Glargine U100 Research Articles

15-LB: Diabetes Duration Did Not Moderate the Reduction in Severe Hypoglycemia Seen with Degludec vs. Glargine U100 in DEVOTE

Hypoglycemia is associated with significant morbidity in type 2 diabetes (T2D). Progression of T2D leads to declining counterregulatory responses and heightened hypoglycemia risk. In this secondary analysis of data from DEVOTE, a CVOT with 7637 patients with T2D at high risk of cardiovascular events, we investigated diabetes duration as a moderator of severe hypoglycemia (SH) with use of glargine U100 (IGlar U100) versus insulin degludec. Patients in DEVOTE were categorized by diabetes duration in years: <10, 10-15, 15-20 and ≥20. Prevalence of SH was examined by treatment arm (Table) using a negative binomial model with log-observation time as an offset term, and diabetes duration categories as moderators. Both proportion of patients with SH events and rate of SH increased with progression of disease in both arms. Degludec preserved its relative benefit over IGlar U100 for SH across diabetes duration groups, even in less progressed disease groups, i.e., an observed 52% relative risk reduction for degludec vs. IGlar U100 for patients within 10 years of disease onset (95% CI: 0.29; 0.81). There was no significant difference in treatment ratios across categories (p-value for interaction=0.50). Similar findings were confirmed in the SWITCH 2 trial (data not shown). Thus, diabetes duration did not moderate the relative reduction in rate of SH for degludec vs. IGlar U100 in DEVOTE. Disclosure A. Alexopoulos: None. K. Kvist: Employee; Self; Novo Nordisk A/S. Stock/Shareholder; Self; Novo Nordisk A/S. E. Hachmann-Nielsen: Employee; Self; Novo Nordisk A/S. J.B. Buse: Consultant; Self; Neurimmune AG. Research Support; Self; AstraZeneca, National Center for Advancing Translational Sciences, National Institute of Diabetes and Digestive and Kidney Diseases, Novo Nordisk A/S, Sanofi, vTv Therapeutics. Stock/Shareholder; Self; Mellitus Health, PhaseBio Pharmaceuticals, Inc., Stability Health. Other Relationship; Self; ADOCIA, AstraZeneca, Dance Biopharm Holdings Inc., Eli Lilly and Company, MannKind Corporation, NovaTarg, Novo Nordisk A/S, Senseonics, vTv Therapeutics, Zafgen, Inc. Funding Novo Nordisk A/S

1088-P: A PK/PD and Metabolic Head-to-Head Comparison of Clinical Doses of Insulin Glargine U300 and Degludec in Type 1 Diabetes

Aim: to compare head-to-head pharmacokinetics (PK), pharmacodynamics (PD), glucose fluxes and lipid metabolism of clinical doses of insulin glargine U300 (Gla-300) and degludec U100 (IDeg) in real life in T1DM. Methods: 22 subjects [(11M, age 44±12, T1DM for 26±12 years, BMI 22.5±3.2 kg/m2, A1C 7.1±0.6% (53.4±7.1 mmol/mol)] on Gla-100, naïve to Gla-300 and IDeg, were studied (24h euglycemic clamp) with individual doses of Gla-300 and IDeg (dosing at 20.0h) after 3 months of optimal titration of basal-bolus insulin (random crossover). Results (at present in 14 of the 22 subjects, PD only, data in progress): preclamp A1C was similar with Gla-300 vs. IDeg. Individual basal insulin dose was greater with Gla-300 vs. IDeg (0.35±0.09 vs. 0.27±0.06 U/kg, p<0.01). Average PG (0-24h) was euglycemic on both occasions (p=NS). Area under curve of glucose infused [AUC-GIR(0-24h)] was equivalent for the two insulins (ratio 1.03, 90% C.I. 0.9, 1.22) (Figure). Within-day PD variability tended to be lower with Gla-300 vs. IDegl (CV 51% vs. 59%, p<0.051). Conclusions. In T1DM, PD of clinical doses of Gla-300 are equivalent to IDeg with a trend for lower within-day variability. Disclosure P. Lucidi: Other Relationship; Self; Abbott, Novo Nordisk A/S. F. Porcellati: Board Member; Self; AstraZeneca, Eli Lilly and Company, Sanofi. Consultant; Self; Medtronic. P. Candeloro: None. P. Cioli: None. C. Pascucci: None. G.B. Bolli: Advisory Panel; Self; Sanofi. Research Support; Self; A. Menarini Diagnostics, Medtronic. C. Fanelli: Advisory Panel; Self; Sanofi. Other Relationship; Self; Menarini Group.

1132-P: Real-World Clinical Use of iGlarLixi in a Large U.S. Electronic Medical Records Database

iGlarLixi, a fixed-ratio combination of insulin glargine U100 (iGlar-100) and the GLP-1 RA lixisenatide, has been available in the U.S. for clinical use in patients (pts) with T2D since 01/2017. This analysis provides baseline characteristics of iGlarLixi pts and prescribers in a real-world setting from a U.S. electronic medical records database. Pts initiating iGlarLixi from 01/2017 were reviewed using the U.S. Optum Humedica database, which includes data from approximately 85 million pt lives (insured and uninsured). Pts with at least 6 months’ data prior to iGlarLixi initiation (07/2016) were included. Baseline characteristics and clinical variables using ICD-9-CM/ICD-10-CM and prescription codes were extracted. Among 1075 total pts initiating iGlarLixi, mean age was 56.5 years (SD 10.6, range 22-89); highest number of pts (41%) were 55-64 years; 53% were female. If noted, race was 76% Caucasian, 16% African American, 1% Asian, and 8% Other/Unknown; 6% were of Hispanic ethnicity. Mean HbA1c was 9.1% (SD 2.0, median 8.8); distribution: ≥7% (80%), ≥8% (60%), and ≥9% (41%). Mean BMI (kg/m2) was 36.1 (SD 6.9, median 35.4); BMI was ≥30 for 50% and 30-<40 for 35%. Mean eGFR (mL/min/1.73 m2) was 86 (SD 26.8); of pts with known eGFR, 84% had >60. Mean Diabetes Complications Severity Index (DCSI) score was 2.4 (SD 1.7); 35% had DCSI ≥3. Previous basal insulin (BI) therapy (± OADs) was used by 41%; 14% were on GLP-1 RAs (± OADs); 15% were on BI + GLP-1 RA free combination (± OADs); 15% were on at least one OAD, without BI or GLP-1 RA. OADs (≥1) were used by 72% of pts; 38% were on ≥2 OADs. The highest number of pts were from the Midwest (61%), followed by the South (27%). Over 60% of prescribers were mid-level/family practice/internal medicine; 15% were endocrinologists. In conclusion, iGlarLixi is used for pts with a wide range of baseline demographic and clinical characteristics in widespread U.S. geographic regions. The largest use was noted in pts with high HbA1c and obesity, and most pts had previous therapies of BI or GLP-1 RAs and OADs. Disclosure J.P. Frias: Advisory Panel; Self; Becton, Dickinson and Company, Eli Lilly and Company, Gilead Sciences, Inc., Sanofi. Consultant; Self; Echosens, Genentech, Inc., Johnson & 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 & 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 & Co., Inc., Sanofi. A.H. Boss: Employee; Self; Sanofi. Stock/Shareholder; Self; Novo Nordisk A/S, Sanofi. R. Lubwama: Employee; Self; Merck & Co., Inc., Sanofi. A. Shaunik: Employee; Self; Sanofi. Funding Sanofi

Characteristics of Patients with Type-1 or Type-2 Diabetes Receiving Insulin Glargine U300: An Analysis of 7268 Patients Based on the DPV and DIVE Registries.

Insulin glargine 300 U/ml (U300) was registered based on the EDITION clinical trial program. The aim of this database analysis was to describe the profile of adult U300 recipients with type-1 (T1DM) or type-2 diabetes (T2DM). The analysis was based on data from the German DIVE/DPV registries. Patients were sampled in May (DIVE) and in March 2018 (DPV) and divided into those who commenced U300 within the 1st year (early adopters) or 2nd year (late adopters). Patients were further compared to patients receiving U100 during the same time period. Among 581,519 adult patients contained in the databases, 7268 with either T1 or T2DM received U300 and 22,050 U100. Baseline characteristics of U300 and U100 recipients did not differ substantially in both types of diabetes. Patients with T2DM had many risk factors and comorbidities. The median HbA1c (both T1DM and T2DM, 8.1% for U300 and 7.9 and 8.3% for U100) and fasting blood glucose values were similar at baseline. Severe hypoglycemia was less prevalent in T2DM and among recipients of U300 (3.1 vs. 3.9%), whereas in T1DM the rate was higher (10.6 vs. 10.1%). There were minor, but clinically probably irrelevant, differences in age and BMI for T1DM and T2DM between the first and second years. Patients with T2DM being initiated in the second year had a higher HbA1c value (8.6 vs. 8.3%) than those initiated during the first year. Patients in clinical practice showed substantially higher HbA1c values in both T1DM and T2DM, and doses used were lower than those reported from the EDITION trial program. U300 patients had a longer diabetes duration (T1 and T2DM), a higher BMI and received higher basal insulin doses (T1 and T2DM) compared to U100. While HbA1c was comparable, the rate of severe hypoglycemia under U300 was reduced in T2DM but not T1DM with or without adjustment for differences in baseline characteristics in T2DM. The data confirm the clinical profile documented for U300 in the EDITION studies during the first years of its registration. In an unselected patient population, there was a lesser rate of severe hypoglycemia but at a comparable HbA1c. German Centre for Diabetes Research (DZD) (01GI1106), the European Foundation for the Study of Diabetes (EFSD) and the German Diabetes Society (DDG). The DIVE registry (organized as Diabetes Agenda 2010 GmbH, Berlin, Germany) received funding from Sanofi, AstraZeneca, Bayer, and Abbott and was conducted under the auspices of diabetesDE.

Patient-reported outcomes from a randomized, crossover trial comparing a pen injector with insulin degludec versus a pen injector with insulin glargine U100 in patients with type 2 diabetes

Objective: Type 2 diabetes (T2D) is associated with insulin resistance and deteriorated glycemic control that can be restored with insulin injections. Choice of insulin pen injector may affect complexity, adherence, efficacy of treatment and health-related quality of life. We describe detailed patient-reported outcomes (PROs) on treatment impact and preference comparing insulin degludec (degludec) using FlexTouch1 versus insulin glargine U100 (glargine U100) with SoloStar2 pen injector.Methods: In this randomized, multicenter (USA), open-label, crossover, treat-to-target study (NCT01570751), patients with T2D using high-dose insulin (≥81 U/day from vials) were randomized (n = 145) 1:1 to 16 weeks of degludec U200 (3 mL FlexTouch) followed by 16 weeks of glargine U100 (3 mL SoloStar) or vice versa. PRO questionnaires assessed treatment impact and patient preference of pen injectors.Results: Significantly more patients (p < .01) considered FlexTouch “extremely easy” for learning (62.5 vs. 43.0%), maintaining (63.2 vs. 42.2%) and adjusting the dose (63.2 vs. 44.4%), and significantly more were “very” or “extremely confident” in using the device (60.3 vs. 36.3%) and in its accuracy (50.7 vs. 30.4%) versus SoloStar. Significantly more were “not at all bothered” by device discomfort (74.3 vs. 54.1%), whereas device size (83.8 vs. 80.0%) or public use (69.9 vs. 60.7%) were numerically in favor of FlexTouch. Significantly more patients preferred degludec treatment with FlexTouch (59 vs. 22%), preferred to continue (67 vs. 15%) and recommend (67 vs. 14%) use of FlexTouch compared with SoloStar with glargine U100.Conclusions: In this randomized, crossover trial, lower treatment impact and higher patient preference were reported for FlexTouch versus SoloStar pen injectors.

Lower rates of hypoglycaemia in older individuals with type 2 diabetes using insulin degludec versus insulin glargine U100: Results from SWITCH 2.

AimThis study aimed to investigate the safety of insulin degludec (degludec) in relation to age and risk of hypoglycaemia post hoc in individuals with type 2 diabetes (T2D) (SWITCH 2 trial).MethodsIn this crossover study, individuals with T2D who were at risk of hypoglycaemia were randomized to double‐blind treatment with degludec or insulin glargine 100 units/mL (glargine U100) ± oral antidiabetic drugs. After 32 weeks, patients crossed over to the other treatment. Primary endpoint was number of overall severe (positively adjudicated) or glucose‐confirmed (plasma glucose <56 mg/dL; 3.1 mmol/L) symptomatic hypoglycaemia events during the two 16‐week maintenance periods.ResultsFor individuals ≤65 (n = 450) and >65 (n = 270) years, baseline median (range) duration of diabetes was 12 (1–40) vs 15 (1–54) years, mean HbA1c was 7.7% vs 7.4% and mean estimated glomerular filtration rate was 87.0 vs 63.7 mL/min/1.73 m2, respectively. No significant differences in HbA1c reduction were seen in individuals ≤65 or >65 years. During both maintenance periods, treatment with degludec lowered rates of hypoglycaemia (overall/nocturnal symptomatic) vs those with glargine U100 in individuals ≤65 (31% vs 43%) and >65 (30% vs 41%) years. With degludec and glargine U100, respectively, six vs nine severe hypoglycaemic events occurred in individuals ≤65 years and four vs eight events occurred in those >65 years. Adverse event rates were 3.2 and 3.3 events/patient‐year for individuals ≤65 years and were 3.5 and 4.1 events/patient‐year for individuals >65 years with degludec and glargine U100, respectively.ConclusionTreatment with degludec was safe and effective, with a frequency of hypoglycaemia lower than that with glargine U100 in both younger and older individuals (>65 years) with T2D.

Cardiovascular safety and lower severe hypoglycaemia of insulin degludec versus insulin glargine U100 in patients with type 2 diabetes aged 65 years or older: Results from DEVOTE (DEVOTE 7).

AimsThe aim of this study was to describe the risks of cardiovascular (CV) events and severe hypoglycaemia with insulin degludec (degludec) vs insulin glargine 100 units/mL (glargine U100) in patients with type 2 diabetes (T2D) aged 65 years or older.Materials and methodsA total of 7637 patients in the DEVOTE trial, a treat‐to‐target, randomized, double‐blind trial evaluating the CV safety of degludec vs glargine U100, were divided into three age groups (50‐64 years, n = 3682; 65‐74 years, n = 3136; ≥75 years, n = 819). Outcomes by overall age group and randomized treatment differences were analysed for major adverse cardiovascular events (MACE), all‐cause mortality, severe hypoglycaemia and serious adverse events (SAEs).ResultsPatients with increasing age had higher risks of CV death, all‐cause mortality and SAEs, and there were non‐significant trends towards higher risks of MACE and severe hypoglycaemia. Treatment effects on the risk of MACE, all‐cause mortality, severe hypoglycaemia and SAEs were consistent across age groups, based on the non‐significant interactions between treatment and age with regard to these outcomes.ConclusionsThere were higher risks of CV death, all‐cause mortality and SAEs, and trends towards higher risks of MACE and severe hypoglycaemia with increasing age after adjusting for baseline differences. The effects across age groups of degludec vs glargine U100 on MACE, all‐cause mortality and severe hypoglycaemia were comparable, suggesting that the risk of MACE, as well as all‐cause mortality, is similar and the risk of severe hypoglycaemia is lower with degludec regardless of age. Evidence is conclusive only until 74 years of age.

Short-term cost-utility of degludec versus glargine U100 for patients with type 2 diabetes at high risk of hypoglycaemia and cardiovascular events: A Canadian setting (DEVOTE 9).

AimsTo evaluate the short‐term cost‐effectiveness of insulin degludec (degludec) vs insulin glargine 100 units/mL (glargine U100) from a Canadian public healthcare payer perspective in patients with type 2 diabetes (T2D) who are at high risk of cardiovascular events and hypoglycaemia.Materials and methodsA decision analytic model was developed to estimate costs (2017 Canadian dollars [CAD]) and clinical outcomes (quality‐adjusted life years [QALYs]) with degludec vs glargine U100 over a 2‐year time horizon. The model captured first major adverse cardiovascular event, death, severe hypoglycaemia and insulin dosing. Clinical outcomes were informed by a post hoc subgroup analysis of the DEVOTE trial (NCT01959529), which compared the cardiovascular safety of degludec and glargine U100 in patients with T2D who are at high cardiovascular risk. High hypoglycaemia risk was defined as the top quartile of patients (n = 1887) based on an index of baseline hypoglycaemia risk factors.ResultsIn patients at high hypoglycaemia risk, degludec was associated with mean cost savings (CAD 129 per patient) relative to glargine U100, driven by a lower incidence of non‐fatal myocardial infarction, non‐fatal stroke and severe hypoglycaemia, which offset the slightly higher cost of treatment with degludec. A reduced risk of cardiovascular death and severe hypoglycaemia resulted in improved effectiveness (+0.0132 QALYs) with degludec relative to glargine U100. In sensitivity analyses, changes to the vast majority of model parameters did not materially affect model outcomes.ConclusionOver a 2‐year period, degludec improved clinical outcomes at a lower cost as compared to glargine U100 in patients with T2D at high risk of cardiovascular events and hypoglycaemia.

Efficacy and Safety of Degludec Compared to Glargine 300 Units/mL in Insulin-Experienced Patients With Type 2 Diabetes: Trial Protocol Amendment (NCT03078478).

A head-to-head trial (NCT03078478) between insulin degludec and insulin glargine U300 with the primary objective of comparing the risk of hypoglycemia is being conducted. During trial conduct, safety concerns related to the glycemic data collection system led to a postinitiation protocol amendment, described here. This randomized (1:1), open-label, treat-to-target, multinational trial was initiated in March 2017 with a planned treatment period of 52 weeks (16 weeks titration + 36 weeks maintenance). Overall, ~1600 insulin-experienced patients at risk of developing hypoglycemia based on predefined risk factors were included. The protocol amendment implemented in February 2018 resulted in assuring patient safety and an extension of the total treatment period up to 88 weeks (16 weeks titration + variable maintenance 1 + 36 weeks maintenance 2). The original glycemic data collection system (MyGlucoHealth blood glucose meter + electronic diary) was discontinued because of safety concerns and replaced with an Abbott blood glucose meter and paper diary to collect self-measured blood glucose and hypoglycemic episodes. The primary endpoint of number of severe or blood-glucose confirmed symptomatic hypoglycemic episodes will be evaluated with the same analysis duration and statistical methods as the original protocol. Only relevant changes were implemented to maintain patient safety while permitting evaluation of the scientific objectives of the trial. These observations highlight the importance of safety surveillance during trial conduct despite the use of currently marketed glucose monitoring devices. The prompt protocol amendment and ensuing actions ensured that the scientific integrity of the trial was not compromised.

Lower rates of cardiovascular events and mortality associated with liraglutide use in patients treated with basal insulin: A DEVOTE subanalysis (DEVOTE 10).

AimTo compare the associations between concomitant liraglutide use versus no liraglutide use and the risk of major adverse cardiovascular events (MACE) and all‐cause mortality among patients receiving basal insulin (either insulin degludec [degludec] or insulin glargine 100 units/mL [glargine U100]) in the Trial Comparing Cardiovascular Safety of Insulin Degludec versus Insulin Glargine in Patients with Type 2 Diabetes at High Risk of Cardiovascular Events (DEVOTE).Materials and MethodsPatients with type 2 diabetes and high cardiovascular risk were randomized 1:1 to degludec or glargine U100. Hazard ratios for MACE/mortality were calculated using a Cox regression model adjusted for treatment and time‐varying liraglutide use at any time during the trial, without interaction. Sensitivity analyses were adjusted for baseline covariates including, but not limited to, age, sex, smoking and prior cardiovascular disease.ResultsAt baseline, 436/7637 (5.7%) patients were treated with liraglutide; after baseline, 187/7637 (2.4%) started and 210/7637 (2.7%) stopped liraglutide. Mean liraglutide exposure from randomization was 530.2 days. Liraglutide use versus no liraglutide use was associated with significantly lower hazard rates for MACE [0.62 (0.41; 0.92)95%CI] and all‐cause mortality [0.50 (0.29; 0.88)95%CI]. There was no significant difference in the rate of severe hypoglycaemia with versus without liraglutide use. Multiple sensitivity analyses yielded similar results.ConclusionsUse of liraglutide was associated with significantly lower risk of MACE and death in patients with type 2 diabetes and high cardiovascular risk using basal insulin.

Experience after switching from insulin glargine U100 to glargine U300 in patients with type 1 diabetes mellitus. A study after one year of treatment in real life

IntroductionCurrent treatment of type 1 diabetes mellitus (T1DM) does not always achieve metabolic control because, among other things, the ocurrence of hypoglycemic events associated to insulin use. Material and methodsA descriptive real life study of 247 T1DM patients, 55.5% male, aged 46.53±16.23 years, and with a mean diabetes duration of 21.89±11.99 years, who were switched from basal insulin glargine U100 to glargine U300. The primary endpoints were changes in Hba1c and number of hypoglycemic events, while secondary endpoints included changes in weight and insulin dose after 6 and 12 months. ResultsAfter one year, no changes were seen in HbA1c, but the proportion of patients with HbA1c values <7.5% increased at 6 months (33.5 vs. 40.5%; p<0.05) and remained stable during one year of follow-up. Hypoglycemic events significantly decreased after one year of treatment in patients with previous hypoglycemic events. No changes were seen in body weight.Total insulin dose (U/kg) increased 7.24% at 6 months of treatment and by 8.69% at one year, mainly due to basal insulin. No changes were seen between the doses given at 6 and 12 months. These changes were similar in the different metabolic control groups and in patients with or without hypoglycemia. This increase was not related with prior basal insulin dose, baseline HbA1c level, number of hypoglycemic events or baseline weight. DiscussionGlargine U300 is a good basal insulin alternative to treat T1DM, improving metabolic control in patients with HbA1c levels >7.5 and decreasing hypoglycemic events in patients with history of hypoglycemia without increasing body weight.

Corrections to: Achieving Glycaemic Control withConcentrated Insulin inPatients withType 2 Diabetes.

In several sections of this review article, insulin degludec U100 has been incorrectly referred to as a highly concentrated basal insulin. Although data for both the U100 and U200 formulations of insulin degludec are presented, only insulin degludec U200 and insulin glargine U300 should be referred to as highly concentrated basal insulins.

Developing, Planning and Conducting an Interim Analysis: Lessons From the DEVOTE Cardiovascular Outcomes Trial (Trial Comparing Cardiovascular Safety of Insulin Degludec Versus Insulin Glargine in Patients With Type 2 Diabetes at High Risk of Cardiovascular Events).

In 2013, a randomized, double-blind, active comparator-controlled, event-driven cardiovascular outcomes trial (DEVOTE) was initiated to compare the cardiovascular safety of insulin degludec (degludec) versus insulin glargine 100 units/mL (glargine U100) in patients with type 2 diabetes at high risk of cardiovascular events. The FDA agreed that an interim analysis could form the basis for an early regulatory approval. We report here the operational model developed to support the DEVOTE interim analysis and the results. The interim analysis model was designed to reduce the risk of any confidentiality breaches. The Data Access Management Plan comprehensively described the interim analysis operational processes and procedures to maintain the integrity of the ongoing trial while the interim analysis was conducted, submitted, and acted upon by the FDA, and also until completion of the full trial. Most importantly, those who were unblinded to the interim results were limited to a team of 14 members. A total of 150 first major adverse cardiovascular events were recorded at cut-off for the interim analysis. The estimated hazard ratio was 0.92 (95% CI 0.67, 1.27) and non-inferiority to glargine U100 was confirmed as the upper bound of the confidence interval was below 1.8, as prespecified. Based on these results, the FDA approved the use of degludec and degludec/insulin aspart (IDegAsp) in the United States in 2015 before trial completion. The DEVOTE interim analysis succeeded as a model by which to conduct an interim analysis and submit confidential data for regulatory review and action while continuing the trial to address a primary hypothesis.

Cost of achieving HbA1c and weight loss treatment targets with IDegLira vs insulin glargine U100 plus insulin aspart in the USA.

BackgroundCompared with basal-bolus insulin therapy (insulin glargine U100 plus insulin aspart), IDegLira has been shown to be associated with similar improvements in HbA1c, with superior weight loss and reduced hypoglycemia in patients with type 2 diabetes. The present analysis evaluated the cost per patient with type 2 diabetes achieving HbA1c-focused and composite treatment targets with IDegLira and insulin glargine U100 plus insulin aspart (≤4 times daily).MethodsThe proportions of patients achieving treatment targets were obtained from the treat-to-target, non-inferiority DUAL VII study (NCT02420262). The annual cost per patient achieving target (cost of control) was analyzed from a US healthcare payer perspective. The annual cost of control was assessed for eight prespecified endpoints and four post-hoc endpoints.ResultsThe number needed to treat to bring one patient to targets of HbA1c <7.0% and HbA1c ≤6.5% was similar with IDegLira and insulin glargine U100 plus insulin aspart. However, when weight gain and/or hypoglycemia were included, the number needed to treat was lower with IDegLira. IDegLira and insulin glargine U100 plus insulin aspart had similar costs of control for HbA1c <7.0%. However, cost of control values were substantially lower with IDegLira when the more stringent target of HbA1c ≤6.5% was used, and when patient-centered outcomes of hypoglycemia risk and impact on weight were included.ConclusionIDegLira was shown to be a cost-effective treatment vs insulin glargine U100 plus insulin aspart for patients with type 2 diabetes not achieving glycemic targets on basal insulin in the USA.

Are newer insulin analogues better for people with Type 1 diabetes?

Achieving optimal blood glucose control in Type 1 diabetes is a delicate balance between ensuring tight glycaemic control and achieving this without the expense of hypoglycaemia and weight gain, two major factors impacting quality of life. This is a real challenge for people with Type 1 diabetes and underpins many of the struggles they face in self-managing on a day-to-day basis. The main goals of insulin delivery are to try to simulate the physiology of β-cell insulin secretion as closely as possible and to overcome the challenges of peripheral insulin administration by achieving rapidity of onset with mealtime insulins and stability of the glucose-lowering effects of long-acting insulins. Since the early days of human insulin use, there have been many developments in insulin formulations that aim to achieve these goals as much as possible, thus contributing to better glycaemic control whilst minimizing hypoglycaemia. In the present review we discuss the currently available insulin analogues and the challenges of achieving glucose control using current analogues in those on multiple daily injections, and appraise the evidence base for newer-generation insulin analogues, such as insulin degludec, glargine U300, faster-acting insulin aspart and BioChaperone lispro. We also highlight new insulins in development and unmet needs in people with Type 1 diabetes.

Basal insulin therapy: Unmet medical needs in Asia and the new insulin glargine in diabetes treatment.

Diabetes remains a global epidemic and a tremendous health challenge, especially in the Asian population. Dramatic increases in the prevalence of diabetes across different countries or areas in Asia have been reported in recent epidemiological studies. Although clinical guidelines have strengthened appropriate antihyperglycemic medications and lifestyle modifications for optimal diabetes management, inadequate glycemic control still occurs in many patients with an increased risk of developing microvascular and macrovascular complications. Insulin administration is the main therapy for diabetes in response to the inability to secrete insulin, and is recommended in current guidelines to treat patients with type 2 diabetes after failure of oral antidiabetic drugs. Clinical studies have shown that long‐acting insulin analogs improve basal glycemic control with reduced risk of hypoglycemia. In the present review, we discuss previous challenges with basal insulin therapy in Asia, the pharmacological development of insulin analogs to overcome the unmet medical needs and recent clinical studies of the new ultra‐long‐acting insulin analog, insulin glargine U300. Furthermore, relevant findings of current real‐world evidence are also included for the comparison of the efficacy and safety of different insulin formulations. Based on the accumulating evidence showing a low incidence of hypoglycemia and technical benefits of dose titration, treatment with glargine U300 can be a promising strategy for Asian diabetes patients to achieve glycemic targets with favorable safety.

An observational, multicentre study on different insulin glargine U100 titration algorithms used in patients with type 2 diabetes in daily medical practice in Adriatic countries: The ADRESA study

AimsTo compare the effectiveness of different titration algorithms for insulin glargine U100 used in everyday practice to achieve glycaemic targets in patients with type 2 diabetes mellitus (T2DM). MethodsA total of 526 patients (278 in Slovenia, 248 in Croatia) with T2DM (aged ≥ 18 years) and treated with insulin glargine prior to inclusion were enrolled. Patients self-titrated insulin glargine according to physicians’ guidance. ResultsAmong the 524 patients included in the final analysis, the titration algorithm from the LANMET study was used most commonly (n = 368, 70.5% patients), followed by the Treat-To-Target (TTT) algorithm (n = 117, 22.4%). At the end of the study (6 months), 179 (34.3%) patients reached HbA1c ≤ 7%. There was no significant difference in the proportion of patients who reached their target HbA1c between the different algorithms at 6 months (35.6% using LANMET, 30.7% with TTT, and 32.4% with other algorithms; p = 0.611). HbA1c levels were more significantly reduced in patients using the TTT algorithm compared to LANMET (−2.31%, vs. −1.57%; p < 0.05). The proportion of patients with reported symptomatic hypoglycaemia did not differ significantly between the algorithms. ConclusionsContinuous titration of insulin glargine U100 is a safe and efficient option for T2DM management, regardless of the titration algorithm applied.

Achieving Glycaemic Control with Concentrated Insulin in Patients with Type 2 Diabetes.

The recent introduction of the second-generation long-acting analogue insulins degludec and insulin glargine U300 have increased the choice of basal insulin therapy for patients with type 2 diabetes. The pharmacokinetic and pharmacodynamic properties of these insulins result in a flatter profile that lasts over 24h and provides an increased window of administration of 6h once daily. Large-scale multicentre randomised clinical trial programmes (BEGIN for degludec U100 and U200 and EDITION for glargine U300) evaluating these insulin therapies against glargine U100 have demonstrated that they are either non-inferior or superior for glycaemic efficacy and safety, but less likely to result in severe or nocturnal hypoglycaemia than glargine U100. The disposable pen devices for these insulins have been designed with patient satisfaction and convenience in mind. No concerns have arisen with adverse events with insulin analogues or cardiovascular safety from the ORIGIN and DEVOTE trials. As they demonstrate equivalent glycaemic efficacy to other basal insulins, they should be considered more in selected patient groups including those with recurrent or increased risk of hypoglycaemia, especially severe or nocturnal episodes, in the elderly or those living alone, and in patients with multiple co-morbidities such as cardiovascular or renal disease.

Cardiovascular safety and lower severe hypoglycaemia of insulin degludec versus insulin glargine U100 in patients with type 2 diabetes aged 65 years or older: Results from DEVOTE (DEVOTE 7)

Cardiovascular safety and lower severe hypoglycaemia of insulin degludec versus insulin glargine U100 in patients with type 2 diabetes aged 65 years or older: Results from DEVOTE (DEVOTE 7)

Long-term Cost-effectiveness of Insulin Degludec Versus Insulin Glargine U100 in the UK: Evidence from the Basal-bolus Subgroup of the DEVOTE Trial (DEVOTE 16)

Long-term Cost-effectiveness of Insulin Degludec Versus Insulin Glargine U100 in the UK: Evidence from the Basal-bolus Subgroup of the DEVOTE Trial (DEVOTE 16)