IGlar Group Research Articles

Abstract 16779: Tirzepatide Reduces High-Sensitivity C-reactive Protein in Patients With Type 2 Diabetes and High Cardiovascular Risk: A Post Hoc Analysis of the SURPASS-4 Trial

Background: People with type 2 diabetes (T2D) who have elevated levels of high-sensitivity C-reactive protein (hsCRP) face a greater risk of myocardial infarction and coronary death. Early data for tirzepatide (TZP), a GIP/GLP-1 receptor agonist, suggest a hsCRP lowering effect. Here, we compare the effect of TZP and insulin glargine (iGlar) on hsCRP in patients with T2D and established or high risk for cardiovascular (CV) disease. Methods: hsCRP concentration was quantified by immunoassay (Roche, Indianapolis, IN) with lower limits of detection at concentrations of 0.15 mg/L. Plasma was collected from 1995 fasted participants at baseline (329, 328, 338, and 1000 on 5, 10, 15 mg TZP and on iGlar, respectively) and 52 weeks in SURPASS-4. The % changes of hsCRP from baseline were estimated by mixed model with repeated measures. The shifts in hsCRP risk categories (hsCRP >3 mg/L or 1-3 mg/L versus <1 mg/L) from baseline to 52 weeks are reported. The linear relationship between % change from baseline of hsCRP and change in body mass index (BMI) was analyzed using Pearson correlation coefficient. Results: Baseline hsCRP (mean ± SD, 5.6 ± 12.5 mg/L) was elevated in this study population. Among the participants, 48%, 36%, and 16% were in the >3, 1-3 and <1 mg/L hsCRP categories, respectively. Participants in the elevated hsCRP categories had higher body weight and BMI at baseline. After 52 weeks of treatment, the 5, 10, 15 mg TZP and iGlar groups resulted in -38.0%, -44.2%, -47.8%, and 0.6% changes in the concentration of hsCRP, respectively. More TZP-treated patients improved their hsCRP categories when compared with iGlar-treated participants (Table). The reduction in hsCRP in the pooled TZP groups correlated with the reduction of BMI (r=0.07, p=0.049). Conclusions: Tirzepatide treatment significantly lowers hsCRP in patients with T2D and increased CV risk versus baseline and iGlar. Substantially more participants shift to a lower hsCRP category when compared with insulin glargine.

The efficacy and safety of beinaglutide alone or in combination with insulin glargine in Chinese patients with type 2 diabetes mellitus who are inadequately controlled with oral antihyperglycemic therapy: A multicenter, open-label, randomized trial.

To compare glycemic control in Chinese patients with type 2 diabetes mellitus (T2DM) whose blood glucose levels were inadequately controlled with oral antidiabetic drugs after beinaglutide alone or combined with insulin glargine (IGlar). In this 16-week multicenter, randomized clinical trial, 68 participants randomly received beinaglutide or IGlar for 8 weeks, then the two drugs in combination for 8 weeks. The primary outcomes were the proportion of individuals achieving their glycemic target and the change in glucose variability as measured with a continuous glucose monitoring system from baseline to 8 and 16 weeks. Both the beinaglutide and IGlar groups showed increased proportions achieving their glycemic target at 8 weeks, and the combination augmented the proportion reaching the glycated hemoglobin target from 25.42% at 8 weeks to 40.68% at 16 weeks. The beinaglutide group showed a significant reduction in body weight, body mass index, waist circumference, and systolic blood pressure. Beinaglutide elevated high-density lipoprotein cholesterol by 0.08 mmol/L (95% confidence interval [CI], 0.00-0.16), and diminished low-density lipoprotein cholesterol by 0.21 mmol/L (95% CI, 0.05-0.48), whereas IGlar showed no effect. Though IGlar was more efficient in lowering fasting plasma glucose than beinaglutide at comparable efficacies (to -1.57 mmol/L [95% CI, -2.60 to -0.54]), this difference was abolished in patients whose fasting C-peptide was ≥0.9 ng/mL. Beinaglutide exhibited a favorable hypoglycemic effect on patients with T2DM, and in combination with IGlar, glucose level was further decreased. Low fasting C-peptide in patients may reduce the glycemic response to beinaglutide therapy. We recommend that C-peptide levels be evaluated when using or switching to the novel glucagon-like peptide-1 receptor agonists beinaglutide. ClinicalTrials.gov: NCT03829891.

Efficacy and Safety of LY2963016 Insulin Glargine in Chinese Patients with Type1 Diabetes Previously Treated with Insulin Glargine (Lantus®): a Post Hoc Analysis of a Randomized, Open-Label, Phase3 Trial.

IntroductionLY2963016 insulin glargine (LY IGlar), a biosimilar of Lantus® insulin glargine (IGlar), demonstrated comparable efficacy and safety versus the reference product in Chinese patients with type 1 diabetes mellitus (T1DM) in the randomized, phase III ABES trial. This post hoc analysis aimed to provide the first evidence for switching from IGlar to LY IGlar in Chinese patients with T1DM.MethodsThis analysis included 210/272 patients with T1DM (77.2%) from the ABES trial who were receiving IGlar at screening. We compared antihyperglycemic efficacy, safety, and immunogenicity in patients randomized to LY IGlar (n = 104) versus those who continued to receive IGlar (n = 106).ResultsThere was no significant difference between groups in least-squares mean (LSMean) change in HbA1c from baseline to 24 weeks (LY IGlar − 0.10%, IGlar − 0.08%; LSMean difference [95% confidence interval] − 0.02% [− 0.24, 0.19]). At 24 weeks (last observation carried forward), a similar proportion of patients in each group achieved glycated hemoglobin less than 7.0% (LY IGlar 26.5%, IGlar 32.1%; P = 0.447) and 6.5% or less (LY IGlar 16.7%, IGlar 20.8%; P = 0.482). There were no significant differences between groups in LSMean of self-monitored blood glucose values, or total or basal insulin dose at 24 weeks. Patients in the LY IGlar and IGlar groups had a similar incidence of total hypoglycemia (blood glucose level 70 mg/dL or less, 91.4% vs. 92.5%) and treatment-emergent adverse events (AEs; 75.0% vs. 67.0%), and a low and similar incidence of serious AEs, injection site AEs, and allergic AEs. Similar proportions of patients in the LY IGlar and IGlar groups had treatment-emergent antibody responses (LY IGlar 27.2%, IGlar 28.3%) and detectable insulin antibodies (LY IGlar 52.4%, IGlar 53.8%).ConclusionIn Chinese patients with T1DM previously treated with IGlar, switching to LY IGlar for 24 weeks resulted in similar efficacy and safety outcomes as remaining on IGlar therapy.Clinical Trial RegistrationNCT03338023.Supplementary InformationThe online version contains supplementary material available at 10.1007/s13300-022-01262-8.

Comparing Time to Intensification between insulin Degludec/Insulin Aspart and Insulin Glargine

Background and Aims: The objective of the study was to compare the percent of patients with type 2 diabetes (T2D) requiring dose intensification and the time to dose intensification in patients on insulin degludec/insulin aspart (IDegAsp) versus those on basal insulin. Materials and Methods: Data were collected through retrospective chart review of patients with T2D being treated with insulin at a single center in India. The increase from once daily (OD) to twice daily dose or the addition of prandial insulin was considered as dose intensification. Chi-square test was conducted to compare the groups. Results: In the IDegAsp group (n = 515), 455 patients continued on the OD dose, and 60 patients (11.6%) were intensified. In the insulin glargine (IGlar) group (n = 173), 143 patients remained on the initial dose and 30 patients (17.34%) were intensified. Fewer patients on IDegAsp required treatment intensification than those on IGlar (P = 0.05). The time to treatment intensification (±standard deviation) was 11.98 ± 7.81 months in the IDegAsp group and 6.71 ± 6.86 months in the IGlar group. The time to treatment intensification was significantly longer in the IDegAsp than in the IGlar group (P = 0.0023). Conclusions: The study shows that significantly fewer patients on IDegAsp required dose intensification than those on IGlar. Additionally, the time to dose intensification was significantly delayed in patients on IDegAsp as compared to IGlar. However, HbA1c reduction with IGlar (nonintensified) was significant only at 6 months and failed to reach significance at 12 months, thereby pointing toward an early need for treatment intensification.

Metabolic and sympathovagal effects of bolus insulin glulisine versus basal insulin glargine therapy in people with type2 diabetes: A randomized controlled study.

Aims/IntroductionThis study compares the effects of two different insulin regimens – basal versus bolus insulin – on metabolic and cardiovascular autonomic function in Japanese participants with type 2 diabetes.Materials and MethodsParticipants were randomly assigned to groups for therapy with insulin glulisine (IGlu) or insulin glargine (IGla). The primary efficacy end‐point was glycemic variability, including M‐values, mean of glucose levels, and a blood glucose profile of seven time points before and after the intervention. The secondary end‐points included pleiotropic effects, including endothelial and cardiac autonomic nerve functions.ResultsBlood glucose levels at all time points significantly decreased in both groups. Post‐lunch, post‐dinner, and bedtime blood glucose levels were significantly lower in the IGlu group than in the IGla group. Nadir fasting blood glucose levels at the end‐point were significantly lower in the IGla group than in the IGlu group. The M‐value and mean blood glucose levels were significantly decreased from baseline in both groups, although the former was significantly lower in the IGlu group than in the IGla group. IGla, but not IGlu, was found to elevate 24‐h parasympathetic tone, especially during night‐time, and it decreased 24‐h sympathetic nerve activity, especially at dawn.ConclusionsBoth IGlu and IGla regimens reduced glucose variability, with IGlu bringing a greater reduction in M‐value. IGla, but not IGlu, increased parasympathetic tone during night‐time and decreased sympathetic nerve activity at dawn. These findings shed light on the previously unrecognized role of night‐time basal insulin supplementation on sympathovagal activity in type 2 diabetes patients.

Similar Cardiovascular Outcomes Between Insulin Detemir and Insulin Glargine In Type 2 Diabetic Patients With Extremely Atherosclerotic Cardiovascular Disease Risks

The cardiovascular outcomes of insulin detemir in patients with type 2 diabetes mellitus (T2DM) after acute coronary syndrome (ACS) or acute ischemic stroke (AIS) are unclear. The aim of our real-life cohort study was to evaluate the cardiovascular outcomes of insulin detemir (IDet) versus insulin glargine (IGlar) in T2DM patients after ACS or AIS. A retrospective cohort study was conducted between June 1, 2005, and December 31, 2013, utilizing the Taiwan National Health Insurance Research Database. A total of 3,129 ACS or AIS patients were eligible for the analysis. Clinical outcomes were evaluated by comparing 1,043 subjects receiving IDet with 2,086 propensity score-matched subjects who received IGlar. The primary composite outcome included cardiovascular (CV) death, nonfatal myocardial infarction (MI) and nonfatal stroke. The primary composite outcome occurred in 322 patients (30.9%) in the IDet group and 604 patients (29.0%) in the IGlar group (hazard ratio [HR], 1.12; 95% confidence interval [CI], 0.95 to 1.32) with a mean follow-up of 2.4 years. No significant differences were observed for CV death (HR, 1.09; 95% CI, 0.86 to 1.38), nonfatal MI (HR, 0.88; 95% CI, 0.66 to 1.19), and nonfatal stroke (HR, 1.15; 95% CI, 0.97 to 1.35). There were similar risks of all-cause mortality, hospitalization for heart failure and revascularization between the IDet group and the IGlar group (P = .647, .115, and .390 respectively). Compared with IGlar, in T2DM patients after ACS or AIS, IDet was not associated with increased risks of CV death, nonfatal MI, or nonfatal stroke. ACS = acute coronary syndrome; AIS = acute ischemic stroke; ASCVD = atherosclerotic cardiovascular disease; CI = confidence interval; CV = cardiovascular; DKA = diabetic ketoacidosis; HHF = hospitalization for heart failure; HHS = hyperosmolar hyperglycemic state; HR = hazard ratio; IDet = insulin detemir; IGlar = insulin glargine; MI = myocardial infarction; NHIRD = National Health Insurance Research Database; PCI = percutaneous coronary intervention; PSM = propensity score matching; T2DM = type 2 diabetes mellitus.

Meta-Analysis and Cost-Effectiveness Analysis of Insulin Glargine 100 U/mL Versus Insulin Degludec for the Treatment of Type 2 Diabetes in China.

To evaluate the efficacy and safety as well as the long-term cost-effectiveness of insulin glargine 100 U/mL (IGlar) versus insulin degludec (IDeg) for the treatment of type 2 diabetes mellitus (T2DM) from the Chinese healthcare system perspective. A systematic search of English and Chinese electronic databases for randomized controlled trials (RCTs) comparing IGlar with IDeg for the treatment of T2DM was performed, followed by a meta-analysis to compare the efficacy and safety of IGlar versus IDeg. The CORE Diabetes Model was used to estimate lifetime costs, quality-adjusted life years (QALYs) gained, and cost-effectiveness of IGlar versus IDeg. One-way and probabilistic sensitivity analyses were conducted to assess the underlying parameter uncertainty. Six RCTs were included in the meta-analysis. The IGlar group showed a statistically significant decrease in glycated hemoglobin (HbA1c) from baseline compared to the IDeg group (mean difference [MD] 0.08%, 95% confidence interval [CI] 0.01-0.14%, P = 0.02). Body mass index (BMI) control was numerically better in the IGlar group than in the IDeg group (MD 0.07kg/m2, 95% CI - 0.01 to 0.14kg/m2, P = 0.08). In terms of hypoglycemia, the incidence of non-severe overall hypoglycemia was comparable between the IDeg and IGlar patient groups (P > 0.05), while the incidence of non-severe nocturnal hypoglycemia (relative risk [RR 0.79], 95% CI 0.70-0.90, P < 0.01) and the event rates of non-severe overall (RR 0.91, 95% CI 0.85-0.97, P < 0.01) and non-severe nocturnal hypoglycemia (RR 0.91, 95% CI 0.85-0.97, P < 0.01) were lower in the IDeg group. The incidences and event rates of both severe overall and nocturnal hypoglycemia were similar for the two groups (P > 0.05). The cost-effectiveness analysis showed that IGlar is the dominant treatment option compared with IDeg, with a lifetime savings of 1004 Chinese yuan in direct medical costs and a net gain of 0.015 QALYs per patient. Both one-way and probabilistic sensitivity analyses confirmed the robustness of the results. IGlar is a cost-saving option with incremental effectiveness compared with IDeg for the treatment of T2DM in China. Sanofi China.

1032-P: Efficacy and Safety of the Insulin Glargine/Lixisenatide Fixed-Ratio Combination vs. Insulin Glargine in Japanese Patients with T2DM

The fixed ratio combination of insulin glargine/lixisenatide (iGlarLixi) has been shown in a Western population to improve glycemic control in a convenient single daily injection. This open-label trial assessed the efficacy and safety of 26-week treatment of iGlarLixi and insulin glargine (iGlar) in Japanese patients with T2DM inadequately controlled on basal insulin and oral antidiabetic drugs. After a 12-week run-in with metformin and iGlar, patients were randomized to iGlarLixi (n=255) or iGlar (n=257). Starting from a mean baseline (BL) HbA1c of 8.25%, the decrease in the iGlarLixi group was significantly greater than in the iGlar group (LS mean difference [SE]: -0.74% [0.063], p&amp;lt;0.0001) (Figure). Significantly more patients reached the HbA1c target of &amp;lt;7% at Week 26 with iGlarLixi than with iGlar (51.8% vs. 16.0%, p&amp;lt;0.0001). Change in body weight from BL to Week 26 was -0.51 kg with iGlarLixi and +0.55 kg with iGlar (p&amp;lt;0.0001). Both treatments were well tolerated. Documented symptomatic hypoglycemia (≤70 mg/dL) was similar in the two treatment groups (iGlarLixi: 18.8%, iGlar: 16.7%). Nausea was reported in 16.9% (iGlarLixi) and 0.8% (iGlar). In conclusion, iGlarLixi showed superior glycemic control to iGlar, with a beneficial effect on body weight, no additional risk of hypoglycemia, and lower rate of nausea than reported with lixisenatide. Disclosure H. Kaneto: Research Support; Self; Astellas Pharma Inc., AstraZeneca K.K., Chugai Pharmaceutical Co., Ltd., Daiichi Sankyo Company, Limited, Eli Lilly Japan K.K., Kissei Pharmaceutical Co., Ltd., Kowa Pharmaceutical Co. Ltd., Mitsubishi Tanabe Pharma Corporation, MSD K.K., Nippon Boehringer Ingelheim Co ., Ltd., Novartis Pharma K.K., Novo Nordisk Pharma Ltd., Ono Pharmaceutical Co., Ltd., Pfizer Japan Inc., Sanofi K.K., Sumitomo Dainippon Pharma Co., Ltd., Taisho Toyama Pharmaceutical Co., Ltd., Takeda Pharmaceutical Company Limited. Speaker's Bureau; Self; Astellas Pharma Inc., AstraZeneca K.K., Chugai Pharmaceutical Co., Ltd., Daiichi Sankyo Company, Limited, Eli Lilly Japan K.K., Kissei Pharmaceutical Co., Ltd., Kowa Pharmaceutical Co. Ltd., Mitsubishi Tanabe Pharma Corporation, MSD K.K., Nippon Boehringer Ingelheim Co ., Ltd., Novartis Pharma K.K., Novo Nordisk Pharma Ltd., Ono Pharmaceutical Co., Ltd., Pfizer Japan Inc., Sanofi K.K., Sumitomo Dainippon Pharma Co., Ltd., Taisho Toyama Pharmaceutical Co., Ltd., Takeda Pharmaceutical Company Limited. A. Takami: Employee; Self; Sanofi K.K. R. Spranger: Employee; Self; Sanofi-Aventis Deutschland GmbH. A. Amano: Employee; Self; Sanofi K.K. D. Watanabe: Employee; Self; Sanofi K.K. E. Niemoeller: Employee; Self; Sanofi. Stock/Shareholder; Self; Sanofi. Funding Sanofi K.K.

Efficacy and safety of oral basal insulin versus subcutaneous insulin glargine in type 2 diabetes: a randomised, double-blind, phase 2 trial

Oral insulin 338 (I338) is a long-acting, basal insulin analogue formulated in a tablet with the absorption-enhancer sodium caprate. We investigated the efficacy and safety of I338 versus subcutaneous insulin glargine (IGlar) in patients with type 2 diabetes. This was a phase 2, 8-week, randomised, double-blind, double-dummy, active-controlled, parallel trial completed at two research institutes in Germany. Insulin-naive adult patients with type 2 diabetes, inadequately controlled on metformin monotherapy or combined with other oral antidiabetic drugs (HbA1c 7·0-10·0%; BMI 25·0-40·0 kg/m2), were randomly assigned (1:1) to receive once-daily I338 plus subcutaneous placebo (I338 group) or once-daily IGlar plus oral placebo (IGlar group). Randomisation occurred by interactive web response system stratified by baseline treatment with oral antidiabetic drugs. Patients and investigators were masked to treatment assignment. Weekly insulin dose titration aimed to achieve a self-measured fasting plasma glucose (FPG) concentration of 4·4-7·0 mmol/L. The recommended daily starting doses were 2700 nmol I338 or 10 U IGlar, and maximum allowed doses throughout the trial were 16 200 nmol I338 or 60 U IGlar. The primary endpoint was treatment difference in FPG concentration at 8 weeks for all randomly assigned patients receiving at least one dose of trial product (ie, the full analysis set). The trial has been completed and is registered at ClinicalTrials.gov, number NCT02470039. Between June 1, 2015, and Oct 19, 2015, 82 patients were screened for eligibility and 50 patients were randomly assigned to the I338 group (n=25) or the IGlar group (n=25). Mean FPG concentration at baseline was 9·7 (SD 2·8) in the I338 group and 9·1 (1·7) in the IGlar group. Least square mean FPG concentration at 8 weeks was 7·1 mmol/L (95% CI 6·4-7·8) in the I338 group and 6·8 mmol/L (6·5-7·1) in the IGlar group, with no significant treatment difference (0·3 mmol/L [-0·5 to 1·1]; p=0·46). I338 and IGlar were well tolerated by patients. Adverse events were reported in 15 (60%) patients in the I338 group and 17 (68%) patients in the IGlar group. The most common adverse events were diarrhoea (three [12%] patients in each group) and nasopharyngitis (five [20%] in the I338 group and two [8%] in the IGlar group). Most adverse events were graded mild (47 of 68 events), and no severe adverse events were reported. One patient in the IGlar group had a treatment-emergent serious adverse event (urogenital haemorrhage of moderate intensity, assessed by the investigator as unlikely to be related to treatment; the patient recovered). Incidence of hypoglycaemia was low in both groups (n=7 events in the I338 group; n=11 in the IGlar group), with no severe episodes. I338 can safely improve glycaemic control in insulin-naive patients with type 2 diabetes with no evidence of a difference compared with insulin glargine, a widely used subcutaneously administered basal insulin. Further development of this particular oral insulin project was discontinued because I338 doses were high and, therefore, production of the required quantities of I338 for wide public use was deemed not commercially viable. Improvement of technologies involved in the product's development is the focus of ongoing research. Novo Nordisk.

Up-Titration Strategy After DPP-4 Inhibitor-Based Oral Therapy for Type 2 Diabetes: A Randomized Controlled Trial Shifting to a Single-Dose GLP-1 Enhancer Versus Adding a Variable Basal Insulin Algorithm.

IntroductionIt is unclear whether adding basal insulin or enhancing incretin signaling with a glucagon-like peptide-1 receptor agonist (GLP-1RA) is more effective as an up-titration strategy after dipeptidyl peptidase-4 inhibitor (DPP-4i)-based oral antidiabetic drug (OAD) therapy. GLP-1RAs can be injected without dose adjustment, unlike basal insulin. Our objective was to examine the efficacy of changing patients inadequately controlled with oral DPP-4i-based OAD therapy to injectable GLP-1RA and discontinuing the DPP4i versus adding basal insulin glargine (IGlar) with the continuation of the oral DPP4i.MethodsSixty patients with type 2 diabetes (T2DM) and glycated hemoglobin (HbA1c) between 7.0% and 10.0% on DPP-4i-based OAD therapy were randomized to either adding IGlar and remaining on the DPP-4i or liraglutide and discontinuing the DPP-4i for 24 weeks. Patients in the IGlar group started with 0.1 unit/kg and were titrated according to the algorithm. In the liraglutide group, the DPP-4i was replaced with liraglutide 0.9 mg/day, the maximum dose in Japan. We evaluated HbA1c, glycated albumin (GA), and anthropometrics.ResultsHbA1c was significantly lower at week 24 (− 1.0 ± 0.9% in the IGlar group and − 0.6 ± 0.8% in the liraglutide group), but the difference between groups was not significant. Changes in GA were similar (− 2.9 ± 3.2% vs. − 2.6 ± 3.2%) in both groups. Body weight (BW) was significantly lower only in the liraglutide group (+ 0.5 ± 2.6 kg vs. − 2.2 ± 2.0 kg). The rate of minor hypoglycemic episodes was similar for both groups.ConclusionFor poorly controlled T2DM on DPP-4i-based OAD therapy, switching to single-dose liraglutide to enhance incretin signaling is as effective as dose-titrated basal IGlar, but significant BW reduction was only seen in the liraglutide group. These results suggest that enhancing incretin signaling with a single-dose injectable GLP-1 RA might be an alternative to dose-titrated basal insulin therapy in patients with T2DM poorly controlled with DPP-4i-based OAD therapy. These findings should be confirmed in a longer and larger trial.Trial RegistrationTrial Registry (UMIN-CTR) as UMIN000012224.Electronic supplementary materialThe online version of this article (10.1007/s13300-018-0486-1) contains supplementary material, which is available to authorized users.

Efficacy and Safety of Insulin Degludec and Insulin Glargine U-100 in Hospitalized Patients with Type 2 Diabetes—An Open-Label, Randomized Controlled Study

Aims/Introduction: The short-term efficacy and safety of insulin degludec (IDeg) in patients with type 2 diabetes have not previously been reported. We evaluated target glycemic control and glucose variability in hospitalized patients with type 2 diabetes. Material and Methods: In an open-label, multicenter, randomized controlled trial, 74 patients were randomly assigned to an insulin glargine U100 (IGla) group (38 patients) or insulin degludec group (36 patients) and were administered Basal-bolus therapy during hospitalization. Continuous glucose monitoring was performed on Day 11 after the insulin treatment commenced, to verify that day’s glucose variability. Results: The proportion of patients achieving a fasting blood glucose level of 110 mg/dl and 2-hour postprandial blood glucose level of 180 mg/dl throughout at least a day during the observation period was 30.6% [95% confidence interval 18.2-45.5%, one-sided p-value = 0.057] (11/36) in the IGla group, and 31.3% [95% confidence interval 18.0-47.2%, one sided p-value = 0.056] (10/32) in the IDeg group. Although no significant difference was noted on the 6-point SMBG profiles in mean blood glucose levels between the groups, the IDeg group showed a significant improvement in the percentage change from baseline of mean blood glucose before lunch on Day 7 (p = 0.021) and after dinner on Day 12 (Day 7 before lunch: IGla group -29.5 ± 26.3%, IDeg group -44.5 ± 22.1%, p = 0.021; Day 12 after dinner: IGla group -34.2 ± 22.5%, IDeg group -51.1 ± 21.7%, p = 0.021). No significant differences were noted between the groups in the incidence of hypoglycemia or the glucose variability parameter data on continuous glucose monitoring. Conclusion: This study suggests that IDeg is comparable with IGla in short-term efficacy and safety for patients with type 2 diabetes in the initial phase of basal-bolus therapy. Disclosure J. Suzuki: None. T. Yamakawa: None. M. Shinoda: None. R. Sakamoto: None. K. Takahashi: None. Y. Terauchi: Research Support; Self; MSD K.K.. Speaker's Bureau; Self; MSD K.K.. Advisory Panel; Self; MSD K.K.. Research Support; Self; Ono Pharmaceutical Co., Ltd.. Speaker's Bureau; Self; Ono Pharmaceutical Co., Ltd.. Research Support; Self; Novartis Pharma K.K., Boehringer Ingelheim GmbH. Speaker's Bureau; Self; Boehringer Ingelheim GmbH. Advisory Panel; Self; Boehringer Ingelheim GmbH. Research Support; Self; Mitsubishi Tanabe Pharma Corporation. Speaker's Bureau; Self; Mitsubishi Tanabe Pharma Corporation. Advisory Panel; Self; Mitsubishi Tanabe Pharma Corporation. Research Support; Self; Daiichi Sankyo Company, Limited. Speaker's Bureau; Self; Daiichi Sankyo Company, Limited. Advisory Panel; Self; Daiichi Sankyo Company, Limited. Research Support; Self; Sanwa Kagaku Kenkyusho Co., Ltd.. Speaker's Bureau; Self; Sanwa Kagaku Kenkyusho Co., Ltd.. Research Support; Self; Novo Nordisk Inc.. Speaker's Bureau; Self; Novo Nordisk Inc.. Advisory Panel; Self; Novo Nordisk Inc.. Research Support; Self; Eli Lilly and Company. Speaker's Bureau; Self; Eli Lilly and Company. Advisory Panel; Self; Eli Lilly and Company. Research Support; Self; Sanofi. Speaker's Bureau; Self; Sanofi. Advisory Panel; Self; Sanofi. Research Support; Self; Sumitomo Dainippon Pharma Co., Ltd.. Speaker's Bureau; Self; Sumitomo Dainippon Pharma Co., Ltd.. Research Support; Self; Shionogi &amp; Co., Ltd.. Speaker's Bureau; Self; Shionogi &amp; Co., Ltd., Bayer Yakuhin, Ltd., Astellas Pharma US, Inc., AstraZeneca. Advisory Panel; Self; AstraZeneca, Teijin Pharma Limited.

New Medications for the Treatment of Diabetes.

New Medications for the Treatment of Diabetes.

Efficacy and Safety of Insulin Degludec versus Insulin Glargine: A Systematic Review and Meta-Analysis of Fifteen Clinical Trials.

Aims Insulin degludec (IDeg) and insulin glargine (IGlar) are both proved to be effective in diabetes. This study aimed to assess the effects and safety of IDeg versus IGlar. Methods A systematic literature search was conducted using the PubMed, EMBASE, and Cochrane Library electronic databases to identify all randomized controlled trials (RCTs). Results Fifteen RCTs were identified. The combined data showed that the decrease in the glycosylated hemoglobin (HbA1c) level was slightly different, and the proportion of patients who achieved HbA1c < 7% was similar between the IDeg and IGlar groups. Further, a statistically significant decrease in the fasting plasma glucose level was observed in the IDeg group as compared to the IGlar group. In patients with T2DM, IDeg was associated with lower rates of overall hypoglycemia. Nocturnal hypoglycemia was significantly lower in the case of IDeg than in the case of IGlar in both T1DM and T2DM patients. No statistically significant differences were observed between the groups. Conclusions Compared with IGlar, IDeg is associated with equivalent glycemic control and a statistically significantly lower rate of nocturnal hypoglycemia in patients with T1DM and T2DM. In T2DM patients, IDeg also provides better results in terms of overall hypoglycemia.

Effect of insulin degludec versus insulin glargine on glycemic control and daily fasting blood glucose variability in insulin-naïve Japanese patients with type 2 diabetes: I'D GOT trial.

Insulin degludec (IDeg) is an ultra-long-acting insulin that has a smooth time/action profile over more than 42h. The present study compared the effects of IDeg and insulin glargine (IGlar) on HbA1c reduction and on within-subject day-to-day variability of fasting blood glucose (FBG) in insulin-naïve patients with type 2 diabetes. Eligible patients were randomly allocated at a 3:1 ratio to receive once-daily IDeg (n=31) or IGlar (n=12). Both basal insulins were administered before breakfast and titrated to achieve a target FBG <110mg/dl. The primary endpoints were the change in HbA1c from baseline to 24weeks of treatment, as well as the standard deviation (SD) and coefficient of variation (CV) of FBG from 8 to 12weeks and from 20 to 24weeks. Secondary endpoints included the QOL evaluated by the Diabetes Therapy-Related QOL questionnaire. After 24weeks, HbA1c was decreased by 1.6% in the IDeg group and 1.7% in the IGlar at the same insulin dosage. At 24weeks, FBG was significantly lower in the IDeg group than in the IGlar group and the CV of FBG was significantly smaller in the IDeg group. The frequency of total and severe hypoglycemic episodes did not differ between the groups. In the IDeg group, QOL showed significant improvement regarding anxiety and dissatisfaction with treatment. Treatment with IDeg or IGlar achieved similar improvement in glycemic control in insulin-naïve patients with type 2 diabetes. The day-to-day variation of FBG was smaller in patients receiving IDeg.

Efficacy of switching from insulin glargine to insulin degludec in patients with type 1 diabetes: a 16-week retrospective study.

We retrospectively investigated the effect of switching from insulin glargine (IGlar) to insulin degludec (IDeg) on glycemic control in Japanese patients with type 1 diabetes mellitus. We also evaluated the dose of IDeg, and assessed weight gain and the risk of hypoglycemia after switching. Forty-five patients with type 1 diabetes were switched from IGlar (once daily or twice daily) to IDeg (once daily) during routine medical care. Data were collected for 16weeks after switching from IGlar to IDeg. The mean HbA1c (%) in weeks 4, 8, 12, and 16 was lower than it was in week 0 (8.0±1.0, 8.0±1.4, 7.9±1.1, 7.6±1.0 vs. 8.3±1.3%, p<0.01). The total basal insulin dose (TBD) was significantly lower after 16weeks of IDeg as compared to IGlar treatment (0.30±0.12 vs. 0.24±0.11U/kg/day, p=0.001). In the twice-daily IGlar group, TBD showed a significant decrease from 0.33±0.12 to 0.26±0.11U/kg/day (p<0.001) after switching to IDeg. In the once-daily IGlar group, TBD showed a slight but not significant decrease from 0.23±0.08 to 0.20±0.09U/kg/day (p=0.97). Hypoglycemic episodes were transiently increased, but the change was not significant. The blood glucose fluctuation was evaluated from self-monitoring data and the coefficient of variation (CV) was calculated. The CV showed only a minimal change from 48.3±17.1 to 48.6±14.2% at 12weeks after switching to IDeg (p=0.73). In conclusion, once-daily IDeg improved glycemic control in patients with type 1 diabetes compared to the control achieved with IGlar, without increasing the risk of hypoglycemia. When switching from IGlar (especially twice daily), it is recommended that the initial dose of IDeg should be reduced in order to decrease the risk of hypoglycemia.

The efficacy and safety of human glucagon-like peptide-1 analogue liraglutide in newly diagnosed type 2 diabetes with glycosylated hemoglobin A1c > 9

To evaluate the efficacy and safety of human glucagon-like peptide-1 analogue liraglutide in newly diagnosed type 2 diabetes mellitus (T2DM) with glycosylated hemoglobin A1c (HbA1c) > 9%. This was an open-labelled, randomized, parallel-group, treat-to-target trial. Newly diagnosed T2DM patients with HbA1c > 9% were enrolled. These patients were treated with metformin with repaglinide and randomized to receive once-daily liraglutide (LIRA, n=25) or the insulin glargine (IGla, n=24) at bedtime. Efficacy and safety were assessed and compared after 18-month treatment. (1) Compared with the baseline, patients with LIRA had significantly reduced mean body weight,BMI and waist circumference (P < 0.01), whereas, the above indexes were increased (P < 0.01) in patients treated with IGla. (2) After 18 months of treatment, fasting plasma glucose (FPG), 2-hour plasma glucose after a 75g oral glucose load (2hPG) and HbA1c were significantly improved in all patients (P < 0.01), with 2hPG, mean blood glucose (MBG), the largest amplitude of glycemic excursions (LAGE), mean amplitude of glycemic excursions (MAGE) were significantly lower in LIRA group than in IGla group (all P < 0.05). (3) HOMA-IR decreased in both groups (P < 0.05). However, ΔI30/ΔG30, AUCCP180 and Matsuda index were only significantly increased in patients treated with LIRA (respectively, 4.88 ± 1.55 vs 7.60±1.91, 9.23 ± 2.66 vs 13.18 ± 2.72, 39.28 ± 20.35 vs 54.64 ± 23.34, all P < 0.01), while HOMA-IR reduced (4.41 ± 1.58 vs 3.52 ± 1.44, P < 0.05). But in IGla group only HOMA-IR was reduced (4.92 ± 1.84 vs 4.57 ± 1.80, P < 0.05). The index of ΔI30/ΔG30, AUCCP180 and Matsuda index in LIRA group are higher than those of indexes in IGla group(respectively, 7.60 ± 1.91 vs 4.18 ± 1.00, 13.18 ± 2.72 vs 10.53 ± 2.68,54.64 ± 23.34 vs 41.65 ± 17.84, all P < 0.05), while HOMA-IR is lower (3.52 ± 1.44 vs 4.57 ± 1.80, P< 0.05). (4) The rate of HbA1c ≤ 6.5% and the dosages of oral anti-diabetic drugs in LIRA group were significantly better than that in IGla group. (5) No significant differences were observed in hypoglycemic episodes and adverse events between two groups. It seems that liraglutide is superior to insulin glargine in newly diagnosed T2DM patients with HbA1c > 9% in improving beta-cell function, insulin sensitivity and glucose homeostasis.

Lower risk of hypoglycaemia and greater odds for weight loss with initiation of insulin detemir compared with insulin glargine in Turkish patients with type 2 diabetes mellitus: local results of a multinational observational study.

BackgroundThe purpose of this analysis is to evaluate the safety and effectiveness of insulin initiation with once-daily insulin detemir (IDet) or insulin glargine (IGlar) in real-life clinical practice in Turkish patients with type 2 diabetes mellitus (T2DM).MethodsThis was a 24-week multinational observational study of insulin initiation in patients with T2DM.ResultsThe Turkish cohort (n = 2886) included 2395 patients treated with IDet and 491 with IGlar. The change in glycosylated haemoglobin (HbA1c) from the pre-insulin levels was -2.21% [95% confidence interval (CI) -2.32, -2.09] in the IDet group and -1.88% [95% CI -2.17, -1.59] in the IGlar group at the final visit. The incidence rate of minor hypoglycaemia increased in both groups from the pre-insulin to the final visit (+0.66 and +2.23 events per patient year in the IDet and IGlar groups, respectively). Weight change in the IDet group was -0.23 kg [95% CI -0.49, 0.02 kg], and +1.55 kg [95% CI 1.11, 2.00 kg] in the IGlar group. Regression analysis with adjustment for previously identified confounders (age, gender, duration of diabetes, body mass index, previous history of hypoglycaemia, microvascular disease, number and change in oral anti-diabetic drug therapy, HbA1c at baseline and insulin dose) identified an independent effect of insulin type (IDet versus IGlar) with a risk of at least one episode of hypoglycaemia (odds ratio (OR): 0.33 [95% CI 0.21, 0.52], p <0.0001), and weight loss ≥1 kg (OR: 1.75 [95% CI 1.18, 2.59], p = 0.005), but not on HbA1c (+0.05% [95% CI -0.15, 0.25%], p = 0.6).ConclusionsInitiation of basal insulin analogues, IDet and IGlar, were associated with clinically significant glycaemic improvements. A lower risk of minor hypoglycaemia and greater odds of weight loss ≥1 kg was observed with IDet compared with IGlar.Trial registrationNCT00825643 and NCT00740519

A comparison of biphasic insulin aspart and insulin glargine administered with oral antidiabetic drugs in type 2 diabetes mellitus - a systematic review and meta-analysis

It is uncertain whether the addition of biphasic insulin analogues to oral antidiabetic drugs (OADs) is as effective and safe as basal insulin in patients with type 2 diabetes mellitus (T2DM). We performed a systematic review to compare glycaemic control and selected clinical outcomes in T2DM patients inadequately controlled with OADs whose treatment was intensified by adding biphasic insulin aspart (BIAsp 30) or insulin glargine (IGlar). The analysis included randomised controlled trials (RCTs) identified by a systematic literature search in medical databases (MEDLINE, EMBASE, The Cochrane Library and other sources) up to March 2013. Studies met the inclusion criteria if they compared BIAsp 30 vs. IGlar added to at least one OAD in T2DM patients. Trials applying different OADs in both treatment arms were also included. Results were presented as weighted mean difference (WMD) or odds ratio (OR) with a 95% confidence interval (CI). Five trials, including a total number of 1758 patients followed up from 24 to 28weeks, were identified. Quantitative synthesis demonstrated that BIAsp 30 reduced HbA1c level more efficiently than IGlar [5 RCTs; WMD (95% CI): -0.21% (-0.35%, -0.08%)]. Differences were observed in favour of BIAsp for lower mean prandial glucose increment [3RCTs; WMD (95% CI): -14.70mg/dl (-20.09, -9.31)]; no difference was observed for fasting plasma glucose [3 RCTs; WMD (95% CI): 7.09mg/dl (-15.76, 29.94)]. We found no evidence for higher risk of overall [2 RCTs; 63% vs. 51%; OR=1.77 (0.91; 3.44)] and severe hypoglycaemic episodes [4 RCTs; 0.98% vs. 1.12%; OR (95% CI)=0.88 (0.31, 2.53)] in the BIAsp 30 group as compared with IGlar group. Twice-daily administration of BIAsp 30 resulted in larger weight gain [2 RCTs; WMD (95% CI)=1.78kg (1.04; 2.52)]. BIAsp 30 added to OAD therapy results in a better glycaemic control as compared with IGlar in T2DM patients. BIAsp 30 use is associated with slightly larger weight gain but no rise in risk of severe hypoglycaemic episodes.

Treat-to-target comparison between once daily biphasic insulin aspart 30 and insulin glargine in Chinese and Japanese insulin-naïve subjects with type 2 diabetes

Objective:To investigate whether once daily biphasic insulin aspart 30 (BIAsp 30) is noninferior to once daily insulin glargine (IGlar) among Chinese and Japanese insulin-naïve subjects with type 2 diabetes mellitus (T2DM).Research design and methods:This was a 24 week treat-to-target trial (NCT01123980) that included patients with T2DM who were poorly controlled on a combination of metformin and insulin secretagogue (or with a maximum of one more OAD) for 6 months. Patients were randomized to once daily BIAsp 30 or once daily IGlar and their secretagogue standardized to glimepiride 4 mg/day, metformin to 1500 or 2500 mg/day before randomization.Results:At Week 24, mean change from baseline in HbA1c was −0.78 ± 0.88% (mean ± SD) and −0.65 ± 0.92% (−8.49 ± 9.65 and −7.08 ± 10.1 mmol/mol) for the BIAsp 30 (n = 261) and IGlar (n = 260) groups, respectively. The estimated between-group difference (BIAsp 30 vs IGlar) in HbA1c change was −0.12% (95% CI: −0.25, 0.02) (−1.28 mmol/mol [95% CI: −2.75, 0.19]), thus treatment with BIAsp 30 was noninferior to IGlar with respect to HbA1c (non-inferiority margin 0.4%). Although reduction in mean 9-point self-measured plasma glucose (SMPG) profile was comparable between the two groups, BIAsp 30 showed significantly lower PG levels at three time points post-dinner and a higher PG level before dinner compared to the IGlar group (all p < 0.05). Comparable number of subjects reported hypoglycemic events (155 [59.4%] for BIAsp 30, 148 [56.9%] for IGlar).Conclusions:BIAsp 30 once daily showed similar HbA1c reduction and a similar safety profile to IGlar when used in insulin-naïve Chinese and Japanese patients on metformin and a sulfonylurea. Moreover, it provided a better coverage of post-dinner glycemic control needs than those who received IGlar. The open-label design and insufficient insulin dose titration were the main limitations of the study.Trial registration: ClinicalTrials.gov identifier: NCT01123980.

Insulin degludec compared with insulin glargine in insulin-naïve patients with type 2 diabetes: A 26-week, randomized, controlled, Pan-Asian, treat-to-target trial.

Insulin degludec (IDeg) is an ultra-long-acting basal insulin with a consistent action profile of >42h. This trial compared the efficacy and safety of IDeg with insulin glargine (IGlar) in insulin-naïve Asian patients with type 2 diabetes. In this multinational, 26-week, open-label, treat-to-target trial, 435 participants (202 females, 233 males; mean age 58.6years; mean body mass index 25kg/m(2); mean glycated hemoglobin [HbA1c] 8.5%) were randomized (2:1) to IDeg or IGlar, each administered once daily with ≥1 oral antidiabetic drug(s) (OAD). After 26weeks, HbA1c had decreased by 1.24 and 1.35% in the IDeg and IGlar groups, respectively (treatment difference [IDeg - IGlar] 0.11%, 95% confidence interval [CI] -0.03 to 0.24), confirming non-inferiority. Rates of overall confirmed hypoglycemia were similar for IDeg and IGlar during the full trial period (3.0 vs 3.7 episodes/patient-year of exposure [PYE]; rate ratio [RR] 0.82, 95% CI 0.60 to 1.11, P=0.20), but significantly lower (by 37%) for IDeg during the maintenance period (from week 16 onward; RR 0.63, 95% CI 0.42 to 0.94, P=0.02). No significant difference in the rate of nocturnal confirmed hypoglycemia was found between IDeg and IGlar in the full trial period (0.8 vs 1.2 episodes/PYE; RR 0.62, 95% CI 0.38 to 1.04, P=0.07) or maintenance period (RR 0.52, 95% CI 0.27 to 1.00, P=0.05). Adverse event rates were similar between treatments. Initiating insulin therapy with IDeg in Asian patients with type 2 diabetes, inadequately controlled with OADs, provides similar improvements in long-term glycemic control to IGlar, but at a significantly lower rate of overall confirmed hypoglycemia once stable glycemic control and insulin dosing are achieved. This trial was registered with www.clinicaltrials.gov (no. NCT01059799).