.7 [32.9] mg/dL pre-Ramadan to 126.8 [28.5] mg/dL post-Ramadan; change of −3.3 [26.6] mg/dL). Mean Gla-300 dose was reduced slightly between pre-Ramadan and Ramadan (25.6 [11.9] U/0.32 [0.14] U/kg pre-Ramadan to 24.4 [11.5] U/0.30 [0.13] U/kg in Ramadan) and returned to 26.0 (12.2) U/0.32 (0.14) U/kg in the post-Ramadan period. AE incidence was low (5.5%); 3 (0.6%) participants had an AE of hyperglycemia, 2 (0.4%) during Ramadan. In this study, performed in a real-world setting, incidence of hypoglycemia was low in people with T2DM treated with Gla-300 who fasted for Ramadan, with no incidence of severe hypoglycemia during the Ramadan period; HbA1c, FPG and fasting SMPG reductions were also observed. Supported By: Sanofi

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.