Insulin Analogues Glargine Research Articles

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.

Cost-Effectiveness of Insulin Glargine and Insulin Detemir in the Basal Regimen for Naïve Insulin Patients with Type 2 Diabetes Mellitus (T2DM) in Malaysia.

ObjectiveTo compare the cost-effectiveness of long-acting insulin analogue (LAIA) (insulin Detemir and insulin Glargine) versus NPH insulin in the basal insulin regime for naïve insulin T2DM Malaysian patients.MethodsThe UKPDS-Outcome Model version 2.0 (UKPDS-OM2) was used to evaluate the cost and consequence of diabetes-related complication. The effectiveness of the insulin was derived from the literature review, and the patients’ epidemiology characteristics were retrieved from the Malaysian Diabetes Registry. A discount rate of 3% was applied to both costs and health effects. Another simple mathematical model was used to compare the benefit of reducing the hypoglycemia events between LAIA and NPH insulin. The outputs of the models were combined to obtain the final result. One-way sensitivity analyses were performed to assess the uncertainties.ResultsThe net cost difference (without accounting for hypoglycemia) was RM4868 for insulin Glargine and RM6026 for insulin Detemir. The saving from preventing severe hypoglycemia was RM4377 for insulin Glargine and RM12,753 for insulin Detemir. The total additional QALY gained from insulin Glargine was 0.1317 and from insulin Detemir was 0.8376. The sensitivity analysis shows the discount rate, and drug acquisition cost may affect the incremental cost-effectiveness ratio (ICER) value.ConclusionBoth insulin Detemir and Glargine are cost-effective compared to NPH insulin for T2DM patients, especially when the benefit of reducing the hypoglycemia event rate is taken into account.

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

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

Severe Lipoatrophy in a Patient With Type 2 Diabetes in Response to Human Insulin Analogs Glargine and Degludec: Possible Involvement of CD4 T Cell-Mediated Tissue Remodeling.

Lipoatrophy in response to insulin therapy is a rare condition resulting in a loss of subcutaneous adipose tissue at the site of injection. Since the introduction of humanized insulins, insulin-induced lipoatrophy (IIL) is almost exclusively associated with T1D. IIL was suggested to be an aspect of autoimmunity (1,2), but its underlying pathophysiology is poorly understood. …

Physico-chemical stability of co-formulation of PEGylated human amylin with insulin

Since the discovery of amylin no combined formulation with insulin has been made available. Amylin or its triple proline analog pramlintide are not compatible in solution with insulin. The drug candidate hAmy-PEG5k is a novel monoPEGylated amylin derivative with improved physicochemical properties and retained similar pharmacological activity compared to free amylin and pramlintide. We have investigated the short- and long-term physicochemical compatibility of hAmy-PEG5k co-formulated with slow-acting human insulin analogs glargine or detemir. While human amylin promptly aggregates over a large range of pH, and both free and in the presence of regular, glargine or detemir insulin, the hAmy-PEG5k analog is stable at these conditions as shown by Thioflavin T (ThT) binding assay. When hAmy-PEG5k (100 or 500 µg/mL) was added to the commercial formulations of either insulin glargine or detemir (95 IU/mL), the combinations remained stable after 6 months stored at 4 °C, as probed by ThT, dynamic light scattering (DLS) measurements and high performance liquid chromatography (HPLC) analyses, confirming the absence of amyloid fibers, minor aggregation products or loss of material. These results suggest hAmy-PEG5k and the insulin analogs glargine and detemir are physicochemically compatible and are candidate ready-to-use fixed-dose combinations.

146-OR: Differences in HbA1c-Lowering Effect and Hypoglycemia Risk between Gla-300 and IDeg According to Renal Function in the BRIGHT Trial

BRIGHT demonstrated similar HbA1c reduction and hypoglycemia risk with the second-generation basal insulin analogs insulin glargine 300 U/mL (Gla-300) and insulin degludec 100 U/mL (IDeg) over 24 weeks, and less anytime (24 h) hypoglycemia with Gla-300 during the first 12 weeks, in T2DM. This analysis examined HbA1c change and confirmed (≤70 mg/dL and &amp;lt;54 mg/dL) hypoglycemia by baseline characteristics. BRIGHT was a multicenter, open-label, randomized, active-controlled, parallel-group trial in T2DM. Participants receiving multiple oral agents ± GLP-1 RAs were randomized to Gla-300 (N=466) or IDeg (N=463), titrated to a fasting SMPG of 80-100 mg/dL. Efficacy and safety with Gla-300 vs. IDeg were unaffected by age (≥65 years), gender, BMI category (&amp;lt;30/30-35/≥35 kg/m2) or diabetes duration (≥10 years). However, significant heterogeneity of treatment effect across subgroups (p=0.015) suggested greater HbA1c reduction with Gla-300 than IDeg with impaired renal function (eGFR &amp;lt;60 mL/min/1.73 m2) (Table), with no difference in hypoglycemia incidence or rates. Further analyses revealed lower confirmed (≤70 mg/dL) hypoglycemia rates with Gla-300 vs. IDeg in those with normal renal function, with comparable HbA1c reduction (Table). In conclusion, Gla-300 appears to confer advantages vs. IDeg in those with impaired renal function, warranting further investigation. Disclosure M. Haluzik: Advisory Panel; Self; AstraZeneca, Medtronic, Merck &amp; Co., Inc., Novo Nordisk A/S, Sanofi. Consultant; Self; Johnson &amp; Johnson, Lilly Diabetes. Speaker's Bureau; Self; Novartis AG. A. Philis-Tsimikas: Advisory Panel; Self; AstraZeneca, Lilly Diabetes, Novo Nordisk A/S, Sanofi. Employee; Spouse/Partner; Ionis Pharmaceuticals, Inc. Research Support; Self; Dexcom, Inc., Glooko, Inc., National Institute of Diabetes and Digestive and Kidney Diseases. Stock/Shareholder; Spouse/Partner; Ionis Pharmaceuticals, Inc., Novo Nordisk Inc. Z. Bosnyak: Employee; Self; Sanofi. Stock/Shareholder; Self; Sanofi. D. Müller-Wieland: Advisory Panel; Self; Amgen Inc., AstraZeneca, Bayer AG, Boehringer Ingelheim Pharmaceuticals, Inc., Merck Sharp &amp; Dohme Corp., Novo Nordisk Inc., Sanofi-Aventis Deutschland GmbH. Speaker's Bureau; Self; Amgen Inc., AstraZeneca, Bayer AG, Boehringer Ingelheim Pharmaceuticals, Inc., Merck Sharp &amp; Dohme Corp., Novo Nordisk Inc., Sanofi-Aventis Deutschland GmbH. F. Lauand: Employee; Self; Sanofi. L. Melas-Melt: Consultant; Self; Sanofi. J. Rosenstock: Research Support; Self; AstraZeneca, Bristol-Myers Squibb Company, Genentech, Inc., GlaxoSmithKline plc., Lexicon Pharmaceuticals, Inc., Melior Pharmaceuticals, Inc., Bukwang Pharm. Co., Ltd., Merck &amp; Co., Inc., Oramed Pharmaceuticals, PegBio Co., Ltd., Pfizer Inc. Other Relationship; Self; Boehringer Ingelheim International GmbH, Eli Lilly and Company, Intarcia Therapeutics, Inc., Janssen Pharmaceuticals, Inc., Novo Nordisk Inc., Sanofi. G.B. Bolli: Advisory Panel; Self; Sanofi. Research Support; Self; A. Menarini Diagnostics, Medtronic. Funding Sanofi (NCT02738151)

1098-P: Treatment Satisfaction with Gla-300, IDeg-100, and Gla-100 in Insulin-Naïve T2DM: The BRIGHT and EDITION 3 Trials

Long-acting insulin analogs have the potential to optimize glycemic control in type 2 diabetes, but the patients’ perspective is key for acceptance and treatment adherence. BRIGHT investigated safety and efficacy of initiating the second-generation basal insulin analogs insulin glargine 300 U/mL (Gla-300) vs. insulin degludec 100 U/mL (IDeg-100) in insulin-naïve people with T2DM. We report data on patient satisfaction from the BRIGHT trial and the EDITION 3 trial (Gla-300 vs. insulin glargine 100 U/mL [Gla-100]). BRIGHT and EDITION 3 were both multicenter, open-label, randomized, parallel-group trials with primary endpoint at 6 months. Randomized participants titrated to a fasting SMPG of 80-100 mg/dL (once-daily evening dosing). The Diabetes Treatment Satisfaction Questionnaire (DTSQ) was completed at baseline and 6 months. Overall, initiating basal insulin analogs was associated with improved treatment satisfaction (Table). There was a numerically greater decrease in perceived hyperglycemia frequency for Gla-300 and IDeg-100 vs. Gla-100 and only a very small increase in the perceived hypoglycemia frequency for all insulins. Similar treatment satisfaction improvement for all insulins was observed. In randomized controlled trials, initiating basal insulin analogs is associated with improved treatment satisfaction, with little increase in perceived hypoglycemia frequency. Disclosure L. Berard: Advisory Panel; Self; Eli Lilly and Company. Consultant; Self; Abbott, Ascensia Diabetes Care, AstraZeneca, Bayer AG, Becton, Dickinson and Company, Janssen Pharmaceuticals, Inc., LifeScan Canada, Mylan, Novo Nordisk Inc., Sanofi. Research Support; Self; Montmed Inc. Speaker's Bureau; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Merck &amp; Co., Inc. F.J. Snoek: Advisory Panel; Self; AstraZeneca, Lilly Diabetes, Novo Nordisk A/S, Roche Diabetes Care. Research Support; Self; Sanofi. Speaker's Bureau; Self; Lilly Diabetes. S.B. Harris: Advisory Panel; Self; AstraZeneca, Janssen Pharmaceuticals, Inc., Lilly/Boehringer Ingelheim, Merck &amp; Co., Inc., Novo Nordisk A/S, Sanofi. Consultant; Self; AstraZeneca, Janssen Pharmaceuticals, Inc., Lilly/Boehringer Ingelheim, Merck &amp; Co., Inc., Novo Nordisk Inc., Sanofi. Research Support; Self; Abbott, AstraZeneca, Janssen Pharmaceuticals, Inc., Merck &amp; Co., Inc., Novo Nordisk A/S, Sanofi. Other Relationship; Self; Canadian Diabetes Association, Canadian Institutes of Health Research, The Lawson Foundation. J. Westerbacka: Employee; Self; Sanofi. Stock/Shareholder; Self; Sanofi. Z. Bosnyak: Employee; Self; Sanofi. Stock/Shareholder; Self; Sanofi. L. Melas-Melt: Consultant; Self; Sanofi. K. Khunti: Advisory Panel; Self; Amgen Inc., AstraZeneca, Eli Lilly and Company, Merck Sharp &amp; Dohme Corp., Novo Nordisk A/S, Sanofi. Consultant; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Janssen Pharmaceuticals, Inc., Merck Sharp &amp; Dohme Corp., Novartis AG, Novo Nordisk A/S, Pfizer Inc., Sanofi-Aventis, Servier, Takeda Pharmaceutical Company Limited. Research Support; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Merck Sharp &amp; Dohme Corp., Novartis AG, Novo Nordisk A/S, Pfizer Inc., Sanofi-Aventis. Speaker's Bureau; Self; AstraZeneca, Berlin-Chemie AG, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Janssen Pharmaceuticals, Inc., Menarini Group, Merck Sharp &amp; Dohme Corp., Novartis AG, Novo Nordisk A/S, Roche Pharma, Sanofi, Servier, Takeda Pharmaceutical Company Limited. Funding Sanofi (NCT02738151)

Differentiating Basal Insulin Preparations: Understanding How They Work Explains Why They Are Different.

Since the introduction of insulin as a life-saving agent for patients with type 1 diabetes, insulin preparations have evolved to approximate physiologic insulin delivery profiles to meet prandial and basal insulin needs. While prandial insulins are designed to have quick time–action profiles that minimize postprandial glucose excursions, basal insulins are designed to have a protracted time–action profile to facilitate basal glucose control over 24 h. Given that all insulins have the same mechanism of action at the target tissue level, the differences in time–action profiles are achieved through different mechanisms of protraction, resulting in different behaviors in the subcutaneous space and different rates of absorption into the circulation. Herein, we evaluate the differences in basal insulin preparations based on their differential mechanisms of protraction, and the resulting clinical action profiles. Multiple randomized control trials and real-world evidence studies have demonstrated that the newer second-generation basal insulin analogs, insulin glargine 300 units/mL and insulin degludec 100 or 200 units/mL, provide stable glycemic control with once-daily dosing and are associated with a reduced risk of hypoglycemia compared with previous-generation basal insulin analogs insulin glargine 100 units/mL and insulin detemir. These advantages can lead to decreased healthcare resource utilization and cost. With this collective knowledge, healthcare providers and payers can make educated and well-informed decisions when determining which treatment regimen best meets the needs of each individual patient.Funding: Sanofi US, Inc.

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.

Comparison of the efficacy and safety of once-daily insulin degludec/insulin aspart (IDegAsp) and long-acting second-generation basal insulin (insulin degludec and insulin glargine 300 units/mL) in insulin-naïve Japanese adults with type 2 diabetes: a pilot, randomized, controlled study.

To examine the efficacy and safety of once-daily insulin degludec/insulin aspart (IDegAsp) or once-daily second-generation basal insulin analogs (insulin degludec and insulin glargine 300 units/mL) in insulin-naïve Japanese adults with type 2 diabetes in routine clinical practice. A 12-week multicenter, open-label, randomized, pilot study was performed in 52 subjects with type 2 diabetes treated with oral antidiabetic drugs (OADs). Subjects were randomized to once-daily IDegAsp (n = 26) or basal insulin (n = 26). The primary endpoint was percent change in HbA1c from baseline to week 12. Furthermore, it was analyzed post hoc in subgroups stratified by baseline HbA1c. During a follow-up period, percent change in HbA1c was not significantly different between the two groups (p = 0.161). Daily insulin doses and frequency of overall hypoglycemia were also similar in the two groups. In post hoc analyses, once-daily basal insulin was more effective than IDegAsp in subjects with HbA1c more than or equal to 8.5% (p < 0.05); however, in subjects with HbA1c less than 8.5%, once-daily IDegAsp showed a significant improvement in percent change in HbA1c at week 12, compared with basal insulin (p < 0.01). Although there was no apparent difference in the HbA1c-lowering effects between two groups, when compared in subjects with HbA1c less than 8.5%, once-daily IDegAsp showed a significant effect in comparison with once-daily basal insulin. These findings suggest that the baseline HbA1c level might provide the important information for choosing IDegAsp or basal insulin in patients insufficiently controlled with OADs. This trial was registered with UMIN (no. UMIN000035431).

PDB11 - CHART REVIEW ANALYSIS OF INSULIN GLARGINE 300 AND INSULIN GLARGINE 100 USE IN FRANCE, SPAIN, AND GERMANY

In randomized controlled trials (RCTs) and real-world (RW) studies, adult patients (pts) with type 2 diabetes (T2D) treated with basal insulin (BI) analogues insulin glargine 300 U/ml (Gla-300) or insulin glargine 100 U/ml (Gla-100) had similar reductions in HbA1c and Gla-300 was associated with lower incidence of hypoglycaemia compared with Gla-100. This study evaluated clinical outcomes in pts with T2D who switched from any BI to Gla-300 or Gla-100 in France, Spain, and Germany. Interim data were obtained from medical records for 494 pts who switched to either Gla-300 (N=292) or Gla-100 (N=202). Differences in baseline (BL) characteristics and clinical outcomes between groups were evaluated, and physician reasons for selecting Gla-300 or Gla-100 were assessed. Patient demographics and comorbidities were generally similar between Gla-300 and Gla-100 groups: % female (39.4 vs 47.0%, respectively), mean BL HbA1c (8.4 vs 8.4%), Charlson Comorbidity Index score (0.78 vs 0.88). In the Gla-300 group, diabetic nephropathy (7.2 vs 2.5%; P=0.021), prior stroke/TIA (7.2 vs 2.5%; P=0.021), and BMI (mean 29.2 vs 28.4 kg/m2; P=0.024) was higher, and more pts reported any hypoglycaemic events prior to switch (37.0 vs 24.3%; P=0.012). At 6 months’ follow-up, reductions from BL in HbA1c (-1.07 vs -1.16%) and weight (-2.29 vs -2.09 kg) were similar. The unadjusted mean reduction in hypoglycaemic events/patient over 6 months was greater for Gla-300 (-1.29 vs -0.62; P=0.025). There were no meaningful differences in insulin dose change during the reported titration period (5.53 vs 6.00 U). This comparative EU study showed that at 6 months, changes in glycaemic control and weight from BL were similar; however, unadjusted reductions in hypoglycaemic events were greater for pts switching to Gla-300 than to Gla-100, as previously reported in RCTs and RW studies. Here, there was no difference in dose change 6 months after switching.

A practical guide to the interpretation of PK/PD profiles of longer-acting analogue insulins. Part two: Insulin degludec vs. insulin glargine U300

Glucose clamp studies form an integral part of the early development of insulin therapies. Data generated in these studies are used to establish pharmacokinetic (PK) and pharmacodynamic (PD) profiles of the agents, but methodological differences confound comparison of results from different glucose clamp studies. The first part of this series on glucose clamp studies discussed practical tips for the interpretation of glucose clamp studies. The second part of the series compares the PK/PD profiles of longer-acting basal analogue insulins, insulin degludec (IDeg) and insulin glargine U300 (Gla-300). The patient populations for glucose clamp studies with these analogue insulins differ, and therefore direct comparison of the data is not always possible. The maximum duration of action of IDeg is reported as 42 h and that of Gla-300 as 36 h, translating to 24 h coverage. The plasma insulin concentration of IDeg is 56 times that of Gla-300. Results from phase III clinical trials for these analogue insulins confirm the predictability and low within-subject variability observed in glucose clamp studies. Insight into the PK/PD profiles of longer-acting basal analogue insulins allows the treating physician to utilise these characteristics to optimise the treatment of their patients with diabetes.

Long-term exposure to insulin and volumetric mammographic density: observational and genetic associations in the Karma study

BackgroundLong-term insulin exposure has been implicated in breast cancer etiology, but epidemiological evidence remains inconclusive. The aims of this study were to investigate the association of insulin therapy with mammographic density (MD) as an intermediate phenotype for breast cancer and to assess associations with long-term elevated circulating insulin levels using a genetic score comprising 18 insulin-associated variants.MethodsWe used data from the KARolinska MAmmography (Karma) project, a Swedish mammography screening cohort. Insulin-treated patients with type 1 (T1D, n = 122) and type 2 (T2D, n = 237) diabetes were identified through linkage with the Prescribed Drug Register and age-matched to 1771 women without diabetes. We assessed associations with treatment duration and insulin glargine use, and we further examined MD differences using non-insulin-treated T2D patients as an active comparator. MD was measured using a fully automated volumetric method, and analyses were adjusted for multiple potential confounders. Associations with the insulin genetic score were assessed in 9437 study participants without diabetes.ResultsCompared with age-matched women without diabetes, insulin-treated T1D patients had greater percent dense (8.7% vs. 11.4%) and absolute dense volumes (59.7 vs. 64.7 cm3), and a smaller absolute nondense volume (615 vs. 491 cm3). Similar associations were observed for insulin-treated T2D, and estimates were not materially different in analyses comparing insulin-treated T2D patients with T2D patients receiving noninsulin glucose-lowering medication. In both T1D and T2D, the magnitude of the association with the absolute dense volume was highest for long-term insulin therapy (≥ 5 years) and the long-acting insulin analog glargine. No consistent evidence of differential associations by insulin treatment duration or type was found for percent dense and absolute nondense volumes. Genetically predicted insulin levels were positively associated with percent dense and absolute dense volumes, but not with the absolute nondense volume (percentage difference [95% CI] per 1-SD increase in insulin genetic score = 0.8 [0.0; 1.6], 0.9 [0.1; 1.8], and 0.1 [− 0.8; 0.9], respectively).ConclusionsThe consistency in direction of association for insulin treatment and the insulin genetic score with the absolute dense volume suggest a causal influence of long-term increased insulin exposure on mammographic dense breast tissue.

Long-Acting Insulin Analogues and Risk of Breast Cancer—Meta-analysis

Observational studies on the association between prescription of long acting insulin analogues (glargine and detemir) and the risk of breast cancer (BC) report conflicting results. We performed a meta-analysis of prospective studies on the risk of breast cancer among diabetic patients exposed to long acting insulin analogues following PRISMA guidelines. Summary relative risks (SRR) were computed using a random-effect model. Thirteen studies were identified which reported data on insulin glargine which included 438,214 subjects and 4,041 BC cases over a median follow-up of 2.8 years. In 11 studies, including 94.8 % of BC, the comparator groups included diabetic patients treated with non-glargine insulin. The SRR was 1.11 (95% CI: 0.98, 1.24), with little heterogeneity (I2=27%). Among prevalent users of insulin, based on 7 studies, the SRR of BC (1,425 cases) associated with prescription of glargine was 1.(95% CI: 0.90, 1.23), with moderate heterogeneity among studies (I2=40%). One influential study (Wu et al. 2017) accounted for most of the heterogeneity. When it was removed from the meta-analysis, the I2 dropped to 0% with a SRR of 0.99 (95% CI: 0.88, 1.12). Among new users of insulin, based on 10 studies, the SRR of BC (3,847 cases) associated with prescription of glargine was 1.12 (95% CI: 0.96, 1.29), with moderate heterogeneity among studies (I2=41%). One influential study (Ruiter et al. 2012) accounted for most of the heterogeneity. When it was removed from the meta-analysis, the I2 dropped to 0% with a SRR of 1.07 (95% CI: 0.96, 1.21). Only three studies reported on detemir, with a SRR for BC (1,947 cases) of 1.09 (95% CI: 0.77, 1.57). There seems to be consistent evidence showing no association between the prescription of long acting insulins and risk of BC. However, most of these studies had a short duration of follow-up. In addition, only three studies were identified reporting the risk of BC associated with use of detemir. Disclosure M. Bota: None. P. Autier: Other Relationship; Self; Sanofi. P. Boyle: Other Relationship; Self; Sanofi.

Development of a New HPLC Method for the Determination of Lispro and Glargine Insulin Analogues in Pharmaceutical Preparations

Development of a New HPLC Method for the Determination of Lispro and Glargine Insulin Analogues in Pharmaceutical Preparations

Quality of Life of Patients with Type 1 Diabetes Mellitus Using Insulin Analog Glargine Compared with NPH Insulin: A Systematic Review and Policy Implications.

IntroductionInsulin analog glargine (GLA) has been available as one of the therapeutic options for patients with type 1 diabetes mellitus to enhance glycemic control. Studies have shown that a decrease in the frequency of hypoglycemic episodes improves the quality of life (QoL) of diabetic patients. However, there are appreciable acquisition cost differences between different insulins. Consequently, there is a need to assess their impact on QoL to provide future guidance to health authorities.MethodA systematic review of multiple databases including Medline, LILACS, Cochrane, and EMBASE databases with several combinations of agreed terms involving randomized controlled trials and cohorts, as well as manual searches and gray literature, was undertaken. The primary outcome measure was a change in QoL. The quality of the studies and the risk of bias was also assessed.ResultsEight studies were eventually included in the systematic review out of 634 publications. Eight different QoL instruments were used (two generic, two mixed, and four specific), in which the Diabetes Treatment Satisfaction Questionnaire (DTSQ) was the most used. The systematic review did not consistently show any significant difference overall in QoL scores, whether as part of subsets or combined into a single score, with the use of GLA versus neutral protamine Hagedorn (NPH) insulin. Only in patient satisfaction measured by DTSQ was a better result consistently seen with GLA versus NPH insulin, but not using the Well-being Inquiry for Diabetics (WED) scale. However, none of the cohort studies scored a maximum on the Newcastle–Ottawa scale for quality, and they generally were of moderate quality with bias in the studies.ConclusionThere was no consistent difference in QoL or patient-reported outcomes when the findings from the eight studies were collated. In view of this, we believe the current price differential between GLA and NPH insulin in Brazil cannot be justified by these findings.Electronic supplementary materialThe online version of this article (10.1007/s40271-017-0291-3) contains supplementary material, which is available to authorized users.

PP142 Is Insulin Therapy Important For The Quality Of Life Of Diabetics?

Introduction:Quality of life (QoL) is an important health measure and is widely used to assess the difference between treatments for Type 1 Diabetes Mellitus (T1DM) since the desirable glycemic control and the minimization of episodes of hypoglycemia are fundamental aspects for a better QoL. This study aims to identify the factors associated with QoL in patients with T1DM.Methods:A cross-sectional study (approved by ethics committee) was carried out in the state of Minas Gerais with 401 T1DM patients who used insulin glargine (GLA) selected in March 2017, and 179 patients who used insulin-neutral protamine (NPH) selected between January and February 2014, and both groups were treated by Brazilian National Health System (SUS). A questionnaire with three blocks was used: A) sociodemographic data; B) clinical data and access to the service; and C) QoL by Euroqol (EQ-5D-3L). We used multiple linear regression model by the forward stepwise method to access the correlation between the utilities of the EQ-5D-3L and all the explanatory variables (blocks A and B). We adopted the significance level and confidence interval of 95 percent (95% CI).Results:Of the 580 patients evaluated, 54 percent were women, 47 percent were in the age group between 18–40 years, 53 percent reported to be non-black. The EQ-5D-3L analysis showed patients treated with insulin analogue GLA had an average utility of 0.849 and those treated with NPH insulin 0.722 (p &lt; 0.000). Individuals young, very good/good health self-perception, having not been bedridden in the last 15 days, zero to three medical appointments in the last year, no hospitalization in the last year, regular physical activity in the last 15 days to practice physical exercise, having between zero and three comorbidities and no severe hypoglycemia in the last 30 days were explained 41.3 percent of QoL. The type of insulin therapy, GLA or NPH, did not enter into the final multiple regression model.Conclusions:The findings of this study pointed to a lack of correlation between insulin therapy and QoL of patients with T1DM. Sociodemographic and clinical factors were more important to explain the QoL of diabetics. In addition, the evidence pointed to the importance of episodes of hypoglycemia for Qol. Of the 191 episodes of hypoglycemia (non-severe and severe) reported, 66 percent were from patients treated with GLA.

Second-Generation Insulin Analogues - a Review of Recent Real-World Data and Forthcoming Head-to-Head Comparisons.

Insulin analogues play a key role in the effective management of type 2 diabetes. However, there are several behavioural barriers to appropriate early initiation of insulin therapy, despite compelling evidence supporting the benefits of this strategy in those patients for whom oral anti-diabetes agents provide insufficient control. The development of second-generation insulin analogues (insulin glargine 300 U/mL and insulin degludec) has provided physicians with agents that can provide comparable glycaemic control to first-generation insulin, but with a reduced risk of hypoglycaemia and modes of action suited to once-daily regimens. These characteristics may help overcome patient and physician concerns about early insulin use in disease management. To date, there have been no head-to-head comparisons of second-generation insulins: here we consider recent real-world evidence and the forthcoming direct comparison in the BRIGHT randomised controlled study, as presented at the recent 11th International Conference on Advanced Technologies & Treatments for Diabetes (ATTD) 2018.

Insulin analogues glargine 300 U/mL and 100 U/mL: The same active principle for two different drugs

Insulin analogues glargine 300 U/mL and 100 U/mL: The same active principle for two different drugs