An exploratory analysis of the cost-effectiveness of insulin glargine 300 units/mL versus insulin glargine 100 units/mL over a lifetime horizon using the BRAVO diabetes model.

BACKGROUND: This analysis assessed the cost-effectiveness of insulin glargine 300 units/mL (Gla-300) versus insulin glargine 100 units/mL (Gla-100) in insulin-naïve adults with type 2 diabetes (T2D) inadequately controlled with oral antidiabetic drugs (OADs). METHODS: Costs and outcomes for Gla-300 versus Gla-100 from a US healthcare payer perspective were assessed using the BRAVO diabetes model. Baseline clinical data were derived from EDITION-3, a 12-month randomized controlled trial comparing Gla-300 with Gla-100 in insulin-naïve adults with inadequately controlled T2D on OADs. Treatment costs were calculated based on doses observed in EDITION-3 and 2020 US net prices, while costs for complications were based on published literature. Lifetime costs ($US) and quality-adjusted life-years (QALYs) were predicted and used to calculate incremental cost-effectiveness ratio (ICER) estimates; extensive scenario and sensitivity analyses were conducted. RESULTS: Lifetime medical costs were estimated to be $353,441 and $352,858 for individuals receiving Gla-300 and Gla-100 respectively; insulin costs were $52,613 and $50,818. Gla-300 was associated with a gain of 8.97 QALYs and 21.12 life-years, while Gla-100 was associated with a gain of 8.89 QALYs and 21.07 life-years. This resulted in an ICER of $7522/QALY gained for Gla-300 versus Gla-100. Thus, Gla-300 was cost-effective versus Gla-100 based on a willingness-to-pay threshold of $50,000/QALY. Compared with Gla-100, Gla-300 provided a net monetary benefit of $3290. Scenario and sensitivity analyses confirmed the robustness of the base case. CONCLUSION: Gla-300 may be a cost-effective treatment option versus Gla-100 over a lifetime horizon for insulin-naïve people in the United States with T2D inadequately controlled on OADs.

Immunogenicity, efficacy, and safety of biosimilar insulin glargine (Gan & Lee glargine) compared with originator insulin glargine (Lantus®) in patients with type 2 diabetes after 26 weeks' treatment: A randomized open label study.

AIM: To evaluate the equivalence of immunogenicity, safety and efficacy of Gan & Lee (GL) Glargine (Basalin®; Gan & Lee Pharmaceutical) with that of the reference product (Lantus®) in adult participants with type 2 diabetes mellitus. METHODS: This was a phase 3, multicenter, open-label, equivalence trial conducted across 57 sites. In total, 567 participants with type 2 diabetes mellitus were randomized in a 1:1 ratio to undergo treatment with either GL Glargine or Lantus® for 26 weeks. The primary endpoint was the proportion of participants in each treatment arm who manifested treatment-induced anti-insulin antibodies (AIA). Secondary endpoints included efficacy and safety metrics, changes in glycated haemoglobin levels, and a comparative assessment of adverse events. Results were analysed using an equivalence test comparing the limits of the 90% confidence interval (CI) for treatment-induced AIA development to the prespecified margins. RESULTS: The percentages of participants positive for treatment-induced glycated haemoglobin by week 26 were similar between the GL Glargine (19.2%) and Lantus® (21.3%) treatment groups, with a treatment difference of -2.1 percentage points and a 90% CI (-7.6%, 3.5%) (predefined similarity margins: -10.7%, 10.7%). The difference in glycated haemoglobin was -0.08% (90% CI, -0.23, 0.06). The overall percentage of participants with any treatment-emergent adverse events was similar between the GL Glargine (80.1%) and Lantus® (81.6%) treatment groups. CONCLUSIONS: GL Glargine was similar to Lantus® in terms of immunogenicity, efficacy, and safety, based on the current study.

Real-world effectiveness and safety of insulin glargine 100 U/mL plus lixisenatide in adults with type 2 diabetes: An international, multicentre, 12-month, prospective observational study.

AIM: To assess the impact of insulin glargine (100 U/mL) and lixisenatide (iGlarLixi) fixed-ratio combination therapy on the overall management of glycaemia in patients with type 2 diabetes (T2D), previously inadequately controlled with oral antidiabetic drugs ± basal insulin or glucagon-like peptide-1 receptor agonists (GLP-1 RAs). MATERIALS AND METHODS: This 12-month, international, multicentre, prospective, observational study included patients (age ≥ 18 years) with T2D who had initiated iGlarLixi within 1 month prior to study inclusion. Data were collected at study inclusion, month 3, month 6 and month 12 from patient diaries, self-measured plasma glucose, and questionnaires. The primary endpoint was change in HbA1c from baseline to month 6. RESULTS: Of the 737 eligible participants (mean age: 57.8 [standard deviation: 11.2] years; male: 49%), 685 had baseline and post-baseline HbA1c data available. The least squares mean change in HbA1c from baseline to month 6 was -1.4% (standard error [95% confidence interval (CI)]: 0.05 [-1.5, -1.3]). The absolute change from baseline at month 12 was -1.7% ± 1.9% (95% CI: -1.9, -1.5). There were 72 hypoglycaemia events reported during the study period, with a very low incidence of severe hypoglycaemia (two participants [rate: 0.003 events per patient-year]). CONCLUSIONS: This real-world observational study shows that initiation of iGlarLixi in people with T2D inadequately controlled on oral antidiabetic drugs ± basal insulin or GLP-1 RAs improves glycaemic control with a low incidence of hypoglycaemia.

Immunogenicity, Efficacy, and Safety of Biosimilar Insulin Glargine (Gan & Lee Glargine) Compared With Originator Insulin Glargine (Lantus) in Patients With Type 1 Diabetes After 26 Weeks Treatment.

OBJECTIVE: To compare the immunogenicity, safety, and efficacy of Gan & Lee insulin glargine (GL Glargine) with that of the originator insulin glargine (Lantus) in patients with type 1 diabetes mellitus (T1DM). METHODS: This was a phase 3, multicenter, randomized, open-label, equivalence study. Five hundred seventy-six subjects with T1DM were randomized 1:1 to receive either GL Glargine or Lantus treatment for 26 weeks. The primary end point was the percentage of subjects in each treatment group who developed treatment-induced anti-insulin antibody after baseline and up to visit week 26, which was evaluated using a country-adjusted logistic regression model. The study also compared the changes in glycated hemoglobin, and adverse events including hypoglycemia. RESULTS: The percentage of subjects positive for treatment-induced anti-insulin antibody by Week 26 was 25.8% in the GL Glargine treatment group and 25.3% in the Lantus treatment group, with a 90% confidence interval (-5.4, 6.5) of the difference in proportions that fell completely between the similarity margins (-11.3, 11.3). The least squares mean difference between treatment groups for changes in glycated hemoglobin was -0.08 (90% confidence interval: -0.23, 0.06), and the other immunogenicity and safety profiles were comparable. CONCLUSION: GL Glargine demonstrated similar immunogenicity, efficacy, and safety compared to Lantus over 26 weeks in patients with T1DM.

Hypoglycaemia frequency and physiological response after double or triple doses of once-weekly insulin icodec vs once-daily insulin glargine U100 in type 2 diabetes: a randomised crossover trial.

AIMS/HYPOTHESIS: This study compared the frequency of hypoglycaemia, time to hypoglycaemia and recovery from hypoglycaemia after double or triple doses of once-weekly insulin icodec vs once-daily insulin glargine U100. Furthermore, the symptomatic and counterregulatory responses to hypoglycaemia were compared between icodec and glargine U100 treatment. METHODS: In a randomised, single-centre (Department of Internal Medicine, Division of Endocrinology and Diabetology, Medical University of Graz, Graz, Austria), open-label, two-period crossover trial, individuals with type 2 diabetes (age 18-72 years, BMI 18.5-37.9 kg/m2, HbA1c ≤75 mmol/mol [≤9.0%]) treated with basal insulin with or without oral glucose-lowering drugs received once-weekly icodec (for 6 weeks) and once-daily glargine U100 (for 11 days). Total weekly doses were equimolar based on individual titration of daily glargine U100 during the run-in period (target fasting plasma glucose [PG]: 4.4-7.2 mmol/l). Randomisation was carried out by assigning a randomisation number to each participant in ascending order, which encoded to one of two treatment sequences via a randomisation list prepared prior to the start of the trial. At steady state, double and triple doses of icodec and glargine U100 were administered followed by hypoglycaemia induction: first, euglycaemia was maintained at 5.5 mmol/l by variable i.v. infusion of glucose; glucose infusion was then terminated, allowing PG to decrease to no less than 2.5 mmol/l (target PGnadir). The PGnadir was maintained for 15 min. Euglycaemia was restored by constant i.v. glucose (5.5 mg kg-1 min-1). Hypoglycaemic symptoms score (HSS), counterregulatory hormones, vital signs and cognitive function were assessed at predefined PG levels towards the PGnadir. RESULTS: Hypoglycaemia induction was initiated in 43 and 42 participants after double dose of icodec and glargine U100, respectively, and in 38 and 40 participants after triple doses, respectively. Clinically significant hypoglycaemia, defined as PGnadir <3.0 mmol/l, occurred in comparable proportions of individuals treated with icodec vs glargine U100 after double (17 [39.5%] vs 15 [35.7%]; p=0.63) and triple (20 [52.6%] vs 28 [70.0%]; p=0.14) doses. No statistically significant treatment differences were observed in the time to decline from PG values of 5.5 mmol/l to 3.0 mmol/l (2.9-4.5 h after double dose and 2.2-2.4 h after triple dose of the insulin products). The proportion of participants with PGnadir ≤2.5 mmol/l was comparable between treatments after double dose (2 [4.7%] for icodec vs 3 [7.1%] for glargine U100; p=0.63) but higher for glargine U100 after triple dose (1 [2.6%] vs 10 [25.0%]; p=0.03). Recovery from hypoglycaemia by constant i.v. glucose infusion took <30 min for all treatments. Analyses of the physiological response to hypoglycaemia only included data from participants with PGnadir <3.0 mmol/l and/or the presence of hypoglycaemic symptoms; in total 20 (46.5%) and 19 (45.2%) individuals were included after a double dose of icodec and glargine U100, respectively, and 20 (52.6%) and 29 (72.5%) individuals were included after a triple dose of icodec and glargine U100, respectively. All counterregulatory hormones (glucagon, adrenaline [epinephrine], noradrenaline [norepinephrine], cortisol and growth hormone) increased during hypoglycaemia induction with both insulin products at both doses. Following triple doses, the hormone response was greater with icodec vs glargine U100 for adrenaline at PG3.0 mmol/l (treatment ratio 2.54 [95% CI 1.69, 3.82]; p<0.001), and cortisol at PG3.0 mmol/l (treatment ratio 1.64 [95% CI 1.13, 2.38]; p=0.01) and PGnadir (treatment ratio 1.80 [95% CI 1.09, 2.97]; p=0.02). There were no statistically significant treatment differences in the HSS, vital signs and cognitive function. CONCLUSIONS/INTERPRETATION: Double or triple doses of once-weekly icodec lead to a similar risk of hypoglycaemia compared with double or triple doses of once-daily glargine U100. During hypoglycaemia, comparable symptomatic and moderately greater endocrine responses are elicited by icodec vs glargine U100. TRIAL REGISTRATION: ClinicalTrials.gov NCT03945656. FUNDING: This study was funded by Novo Nordisk A/S.

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

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

Cost-effectiveness analysis of once-daily insulin glargine 300 U/mL versus insulin degludec 100 U/mL using the BRAVO diabetes model.

AIMS: A cost-effectiveness analysis was conducted to compare insulin glargine 300 U/mL (Gla-300) versus insulin degludec 100 U/mL (IDeg-100) in insulin-naïve adults with type 2 diabetes (T2D) sub-optimally controlled with oral anti-diabetic drugs (OADs). METHODS: The BRAVO diabetes model was used to assess costs and outcomes for once-daily Gla-300 versus once-daily IDeg-100 from a US healthcare sector perspective. Baseline clinical data were based on BRIGHT, a 24-week, non-inferiority, randomised control trial comparing Gla-300 and IDeg-100 in adults with T2D sub-optimally controlled with OADs (with or without glucagon-like peptide-1 receptor agonists). Treatment costs were based on doses observed in BRIGHT as well as net prices. Costs associated with complications were based on published literature. Lifetime costs (US$) and quality-adjusted life-years (QALYs) were predicted and used to calculate incremental cost-effectiveness ratio estimates; extensive scenario and sensitivity analyses were conducted. RESULTS: Overall lifetime medical costs were estimated to be $327,904 and $330,154 for people receiving Gla-300 and IDeg-100, respectively; insulin costs were $43,477 and $44,367, respectively. People receiving Gla-300 gained 8.024 QALYs and 18.55 life-years, while people receiving IDeg-100 gained 7.997 QALYs and 18.52 life-years. Because Gla-300 was associated with a cost-saving of $2250 and 0.027 additional QALYs, it was considered to be dominant compared with IDeg-100. Results of the scenario and sensitivity analyses confirmed the robustness of the base case results. CONCLUSION: Gla-300 was the dominant treatment option compared with IDeg-100 based on the willingness-to-pay threshold of $50,000/QALY. Results remained robust against a wide range of alternative assumptions on key parameters.

Comparative efficacy and safety of Gla-300 versus IDegAsp in insulin-naïve people with type 2 diabetes mellitus uncontrolled on oral anti-diabetics.

AIM: To compare the efficacy and safety of insulin glargine-300 once daily (Gla-300) with insulin degludec/aspart (IDegAsp) once daily in patients with type 2 diabetes (T2D) inadequately controlled on oral anti-diabetic drugs (OADs). MATERIALS AND METHODS: A systematic literature review of randomized controlled trials was followed by an indirect treatment comparison of studies involving insulin naïve adults, inadequately controlled [glycated haemoglobin (HbA1c) ≥7.0%] on OADs, who received Gla-300 or IDegAsp once daily. Outcomes of interest were change in HbA1c, blood glucose, weight and insulin dose, as well as incidence and event rate of hypoglycaemia and other adverse events. RESULTS: Four trials with broadly similar baseline patient characteristics were included in the meta-analyses and indirect treatment comparison. At 24-28 weeks, the indirect comparison of Gla-300 to IDegAsp once daily estimated no statistically significant difference for change in HbA1c (%) from baseline [mean difference of 0.10% (95% CI: -0.20, 0.39; p = .52)]; a statistically significant mean difference of -1.31 kg (95% CI: -1.97, -0.65; p < .05) for change in body weight from baseline; statistically significant odds ratios of 0.62 (95% CI: 0.41, 0.93; p < .05) for incidence of any hypoglycaemia; and 0.47 (95% CI: 0.25, 0.87; p < .05) for incidence of anytime confirmed hypoglycaemia (plasma glucose <3.0-3.1 mmol/L). No significant differences were observed for insulin dose and adverse events. CONCLUSION: In insulin-naïve patients with T2D inadequately controlled on OADs, commencing Gla-300 shows a comparable HbA1c reduction, but with significantly less weight gain and a lower incidence of any and confirmed hypoglycaemia compared with commencing IDegAsp.

iGlarLixi provides a higher derived time-in-range versus insulin glargine 100 U/mL or lixisenatide in Asian Pacific people with type 2 diabetes: A post hoc analysis.

AIM: To evaluate the efficacy of iGlarLixi in the Asian Pacific (AP) population with type 2 diabetes (T2D) using derived time-in-ranges calculated from seven-point self-measured blood glucose. METHODS: Two phase III trials were analysed. LixiLan-O-AP was performed in insulin-naive T2D patients (n = 878) randomized to iGlarLixi, glargine 100 units/mL (iGlar) or lixisenatide (Lixi). LixiLan-L-CN was performed in insulin-treated T2D patients (n = 426) randomized to iGlarLixi or iGlar. Changes in derived time-in-ranges from baseline to end-of-treatment (EOT) and estimated treatment differences (ETDs) were analysed. The proportions of patients achieving 70% or higher derived time-in-range (dTIR), 5% or higher dTIR improvement, and the composite triple target (≥ 70% dTIR, < 4% derived time-below-the-range [dTBR] and < 25% derived time-above-the-range [dTAR]) were calculated. RESULTS: The changes from baseline to EOT in dTIR with iGlarLixi were greater versus iGlar (ETD1 : 11.45% [95% CI, 7.66% to 15.24%]) or Lixi (ETD2 : 20.54% [95% CI, 15.74% to 25.33%]) in LixiLan-O-AP, and versus iGlar (ETD: 16.59% [95% CI, 12.09% to 21.08%]) in LixiLan-L-CN. In LixiLan-O-AP, the proportions of patients achieving 70% or higher dTIR or 5% or higher dTIR improvement at EOT with iGlarLixi were 77.5% and 77.8%, respectively, higher than with iGlar (61.1% and 75.3%) or Lixi (47.0% and 53.0%). In LixiLan-L-CN, the proportions of patients achieving 70% or higher dTIR or 5% or higher dTIR improvement at EOT were 71.4% and 59.8% with iGlarLixi, greater than with iGlar (45.4% and 39.5%). More patients achieved the triple target with iGlarLixi compared with iGlar or Lixi. CONCLUSION: iGlarLixi achieved greater improvements in dTIR parameters versus iGlar or Lixi in insulin-naïve and insulin-experienced AP people with T2D.

Pharmacokinetic and pharmacodynamic bioequivalence of Gan & Lee insulin analogues aspart (rapilin®), lispro (prandilin®) and glargine (basalin®) with EU- und US-sourced reference insulins.

AIM: For the successful approval and clinical prescription of insulin biosimilars, it is essential to show pharmacokinetic (PK) and pharmacodynamic (PD) bioequivalence to the respective reference products sourced from the European Union and the United States. METHODS: Three phase 1, randomized, double-blind, three-period crossover trials compared single doses of the proposed biosimilar insulin analogues aspart (GL-Asp, n = 36), lispro (GL-Lis, n = 38) and glargine (GL-Gla, n = 113), all manufactured by Gan & Lee pharmaceuticals, to the respective EU- and US-reference products in healthy male participants (GL-Asp and GL-Lis) or people with type 1 diabetes (GL-Gla). Study participants received 0.2 U/kg (aspart and lispro) or 0.5 U/kg (glargine) of each treatment under automated euglycaemic clamp conditions. The clamp duration was 12 h (aspart and lispro) or 30 h (glargine). Primary PK endpoints were the total area under the PK curves (AUCins.total ) and maximum insulin concentrations (Cins.max ). Primary PD endpoints were the total area under the glucose infusion rate curve (AUCGIR.total ) and maximum glucose infusion rate (GIRmax ). RESULTS: Bioequivalence to both EU- and US-reference products were shown for all three GL insulins. Least squares mean ratios for the primary PK/PD endpoints were close to 100%, and both 90% and 95% confidence intervals were within 80%-125% in all three studies. There were no noticeable differences in the safety profiles between test and reference insulins, and no serious adverse events were reported for the GL insulins. CONCLUSION: GL-Asp, GL-Lis and GL-Gla are bioequivalent to their EU- and US-reference products.

Efficacy and safety of basal-first titration order in individuals with type 2 diabetes receiving short-term intensive insulin therapy: An exploratory analysis of BEYOND V.

AIMS: To present the results of an exploratory analysis of the BEYOND V study in which Chinese individuals with uncontrolled type 2 diabetes (T2D) received short-term intensive insulin therapy (SIIT) during study run-in (prior to randomization) using a basal-first insulin titration method. MATERIALS AND METHODS: This was exclusively an exploratory analysis of the 7- to 10-day run-in period of BEYOND V. Participants were hospitalized and had oral therapies withdrawn (except metformin). They received SIIT with once-daily insulin glargine and three-times-daily premeal insulin glulisine, titrated daily from a total starting dose of 0.4 to 0.5 units/kg/d, first adjusting insulin glargine to achieve fasting blood glucose (FBG) of 4.4 to 6.1 mmol/L (79 to 119 mg/dL), then insulin glulisine to achieve pre-meal blood glucose of 4.4 to 6.1 mmol/L. Key outcomes were the proportions of participants achieving FBG and 2-hour postprandial blood glucose (PBG) targets. RESULTS: Overall, 397 entered the run-in (mean 54.2 years, 235 males [59.2%]). At the end of SIIT, 374/396 participants (94.4%) had both FBG <7.0 mmol/L (<126 mg/dL) and 2-hour PBG <10 mmol/L (<180 mg/dL) and 282/396 (71.2%) had both FBG <6.1 mmol/L (<100 mg/dL) and 2-hour PBG <10 mmol/L. The mean first time taken to achieve FBG <7 mmol/L, 2-hour PBG <10 mmol/L, and both, was 4.35, 3.88, and 5.04 days, respectively. Hypoglycaemia occurred in 99 participants (24.9%). There was no severe hypoglycaemia. CONCLUSIONS: Titrating basal insulin first is an effective and safe method of SIIT in individuals with T2D, rapidly achieving target glucose levels with a relatively low rate of hypoglycaemia.

iGlarLixi (insulin glargine 100 U/ml plus lixisenatide) is effective and well tolerated in people with uncontrolled type 2 diabetes regardless of age: A REALI pooled analysis of prospective real-world data.

AIM: To evaluate the effectiveness and safety in routine clinical practice of insulin glargine/lixisenatide (iGlarLixi) in people with type 2 diabetes (T2D) according to age. METHODS: Patient-level data were pooled from 1316 adults with T2D inadequately controlled on oral antidiabetic drugs with or without basal insulin who initiated iGlarLixi for 24 weeks. Participants were classified into age subgroups of younger than 65 years (N = 806) and 65 years or older (N = 510). RESULTS: Compared with participants aged younger than 65 years, those aged 65 years or older had a numerically lower mean body mass index (31.6 vs. 32.6 kg/m2 ), a longer median diabetes duration (11.0 vs. 8.0 years), were more likely to receive prior basal insulin (48.4% vs. 43.5%) and had a lower mean HbA1c (8.93% [74.10 mmol/mol] vs. 9.22% [77.28 mmol/mol]). Similar and clinically relevant reductions in HbA1c and fasting plasma glucose from baseline to week 24 of iGlarLixi therapy were observed regardless of age. At 24 weeks, least-squares adjusted mean (95% confidence interval [CI]) change in HbA1c from baseline was -1.55% (-1.65% to -1.44%) in those aged 65 years or older and -1.42% (-1.50% to -1.33%) in those aged younger than 65 years (95% CI: -0.26% to 0.00%; P = .058 between subgroups). Low incidences of gastrointestinal adverse events and hypoglycaemic episodes were reported in both age subgroups. iGlarLixi decreased mean body weight from baseline to week 24 in both subgroups (-1.6 kg in those aged ≥ 65 years and -2.0 kg in those aged < 65 years). CONCLUSIONS: iGlarLixi is effective and well tolerated in both younger and older people with uncontrolled T2D.

Direct comparison two fixed-ratio combination glucagon-like peptide receptor agonist and basal insulin on glycemic and non glycemic parameters in type 2 diabetes.

BACKGROUND: Two types of fixed-ratio combinations of basal insulin and a glucagon-like peptide-1 receptor agonist (GLP-1RA) have been approved for use in type 2 diabetes. One is insulin degludec/liraglutide (iDergLira), and the other is insulin glargine/lixisenatide (iGlarLixi). Direct comparisons between these two combination is not available. METHODS: The retrospective study included 186 patients with type 2 diabetes mellitus (DM) with inadequate glycemic control on metformin and basal insulin (degludec, glargine 100, glargine 300) who were switched to fixed-ratio combination GLP-1 RA and basal insulin. Patients were divided into two groups based on the basal insulin before study: group I (n = 86) treated with degludec were switched to iDegLira and patients group II (n = 99), treated with glargine were switched to iGlarLixi. The aim of this study was to directly compare the effects between two fixed - ratio combination on glycemic parameters and non glycemic parameters. Follow up was 6 months. RESULTS: Mean HbA1c decreased similarly (- 1.2% vs.-1.1%). Higher percentage patients in iDegLira group had reached the HbA1c < 7% after 6 months (22% vs. 18.2%, p < 0.05). The mean change in fasting plasma glucose (FPG) was comparable for the two groups, while mean decrease postprandial plasma glucose (PPG) level were lower in iGlarLixi group (2 vs 1.8 mmol/l, p > 0.05). Change in body weight was significant in iDegLira group (1.8 kg vs. 0.7 kg, p < 0.001). At the end of the study patients showed decrease in total cholesterol (TC) and low-density lipoprotein (LDL) for 0.2 mmol/L in iDegLira, 0.1 mmol/l in iGlarLixi, triglycerides decreased 0.3 mmol/l in both groups, high-density lipoprotein(HDL) increased 0.1 mm/l in iGlarLixi. CONCLUSION: Our results showed that more patients with iDegLira had HbA1c less than 7% and these combination had better effect on weight loss. There was no difference observed in FPG and PPG, lipid profile and rate of hypoglycemia.

The efficacy of insulin degludec and insulin glargine over NPH insulin among toddlers and preschoolers with type 1 diabetes using glycemic variability and time in range.

Optimizing glycemic control without risking hypoglycemia is crucial in toddlers and preschoolers with type 1 diabetes (T1D) to avoid cognitive impairment later in life. Hence, this study aims to compare glycemic parameters among toddlers and preschoolers with T1D in relation to different basal insulins. Sixty toddlers and preschoolers with T1D with mean age of 3.53 ± 1.17 years (range, 2-6) and mean diabetes duration of 9.37 ± 1.85 months were randomly assigned into three equal groups; group A received insulin degludec, group B received insulin glargine, and group C were on NPH. At baseline, the three groups were matched regarding clinical and laboratory parameters (p > 0.05). They were followed up at 3 and 6 months for insulin daily dose (IDD), hypoglycemia and severe-hypoglycemia frequency, and glycated hemoglobin (HbA1c). At the study endpoint, continuous glucose monitoring (CGM) was assessed in a random sample of 10 patients from each group. The mean time in range (TIR) of the studied cohort was 55.07 ± 24.05%, and their mean coefficient of variation (CV) was 42.82 ± 11.69%. The TIR was significantly higher in the degludec group (69.36 ± 18.54) and the glargine group (55.43 ± 26.51) than the NPH group (32.56 ± 9.11), p < 0.001. Meanwhile, the CV was significantly lower in the degludec group (35.12 ± 6.47) than the gargine (44.1 ± 13.13) and the NPH (53.8 ± 7.54) groups, p < 0.001. The insulin degludec and glargine groups had significantly lower HbA1c (p = 0.002), hypoglycemia (p = 0.006), severe hypoglycemia (p = 0.029), and IDD (p = 0.015) than the NPH group. CONCLUSION: Insulin degludec and glargine resulted in better HbA1c and TIR with reduced hypoglycemia and IDD than NPH among toddlers and preschoolers with T1D. Moreover, CV was lowest in the insulin degludec group. WHAT IS KNOWN: • Insulin therapy is the mainstay of T1D management. • Optimal insulin therapy for young children with T1D should provide effective glycemic. WHAT IS NEW: • Insulin degludec and insulin glargine have better efficacy than NPH insulin among toddlers and preschoolers with T1D in the term of significantly lower coefficient of variation, HbA1c and IDD and significantly higher time in range. • Insulin degludec and insulin glargine have better safety in the term of less hypoglycemia and severe hypoglycemia episodes than NPH insulin among toddlers and preschoolers with T1D.

Validation of the classification for type 2 diabetes into five subgroups: a report from the ORIGIN trial.

AIMS/HYPOTHESIS: Data analyses from Swedish individuals with newly diagnosed diabetes have suggested that diabetes could be classified into five subtypes that differ with respect to the progression of dysglycaemia and the incidence of diabetes consequences. We assessed this classification in a multiethnic cohort of participants with established and newly diagnosed diabetes, randomly allocated to insulin glargine vs standard care. METHODS: In total, 7017 participants from the Outcome Reduction with Initial Glargine Intervention (ORIGIN) trial were assigned to the five predefined diabetes subtypes (namely, severe auto-immune diabetes, severe insulin-deficient diabetes, severe insulin-resistant diabetes, mild obesity-related diabetes, mild age-related diabetes) based on the age at diabetes diagnosis, BMI, HbA1c, fasting C-peptide levels and the presence of glutamate decarboxylase antibodies at baseline. Differences between diabetes subtypes in cardiovascular and renal outcomes were investigated using Cox regression models for a median follow-up of 6.2 years. We also compared the effect of glargine vs standard care on hyperglycaemia, defined by having a mean post-randomisation HbA1c ≥6.5%, between subtypes. RESULTS: The five diabetes subtypes were replicated in the ORIGIN trial and exhibited similar baseline characteristics in Europeans and Latin Americans, compared with the initially described clusters in the Swedish cohort. We confirmed differences in renal outcomes, with a higher incidence of events in the severe insulin-resistant diabetes subtype compared with the mild age-related diabetes subtype (i.e., chronic kidney disease stage 3A: HR 1.49 [95% CI 1.31, 1.71]; stage 3B: HR 2.25 [1.82, 2.78]; macroalbuminuria: HR 1.56 [1.22, 1.99]). No differences were observed in the incidence of retinopathy and cardiovascular diseases after adjusting for multiple hypothesis testing. Diabetes subtypes also differed in glycaemic response to glargine, with a particular benefit of receiving glargine (vs standard care) in the severe insulin-deficient diabetes subtype compared with the mild age-related diabetes subtype, with a decreased occurrence of hyperglycaemia by 13% (OR 1.36 [1.30, 1.41] on glargine; OR 1.49 [1.43, 1.57] on standard care; p for interaction subtype × intervention = 0.001). CONCLUSIONS/INTERPRETATION: Cluster analysis enabled the characterisation of five subtypes of diabetes in a multiethnic cohort. Both the incidence of renal outcomes and the response to insulin varied between diabetes subtypes. These findings reinforce the clinical utility of applying precision medicine to predict comorbidities and treatment responses in individuals with diabetes. TRIAL REGISTRATION: ORIGIN trial, ClinicalTrials.gov NCT00069784.

Comparative efficiency and safety of insulin degludec/aspart with insulin glargine in type 2 diabetes: a meta-analysis of randomized controlled trials.

Recent studies have found compared with insulin glargine (IGlar), insulin degludec/aspart (IDeg/Asp) may provide adequate glycemic control and prevent hypoglycemia events in type 2 diabetes mellitus (T2DM). Consequently, we performed a meta-analysis to appraise and compare the efficiency and safety of IDeg/Asp and IGlar in the treatment of T2DM. We sought the databases including PubMed, Embase, Scopus, Cochrane library to confirm related articles which inspected the effect of IDeg/Asp versus IGlar for the treatment of T2DM until May 2021. Finally, six randomized controlled trials (RCTs) of 1,346 patients were included. The results showed that IDeg/Asp significantly decreased the mean hemoglobin A1c (HbA1c) level but was prone to serious adverse events, and IGlar increased the nocturnal confirmed hypoglycemia events. Besides, there were no significant changes in other indicators, including mean fasting plasma glucose (FPG) level, nine-point self-measured plasma glucose (SMPG) level, and adverse events. What's more, we found that there was no significant difference in the occurrence of hypoglycemia overall, but our subgroup analysis of confirmed hypoglycemia revealed the population in this subgroup (duration of diabetes ≤11 years) might has its particularity effecting the hypoglycemia outcome. Concerning efficiency, IDeg/Asp may have advantages in controlling the mean HbA1c level. Regarding safety, IGlar might increase the risk of nocturnal confirmed hypoglycemia. Further evidence is needed to compare better the efficiency and safety of IDeg/Asp versus IGlar therapy.

Comparison of the effects of exenatide and insulin glargine on right and left ventricular myocardial deformation as shown by 2D-speckle-tracking echocardiograms.

Background: Exenatide is a glucagon-like peptide-1 (GLP-1) analogs. The effects of GLP-1 analogs on myocardial function are controversial. Aims: The purpose of this study is to compare the effects of exenatide and insulin glargine on subclinical right and left ventricular dysfunction. Methods and Material: In this study, 27 patients with type 2 diabetes were randomized into exenatide and insulin glargine treatment groups. The patients were monitored for six months by conventional echocardiography (ECHO) and 2D-speckle-tracking echocardiography (2D-STE) to evaluate right and left ventricular functions. Results: ECHO parameters did not change significantly pre- and post-treatment, except for the tricuspid annular plane systolic excursion (TAPSE) values. Post-treatment TAPSE values significantly increased in both groups compared to pre-treatment values. In the insulin group, values for 2D-STE parameters of the left ventricular global longitudinal strain (LVGLS) based on apical long-axis (ALA) images increased significantly (p: 0.047) compared to pre-treatment values; however, apical 4-chamber (A4C), apical 2-chamber (A2C), LVGLS, and right ventricular global longitudinal strain (RVGLS) values did not change. In the exenatide group, LVGLS based on A4C values improved (p: 0.048), while ALA, A2C, and LVGLS values did not change. Moreover, the RVGLS values improved significantly after exenatide treatment (p: 0.002). Based on 2D-STE parameters the two treatments did not differ statistically in either pre- or post-treatment periods. Conclusions: Glp-1 treatment can improve left ventricular regional and right ventricular global subclinical dysfunction. Therefore, early GLP-1 treatment may be recommended in diabetic patients with a high risk of cardiac dysfunction.

Efficacy and safety of LY2963016 insulin glargine versus insulin glargine (Lantus) in Chinese adults with type 2 diabetes: A phase III, randomized, open-label, controlled trial.

AIM: To compare the efficacy and safety of LY2963016 insulin glargine (LY IGlar) with insulin glargine (Lantus; IGlar) combined with oral antihyperglycaemic medications (OAMs) in insulin-naive Chinese patients with type 2 diabetes (T2D). MATERIALS AND METHODS: In this phase III, open-label trial, adult patients with T2D receiving two or more OAMs at stable doses for 12 weeks or longer, with HbA1c of 7.0% or more and 11.0% or less, were randomized (2:1) to receive once-daily LY IGlar or IGlar for 24 weeks. The primary outcome was non-inferiority of LY IGlar to IGlar at a 0.4% margin, and a gated secondary endpoint tested non-inferiority of IGlar to LY IGlar (-0.4% margin), assessed by least squares (LS) mean change in HbA1c from baseline to 24 weeks. RESULTS: Patients assigned to LY IGlar (n = 359) and IGlar (n = 177) achieved similar and significant reductions (p < .001) in HbA1c from baseline. LY IGlar was non-inferior to IGlar for change in HbA1c from baseline to week 24 (-1.27% vs. -1.23%; LS mean difference: -0.05% [95% CI, -0.19% to 0.10%]) and IGlar was non-inferior to LY IGlar. The study therefore showed equivalence of LY IGlar and IGlar for the primary endpoint. At week 24, there were no between-group differences in the proportion of patients achieving an HbA1c of less than 7.0%, seven-point self-measured blood glucose, insulin dose or weight gain. Adverse events, allergic reactions, hypoglycaemia and insulin antibodies were similar in the two groups. CONCLUSIONS: Once-daily LY IGlar and IGlar, combined with OAMs, provide effective and similar glycaemic control with comparable safety profiles in insulin-naive Chinese patients with T2D.

Similar immunogenicity profiles between the proposed biosimilar MYL-1501D and reference insulin glargine in patients with diabetes mellitus: the phase 3 INSTRIDE 1 and INSTRIDE 2 studies.

BACKGROUND: MYL-1501D is a proposed biosimilar to insulin glargine. The noninferiority of MYL-1501D was demonstrated in patients with type 1 diabetes and type 2 diabetes in 2 phase 3 trials. Immunogenicity of MYL-1501D and reference insulin glargine was examined in both studies. METHODS: INSTRIDE 1 and INSTRIDE 2 were multicenter, open-label, randomized, parallel-group studies. In INSTRIDE 1, patients with type 1 diabetes received MYL-1501D or insulin glargine over a 52-week period. In INSTRIDE 2, patients with type 2 diabetes treated with oral antidiabetic drugs, insulin naive or not, received MYL-1501D or reference insulin glargine over a 24-week period. Incidence rates and change from baseline in relative levels of antidrug antibodies (ADA) and anti-host cell protein (anti-HCP) antibodies in both treatment groups were determined by a radioimmunoprecipitation assay and a bridging immunoassay, respectively. Results were analyzed using a mixed-effects model (INSTRIDE 1) or a nonparametric Wilcoxon rank sum test (INSTRIDE 2). RESULTS: Total enrollment was 558 patients in INSTRIDE 1 and 560 patients in INSTRIDE 2. The incidence of total and cross-reactive ADA was comparable between treatment groups in INSTRIDE 1 and INSTRIDE 2 (P > 0.05 for both). A similar proportion of patients had anti-HCP antibodies in both treatment groups in INSTRIDE 1 at week 52 (MYL-1501D, 93.9 %; reference insulin glargine, 89.6 %; P = 0.213) and in INSTRIDE 2 at week 24 (MYL-1501D, 87.3 %; reference insulin glargine, 86.9 %; P > 0.999). CONCLUSIONS: In INSTRIDE 1 and INSTRIDE 2, similar immunogenicity profiles were observed for MYL-1501D and reference insulin glargine in patients with type 1 diabetes and type 2 diabetes, respectively. TRIAL REGISTRATION: ClinicalTrials.gov, INSTRIDE 1 ( NCT02227862 ; date of registration, August 28, 2014); INSTRIDE 2 ( NCT02227875 ; date of registration, August 28, 2014).

Quality of life in patients with type 2 diabetes after switching to insulin degludec: results from a cross-sectional survey.

PURPOSE: Five quality of life (QoL) domains are particularly important to patients with type 2 diabetes (T2D) using basal insulin-sense of physical well-being, sense of safety regarding hypoglycemia, sense of diabetes as burdensome, feelings of freedom and flexibility, and sleep quality. METHODS: An online survey assessed these QoL domains in adult patients with T2D in the USA who had switched from a previous basal insulin to insulin degludec (IDeg): modified versions of the World Health Organization (Five) Well-Being Index (WHO-5), Hypoglycemia Attitudes and Behavior Scale (HABS; confidence and anxiety subscales only), and Diabetes Distress Scale (DDS; emotional burden and regimen-related distress subscales only); three items assessing feelings of freedom and flexibility; and one item assessing sleep quality (hours of restful sleep). Patients rated each item for their previous basal insulin and currently while using IDeg. Correlations between sleep quality and the other QoL scales were also assessed. RESULTS: In total, 152 patients completed the survey and were included in the study sample. Patients reported significantly improved scores while using IDeg on all WHO-5, DDS, HABS, feelings of freedom and flexibility item scores, and total raw/mean subscale scores (P < 0.0001). Patients also reported a significantly greater number of hours of restful sleep [mean (SD) 6.6 (2.0) vs. 5.5 (1.8); P < 0.0001]. Better sleep quality statistically significantly correlated with improved QoL in all other domains assessed. CONCLUSIONS: Treatment with IDeg after switching from a previous basal insulin was associated with statistically significant improvements in all QoL domains assessed.