Glargine U100 Research Articles

606-P: Higher Derived Time-in-Range with IDegLira vs. Insulin Glargine U100 in Patients with T2D

Aims: To compare derived time in range (dTIR) with insulin degludec/liraglutide (IDegLira) and insulin glargine 100 units/mL (IGlar U100) in patients with type 2 diabetes (T2D). Methods: Data from DUAL V, a trial of patients with T2D uncontrolled on IGlar U100 randomized to switch to IDegLira or up-titration of IGlar U100 (+metformin; n=557), and DUAL VIII, a durability trial of insulin-naive patients with T2D randomized to either IDegLira or IGlar U100 (+ oral antidiabetic drugs; n=1012), were evaluated post hoc. Self-monitored blood glucose profiles (weeks 0, 12, and 26 [DUAL V] or weeks 0, 26, and 104 [DUAL VIII]) were used to derive the proportion of available readings within (dTIR: 70-180 mg/dL [3.9-10 mmol/L]), below (dTBR: 180 mg/dL [>10 mmol/L]) target range. Results: Estimated treatment differences (IDegLira− IGlar U100) for change from baseline to end of treatment (EOT) in dTIR were significantly greater with IDegLira vs. IGlar U100 (Figure). The proportion of patients achieving ≥70% dTIR at EOT with IDegLira and IGlar U100, respectively, was 62% and 60% in DUAL V, and 50% and 26% in DUAL VIII; the proportion achieving a ≥5% increase in dTIR from baseline to EOT was 63% in both groups in DUAL V, and 44% and 25%, respectively, in DUAL VIII. Conclusion: IDegLira was associated with significantly greater dTIR vs. IGlar U100 in insulin-experienced and insulin-naive patients with T2D. Disclosure A. Philis-tsimikas: Advisory Panel; Self; Bayer Inc., Lilly Diabetes, Medtronic, Novo Nordisk, Consultant; Self; Sanofi-Aventis, Employee; Spouse/Partner; Ionis, Other Relationship; Self; Merck & Co., Inc., Research Support; Self; Dexcom, Inc., Lilly Diabetes, Medtronic, Novo Nordisk, Sanofi-Aventis. V. R. Aroda: Consultant; Self; Applied Therapeutics, Duke, Novo Nordisk, Pfizer Inc., Sanofi, Employee; Spouse/Partner; Janssen , Merck , Research Support; Self; Applied Therapeutics, Eli Lilly and Company, Fractyl , Medpace, Medpace, Novo Nordisk, Premier , Sanofi, Stock/Shareholder; Spouse/Partner; Janssen, Merck. C. De block: Advisory Panel; Self; A. Menarini Diagnostics, Abbott Diagnostics, AstraZeneca, Boehringer Ingelheim , Eli Lilly and Company, MSD, Novartis AG, Novo Nordisk, Roche Diagnostics, Sanofi, Research Support; Self; AstraZeneca, Novo Nordisk, Speaker9s Bureau; Self; A. Menarini Diagnostics, Abbott Diagnostics, Boehringer Ingelheim , Eli Lilly and Company, Novo Nordisk, Sanofi. L. K. Billings: Advisory Panel; Self; Bayer Inc., Lilly Diabetes, Novo Nordisk, Sanofi. E. Hachmann-nielsen: Employee; Self; Novo Nordisk A/S. A. Liebl: Advisory Panel; Self; AstraZeneca, Becton, Dickinson and Company, Boehringer Ingelheim International GmbH, Eli Lilly and Company, MSD, Novo Nordisk, Roche, Speaker9s Bureau; Self; AstraZeneca, Bayer, Becton, Dickinson and Company, Boehringer Ingelheim International GmbH, Bristol Myers Squibb , Dexcom, Inc., Eli Lilly and Company, Medtronic, MSD, Novo Nordisk, OmniaMed, Roche, Sanofi. R. Sivarathinasami: Employee; Self; Novo Nordisk Service Centre India Private Ltd. J. M. D9cruz: Employee; Self; NovoNordisk GBS. I. Lingvay: Advisory Panel; Self; Bayer Healthcare Pharmaceuticals Inc., Lilly Diabetes, Consultant; Self; TARGET PharmaSolutions, Other Relationship; Self; Boehringer Ingelheim Pharmaceuticals, Inc., Merck Sharp & Dohme Corp., Novo Nordisk, Pfizer Inc., Zealand Pharma A/S, Research Support; Self; Mylan N. V., Sanofi. Funding Novo Nordisk A/S

731-P: CGM-Based Measurements for Once-Weekly Insulin Icodec vs. Once-Daily Insulin Glargine U100 in Insulin-Treated Patients with T2D: A Post-hoc Analysis

Insulin icodec* (icodec) is a once-weekly basal insulin in clinical development. In a phase 2 treat-to-target trial (NCT03922750) in patients with T2D switching from daily insulin (N=154), icodec with an initial 100% loading dose (LD; doubling the first dose) showed greater time in range (TIR, 70-180 mg/dL) vs. insulin glargine U100 (IGlar U100) at weeks 15 and 16 (primary endpoint), as measured by double-blinded Dexcom G6® CGM. This post hoc analysis compared TIR, time above range (TAR, >180 mg/dL) and below range (TBR, 70% TIR and Disclosure H. S. Bajaj: Other Relationship; Self; Eli Lilly and Company, Novo Nordisk, Research Support; Self; Amgen Inc., AstraZeneca, Boehringer Ingelheim International GmbH, Gilead Sciences, Inc., Kowa Pharmaceuticals America, Inc., Merck & Co., Inc., Sanofi, Tricida, Inc. R. Beck bang: Employee; Self; Novo Nordisk A/S. A. Gowda: Employee; Self; Novo Nordisk A/S, Stock/Shareholder; Self; Novo Nordisk A/S. M. M. Koefoed: Employee; Self; Novo Nordisk. P. A. Senior: Other Relationship; Self; Novo Nordisk, Vertex Pharmaceuticals Incorporated, Research Support; Self; Novo Nordisk. R. M. Bergenstal: Advisory Panel; Self; Abbott Diabetes, Eli Lilly and Company, Novo Nordisk, Onduo LLC., Roche , Sanofi, United Healthcare , Consultant; Self; Abbott Diabetes, Ascensia , Dexcom, Inc., Eli Lilly and Company, Hygieia, Johnson & Johnson, Medtronic, Novo Nordisk, Onduo LLC., Roche, Sanofi, United Healthcare, Other Relationship; Self; HealthPartners Institute, Research Support; Self; Abbott Diabetes, Dexcom, Inc., Eli Lilly and Company, Helmsley Charitable Trust, Hygieia, Johnson & Johnson, Medtronic, NIDDK, Novo Nordisk, Onduo LLC., Roche, Sanofi, United Healthcare.

Real-World Use of Insulin Glargine U100 and U300 in Insulin-Naïve Patients with Type 2 Diabetes Mellitus: DosInGlar Study.

IntroductionIn the EDITION clinical trial programme, patients with type 2 diabetes mellitus (T2DM) receiving insulin glargine (IGlar) U300 required 10–15% more insulin than those receiving IGlar U100. This study sought to determine whether this difference was apparent in real-world practice.MethodsIn this observational, retrospective cohort study, electronic medical records in the Big-Pac® database (Real Life Data) relating to adult insulin-naïve patients with T2DM who initiated IGlar U100 or U300 treatment in Spain in 2016–2017 and remained on treatment for 18 months were selected. IGlar U100- and U300-treated patients were matched 1:1 (propensity score matching). The primary analysis compared changes from baseline in mean daily IGlar dose (U and U/kg) at 6 (± 2), 12 (± 2) and 18 (± 2) months between cohorts (paired t tests). Changes in glycated haemoglobin (HbA1c) and weight were analysed descriptively.ResultsThe IGlar U100 and U300 cohorts included 556 matched pairs (46.9% female) with the following mean (standard deviation) values at baseline, respectively: age 63.6 (12.8) versus 63.7 (11.9) years; years since diagnosis 9.5 (1.4) versus 9.5 (1.3); HbA1c 8.8 (1.3) versus 8.7 (1.5) %; weight 84.6 (16.9) versus 84.7 (17.1) kg. Mean IGlar dose at baseline was 0.19 U/kg/day (both cohorts). Patients receiving IGlar U300 showed a greater increase from baseline in IGlar dose at 6, 12 and 18 months [mean dose (U/kg/day) 5.1%, 10.3% and 12.8% greater, respectively, in IGlar U300-treated patients]. Mean HbA1c was 8.1% in both cohorts at 18 months. Mean (SD) weight at 18 months with IGlar U100 and IGlar300 was 86.8 (17.0) kg and 85.0 (17.1) kg, respectively.ConclusionIn real-world practice, insulin dose was significantly higher in IGlar U300-treated than U100-treated patients at 6, 12 and 18 months, with similar reductions in HbA1c. At equal IGlar price/unit in Spain, the increased dose requirements of IGlar U300 would result in higher costs.Supplementary InformationThe online version contains supplementary material available at 10.1007/s12325-021-01773-z.

Clinical research of insulin glargine U300 basal-bolus therapy and insulin degludec/aspart co-formulation in type 2 diabetes mellitus: A real world experience.

Insulin degludec/aspart (IDegAsp) and insulin glargine U300 (IGlarU300) have recently emerged as popular new-generation insulin analogues. The aim of this real-life study was to investigate the patient profiles in which IGlarU300 and IDegAsp were preferred and the insulin combinations after which each of them were mostly used and also to analyse the effect of these two insulin analogues on blood glucose regulation and hypoglycaemia. The retrospective study included 174 patients that were switched from basal insulin, basal-bolus insulin, or premixed insulin to IGlarU300 or IDegAsp due to uncontrolled blood glucose levels or history of hypoglycaemia. Hypoglycaemia, body weight, body mass index (BMI), fasting plasma glucose (FPG) and HbA1c levels over 3-month periods were evaluated for each patient. There were 84 and 90 patients in the IGlarU300 and IDegAsp groups, respectively. Body weight was similar in both groups. Baseline FPG and HbA1c levels in the IGlarU300 and IDegAsp groups were 9.0%, 175.5mg/dL and 9.4%, 193.5mg/dL, respectively. A significant decrease was found in FPG and HbA1c levels in both groups (138.5, 7.8 vs 141.5, 8.2; P<.001 for all). Moreover, a significant weight gain was observed in both groups (P<.05 for both). The prevalence of hypoglycaemia in both groups decreased significantly and consistently between months 1 and 9 (P<.001). At month 12, although this decrease continued in the IGlarU300 group (P=.013), no significant decrease was observed in the IDegAsp group (P=.057). Both twice-daily IDegAsp±bolus insulin and IGlarU300 basal bolus insulin therapies are effective and safe treatment modalities.

Clinical Characteristics of Withdrawal of Basal Insulin Therapy Among Japanese Patients with Type 2 Diabetes: A Multicenter Retrospective Observational Study.

IntroductionThis study aimed to examine retrospectively the clinical backgrounds of Japanese patients with type 2 diabetes (T2D) who successfully withdrew from insulin use after being started on basal insulin in an outpatient setting.MethodsThe study population comprised 376 insulin-naïve patients who were started on basal insulin (glargine U100, glargine U300, or degludec) for the management of T2D and followed the treatment regimen for at least 6 months in 13 institutions in Japan. The clinical courses of the study participants were compared based on outpatient clinic medical records for the three different types of basal insulin prescribed by categorizing the participants into two groups retrospectively: those who successfully withdrew from insulin therapy and those who did not, during a 6-month observation period. The clinical determinants for insulin withdrawal were assessed using a Cox proportional hazard model.ResultsGlycated hemoglobin was improved in all participants regardless of basal insulin type. Of the 376 study participants, 61 successfully withdrew from basal insulin therapy. After adjustment was made for several confounders, the positive determinant factors for successful withdrawal of insulin were short duration of diabetes and high body mass index at the start of study, and the negative determinant factor was use of insulin secretagogues at the start. The types of basal insulin used by the study participants were not significant determinants of successful insulin withdrawal in this study.ConclusionsUse of basal insulin is a powerful option for the treatment of T2D. In patients with high BMI and/or short duration of diabetes, short-term insulin therapy is a promising strategy for the treatment of T2D before the initiation of insulin secretagogues, since such patients have the potential to successfully withdraw from basal insulin use even in an outpatient setting.

Duration of type 2 diabetes does not appear to moderate hypoglycaemia rate with insulin degludec versus insulin glargine U100.

In the DEVOTE and SWITCH 2 trials, insulin degludec 100 units/mL (degludec) was superior to insulin glargine 100 units/mL (glargine U100) with respect to the rates of severe (DEVOTE; across trial) and overall symptomatic (SWITCH 2; during the maintenance period of the trial) hypoglycaemia in individuals with type 2 diabetes. In this post hoc analysis, data from 7635 individuals from DEVOTE and 720 individuals from SWITCH 2 were analysed by subgroups of diabetes duration at baseline (<10, ≥10–<15, ≥15–<20 and ≥20 years) using prespecified models from both trials. There was a trend towards lower rates of hypoglycaemia with degludec versus glargine U100 across all diabetes duration subgroups in both trials, with the difference being statistically significant in some subgroups in DEVOTE and SWITCH 2. Overall, however, no significant interaction was observed between diabetes duration and treatment (DEVOTE interaction, P = .496; SWITCH 2 interaction, P = .144). Therefore, in this post hoc analysis of DEVOTE and SWITCH 2, diabetes duration did not appear to affect the reduction in rates of hypoglycaemia observed with degludec compared with glargine U100.

The differences between insulin glargine U300 and insulin degludec U100 in impact on the glycaemic variability, arterial stiffness and the lipid profiles in insulin na\xefve patients suffering from type two diabetes mellitus \u2013 outcomes from cross\u2010over open-label randomized trial

Background and aimsDiabetes mellitus type two is one of the major cardiovascular risk factors. Treatment of diabetes can reduce this risk, but the treatment options differ a lot in their risk-reducing capabilities. We compared the impact of insulin degludec (IDeg-100) and insulin glargine U300 (IGlar-300) on cardiovascular risk parameters - glycaemic variability (GV), arterial stiffness and lipid parameters - in insulin naive patients with DMT2.MethodsTo 23 individuals who previously had uncontrolled DMT2 on two or more oral antidiabetic drugs, IGlar-300 and IDeg-100 were applied for 12 weeks and then switched in a cross over design manner. Prior and after of each insulin phase, we analysed biochemical parameters,7-point SMBG profile over three days and arterial stiffness which was assessed indirectly by measuring the augmentation index (AIx) on the principles of applanation tonometry.ResultsThere were no significant differences between IGlar-300 and IDeg-100 regarding reduction of mean glucose values and coefficient of variation (CV). Both insulins insignificantly reduced AIx for standardised pulse of 75 beats/min and without differences between them. IGlar-300 and IDeg-100 reduced triglycerides and increased HDL with no significant difference between the two insulins. IGlar-300 increased the total cholesterol level and IDeg-100 decreased total cholesterol, but without statistically significant difference. IGlar-300 increased LDL level by 0.508 mmol/L and IDeg-100 decreased LDL by 0.217 mmol/L, with statistically significant difference (p = 0.0215).ConclusionsThis study did not show significant difference between IGlar-300 and IDeg-100 regarding glycaemic parameters and augmentation index using the same dose of 0.2 IU/kg for both insulins, but it has revealed possible differences in impact on lipid profile.Trial RegistrationClinicaltrials.gov, NCT04692415. Retrospectively registered on December 31th 2020.

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...

Switching to Once-Weekly Insulin Icodec Versus Once-Daily Insulin Glargine U100 in Type 2 Diabetes Inadequately Controlled on Daily Basal Insulin: A Phase 2 Randomized Controlled Trial

OBJECTIVEInsulin icodec (icodec) is a novel once-weekly basal insulin analog. This trial investigated two approaches for switching to icodec versus once-daily insulin glargine 100 units/mL (IGlar U100) in people with type 2 diabetes receiving daily basal insulin and one or more oral glucose-lowering medications.RESEARCH DESIGN AND METHODSThis multicenter, open-label, treat-to-target phase 2 trial randomized (1:1:1) eligible basal insulin–treated (total daily dose 10–50 units) people with type 2 diabetes (HbA1c 7.0–10.0% [53.0–85.8 mmol/mol]) to icodec with an initial 100% loading dose (in which only the first dose was doubled [icodec LD]), icodec with no loading dose (icodec NLD), or IGlar U100 for 16 weeks. Primary end point was percent time in range (TIR; 3.9–10.0 mmol/L [70–180 mg/dL]) during weeks 15 and 16, measured using continuous glucose monitoring. Key secondary end points included HbA1c, adverse events (AEs), and hypoglycemia.RESULTSEstimated mean TIR during weeks 15 and 16 was 72.9% (icodec LD; n = 54), 66.0% (icodec NLD; n = 50), and 65.0% (IGlar U100; n = 50), with a statistically significant difference favoring icodec LD versus IGlar U100 (7.9%-points [95% CI 1.8–13.9]). Mean HbA1c reduced from 7.9% (62.8 mmol/mol) at baseline to 7.1% (54.4 mmol/mol icodec LD) and 7.4% (57.6 mmol/mol icodec NLD and IGlar U100); incidences and rates of AEs and hypoglycemic episodes were comparable.CONCLUSIONSSwitching from daily basal insulin to once-weekly icodec was well tolerated and provided effective glycemic control. Loading dose use when switching to once-weekly icodec significantly increased percent TIR during weeks 15 and 16 versus once-daily IGlar U100, without increasing hypoglycemia risk.

Effect of basal insulin therapy with glargine U300 versus basal bolus insulin therapy in hospitalized patients with type 2 diabetes. Real-world study from India

Background. Basal-bolus insulin therapy is the most widely accepted method of glycemic control in non-critically ill patients with T2DM. In this regimen glargine U100 is the most commonly used basal insulin. American Diabetes Association recommends either basal or basal bolus therapy for patients with type 2 diabetes mellitus admitted in general medical and surgical ward with ideal glycemic target ranging between 140–180 mg/dL by estimating four or 6 hourly capillary blood glucose per day. Insulin glargine U300 is a second generation long acting insulin analogue, which has a prolonged pharmacokinetic /pharmacodynamic profile compared to insulin glargine U100 resulting in glucose lowering activity exceeding 24 hours. Aim. To assess the efficacy and safety of basal insulin regimen (glargine U300) compared to a basal-bolus insulin regimen in patients with type 2 diabetes. Methods. A prospective single centred parallel group study comparing the efficacy and safety of basal insulin regimen with basal-bolus insulin regimen. A total of 60 patients with type 2 diabetes mellitus admitted in general medical and surgical ward for elective surgery and medical emergency were randomized to either of the two regimens. The baseline glycaemic parameters were assessed by capillary blood glucose testing thrice before meal and at bedtime with a target capillary blood glucose (CBG) between 140–180 mg/dL. All pa-tients were followed up for seven days. Results. The number of CBG readings within the target range were higher in basal insulin monotherapy (glargine U300) compared to basal-bolus regimen using (glargine U100 and regular human insulin) which was statistically significant. The incidence of hypoglycaemia was lower in the basal insulin regimen. Fewer units of insulin were required in the basal insulin regimen with lower glycaemic variability as compared to basal-bolus regimen. Conclusion. Glargine U 300 monotherapy as a basal insulin is non-inferior to basal- bolus therapy in non-critically ill hospitalised patients in glycaemic control, with fewer incidences of hypoglycaemia, less amount of insulin requirement to achieve target capillary blood glucose level and lower glycaemic variability.

Hospitalization costs with degludec versus glargine U100 for patients with type 2 diabetes at high cardiovascular risk: Canadian costs applied to SAEs from a randomized outcomes trial

Objectives The present cost–consequence analysis compared estimated hospitalization costs in a Canadian setting with insulin degludec (degludec) versus insulin glargine 100 units/mL (glargine U100) in patients with type 2 diabetes (T2D) at high cardiovascular (CV) risk. Methods Medical terms were mapped across the different vocabularies, in order to assign unit costs from eligible hospital abstracts in Canadian Institute for Health Information data (International Statistical Classification of Diseases and Related Health Problems, 10th Revision, Canada) to serious adverse events (SAEs; Medical Dictionary for Regulatory Activities) from the randomized DEVOTE trial comparing the two insulins degludec and glargine. Mean annual costs of SAE-related hospitalizations were estimated by treatment, the cost difference (degludec − glargine U100) was bootstrapped to compute confidence intervals (CIs) and p-values, and the cost ratio (degludec/glargine U100) was estimated using a Tweedie distribution. Results The mean annual cost per patient for SAE-related hospitalizations was 4,074 CAD with degludec and 4,569 CAD with glargine U100 (cost difference: −495, 95% confidence interval [CI]: −966; −24, p = .039), for a cost ratio of 0.89 (95% CI: 0.81; 0.98, p = .016). Overall, cost ratios from sensitivity analyses varying individual methodological assumptions were consistent with the main analysis. Of the system organ classes from DEVOTE SAEs, cardiac disorders were the largest contributor to the costs savings with degludec versus glargine U100. Conclusions In patients with T2D at high CV risk, our findings suggest that there are likely to be lower hospitalization costs with degludec versus glargine U100 based on the SAEs observed in DEVOTE and in a Canadian setting.

Clinical research of insulin glargine U300 in type 1 diabetes mellitus patients with frequent hypoglycaemia: real-world experience.

IntroductionWe aimed to see whether insulin glargine U300 can provide better blood glucose control while reducing hypoglycaemia in a more homogeneous population compared to previous studies.Material and methodsThe retrospective study included type 1 diabetes mellitus (T1DM) patients with frequent hypoglycaemia. For evaluation of fasting blood glucose, haemoglobin glycated (HbA1c) and weight at 6 months and 12 months (final), observation windows of 120–240 days (4–8 months) and 240–480 days (9–16 months) after insulin glargine U300 initiation, respectively, were permitted. Mean follow-up time was 12 months. Hypoglycaemia was defined as blood glucose level < 70 mg/dl, either symptomatic or asymptomatic, measured in hospital or at home.ResultsForty-four patients were included in the study, and 35 patients completed the study – 20 (57.1%) females and 15 (42.9%) males, with a mean age of 24.1 ±6.6 years. Mean body mass index was 24.4 ±7.4 kg/m2. A significant decrease was not found between baseline and HbA1c values at 6 months (p = 0.199), but a significant decrease was found in the final period (between 9–16 months) (p = 0.025). Hypoglycaemic events occurred in all patients (100%) before using insulin glargine U300, while the incidence of hypoglycaemic events gradually decreased to 74.3%, 68.6%, and 68.6% between months 1–3, 3–6, and 6–9, respectively. Of the 26 patients who declared their level of satisfaction, 23 (88.5%) were satisfied, 2 (7.7%) indicated that there was no significant difference, and 1 (3.8%) patient was unsatisfied.ConclusionsOver 9–16 months of follow-up, insulin glargine U300 led to a significant reduction not only of HbA1c levels but also of the frequency of hypoglycaemia, and also yielded high satisfaction rates.

Advances in newer basal and bolus insulins: impact on type 1 diabetes.

Insulin administration is vitally important to maintain a good glycaemic control in people with type 1 diabetes mellitus (T1DM). The purpose of this review is to give a clinically relevant overview of the newer basal and bolus insulin analogues and to highlight their practicalities of use and advantages in specific categories of patients with T1DM. Second-generation rapid-acting insulin analogues (i.e. faster insulin aspart and ultrarapid-acting lispro) have shown to be safe, efficient and superior in controlling postprandial plasma glucose levels without an increase in hypoglycaemia. The newest basal insulin analogues, insulin glargine U300 and degludec, have proven to be efficient in reducing hypoglycaemic events due to a more stable action profile. The second-generation rapid-acting and basal insulin analogues approach better the desired physiological insulin pattern of the beta cell. Due to a faster absorption, it is possible to inject the prandial insulin analogues more closely or even after meals without compromising postprandial glucose control. Due to more stable release patterns, basal insulins now have more reliable and longer profiles, covering basal insulin demands in a superior way, leading to a better glycaemic control with less hypoglycaemia (especially nocturnal events) and an improved quality of life.

Once-Weekly Insulin for Type 2 Diabetes without Previous Insulin Treatment

BackgroundIt is thought that a reduction in the frequency of basal insulin injections might facilitate treatment acceptance and adherence among patients with type 2 diabetes. Insulin icodec is a basal insulin analogue designed for once-weekly administration that is in development for the treatment of diabetes.MethodsWe conducted a 26-week, randomized, double-blind, double-dummy, phase 2 trial to investigate the efficacy and safety of once-weekly insulin icodec as compared with once-daily insulin glargine U100 in patients who had not previously received long-term insulin treatment and whose type 2 diabetes was inadequately controlled (glycated hemoglobin level, 7.0 to 9.5%) while taking metformin with or without a dipeptidyl peptidase 4 inhibitor. The primary end point was the change in glycated hemoglobin level from baseline to week 26. Safety end points, including episodes of hypoglycemia and insulin-related adverse events, were also evaluated.ResultsA total of 247 participants were randomly assigned (1:1) to receive icodec or glargine. Baseline characteristics were similar in the two groups; the mean baseline glycated hemoglobin level was 8.09% in the icodec group and 7.96% in the glargine group. The estimated mean change from baseline in the glycated hemoglobin level was −1.33 percentage points in the icodec group and −1.15 percentage points in the glargine group, to estimated means of 6.69% and 6.87%, respectively, at week 26; the estimated between-group difference in the change from baseline was −0.18 percentage points (95% CI, –0.38 to 0.02, P=0.08). The observed rates of hypoglycemia with severity of level 2 (blood glucose level, <54 mg per deciliter) or level 3 (severe cognitive impairment) were low (icodec group, 0.53 events per patient-year; glargine group, 0.46 events per patient-year; estimated rate ratio, 1.09; 95% CI, 0.45 to 2.65). There was no between-group difference in insulin-related key adverse events, and rates of hypersensitivity and injection-site reactions were low. Most adverse events were mild, and no serious events were deemed to be related to the trial medications.ConclusionsOnce-weekly treatment with insulin icodec had glucose-lowering efficacy and a safety profile similar to those of once-daily insulin glargine U100 in patients with type 2 diabetes. (Funded by Novo Nordisk; NN1436-4383 ClinicalTrials.gov number, NCT03751657.)

(Ultra-)long-acting insulin analogues versus NPH insulin (human isophane insulin) for adults with type 2 diabetes mellitus.

(Ultra-)long-acting insulin analogues versus NPH insulin (human isophane insulin) for adults with type 2 diabetes mellitus.

Risk factors for kidney disorders in patients with type 2 diabetes at high cardiovascular risk: An exploratory analysis (DEVOTE 12).

Aim:To investigate risk factors associated with kidney disorders in patients with type 2 diabetes (T2D) at high cardiovascular (CV) risk.Methods:In DEVOTE, a cardiovascular outcomes trial, 7637 patients were randomised to insulin degludec (degludec) or insulin glargine 100 units/mL (glargine U100), with standard of care. In these exploratory post hoc analyses, serious adverse event reports were searched using Standardised MedDRA® Queries related to chronic kidney disease (CKD) or acute kidney injury (AKI). Baseline predictors of CKD, AKI and change in estimated glomerular filtration rate (eGFR) were identified using stepwise selection and Cox or linear regression.Results:Over 2 years, eGFR (mL/min/1.73 m2) decline was small and similar between treatments (degludec: 2.70; glargine U100: 2.92). Overall, 97 and 208 patients experienced CKD and AKI events, respectively. A history of heart failure was a risk factor for CKD (hazard ratio [HR] 1.97 [95% confidence interval [CI] 1.41; 2.75]) and AKI (HR 2.28 [95% CI 1.64; 3.17]). A history of hepatic impairment was a significant predictor of CKD (HR 3.28 [95% CI 2.12; 5.07]) and change in eGFR (estimate: −8.59 [95% CI −10.20; −7.00]).Conclusion:Our findings indicate that traditional, non-modifiable risk factors for kidney disorders apply to insulin-treated patients with T2D at high CV risk.Trial registration:NCT01959529 (ClinicalTrials.gov).

Efficacy and Safety of Tofogliflozin and Ipragliflozin for Patients with Type-2 Diabetes: A Randomized Crossover Study by Flash Glucose Monitoring.

IntroductionSodium-glucose cotransporter 2 (SGLT2) inhibitors promote urinary glucose excretion. However, the differences in the effects of various SGLT2 inhibitors are unknown. We used flash glucose monitoring (FGM) to identify the differences between tofogliflozin and ipragliflozin in terms of efficacy in reducing glycemic variability and mitigate hypoglycemia risk.MethodsIn this crossover study, 24 patients with type-2 diabetes mellitus (T2DM) receiving insulin glargine U300 therapy were randomly allocated to tofogliflozin and ipragliflozin or ipragliflozin and tofogliflozin group. Glycemic variability and hypoglycemia were compared using to the 3-day FGM data per treatment period.ResultsGlucose level 2 h after each meal was significantly lower with tofogliflozin administration than with ipragliflozin administration. Time below the target glucose range after tofogliflozin administration was significantly lower than that after ipragliflozin administration (2.1% ± 4.4% vs. 8.7% ± 11.7%). The 24-h standard deviation of glucose level, mean amplitude of glycemic excursion, and mean percent time with nocturnal hypoglycemia after tofogliflozin administration were significantly lower than those after ipragliflozin administration.ConclusionsTofogliflozin was more effective and safer than ipragliflozin in reducing glycemic variability and mitigating hypoglycemia risk in patients with T2DM treated with insulin glargine U300.Trial RegistrationThis trial was registered at the University Hospital Medical Information Network Clinical Trial Registry (no. UMIN000037158).Electronic MaterialThe online version of this article (10.1007/s13300-020-00940-9) contains supplementary material, which is available to authorized users.

65 - Randomized Comparison of Initiating Insulin Glargine or Iglarlixi in South Asian Canadians With Type 2 Diabetes: VARIATION 2 SA Trial

To compare initiation of a fixed-ratio combination of glargine-lixisenatide (iGlarLixi) and insulin glargine U100 (iGlar), exclusively in South Asian origin Canadians.

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.

Real-world cost-effectiveness of insulin degludec in type 1 and type 2 diabetes mellitus from a Swedish 1-year and long-term perspective

Background and aims The ReFLeCT study demonstrated that switching to insulin degludec from other basal insulins was associated with reductions in glycated hemoglobin and hypoglycemic events in type 1 (T1D) and type 2 diabetes (T2D), and reductions in insulin doses in T1D. The aim of the present analysis was to assess the short- and long-term cost-effectiveness of switching to insulin degludec in Sweden. Methods Short-term outcomes were evaluated over 1 year in a Microsoft Excel model, while long-term outcomes were projected over patient lifetimes using the IQVIA CORE Diabetes Model. Cohort characteristics and treatment effects were sourced from the ReFLeCT study. Costs (in 2018 Swedish krona [SEK]) encompassed direct medical expenditure and indirect costs from loss of workplace productivity. In the long-term analyses, patients were assumed to receive insulin degludec or continue prior insulin therapy (primarily insulin glargine U100) for 5 years, before all patients intensified to once-daily degludec and mealtime aspart. Results Switching to insulin degludec was associated with improved quality-adjusted life expectancy of 0.04 and 0.02 quality-adjusted life years (QALYs) over 1 year, and 0.16 and 0.08 QALYs over patient lifetimes, in T1D and T2D. Combined costs in T1D and T2D were estimated to be SEK 1,249 lower and SEK 1,181 higher over the short-term, and SEK 157,258 and SEK 2,114 lower over the long-term. Benefits were due to lower insulin doses in T1D, reduced rates of hypoglycemia, and lower incidences of diabetes-related complications. Insulin degludec was associated with an incremental cost-effectiveness ratio of SEK 64,298 per QALY gained for T2D over 1 year and considered dominant for T1D and T2D in all other comparisons. Conclusions Insulin degludec was projected to be cost-effective or dominant versus other basal insulins for the treatment of T1D and T2D in Sweden.