Premixed Insulin Analogues Research Articles

The status of blood glucose monitoring and its influencing factors in Chinese patients with type 2 diabetes initiating premixed insulin: A prospective real-world study

ObjectiveThis study aimed to assess the current state of self-monitoring of blood glucose (SMBG) in Chinese patients initiating premixed insulin and its influential factors. Research Design and MethodsThis is a single-arm, multi-center, prospective real-world study enrolling a total of 8214 adult patients with type 2 diabetes mellitus (T2DM) newly initiated premixed insulin analogues. Each patient was followed up for 12 weeks, and the data related to SMBG was collected at week 1, week 4, week 8 and week 12, while data related to glycated hemoglobin were collected at week 1 and week 12. The primary outcome was the frequency of SMBG over 12 weeks. ResultsAt week 12, 83.3 % monitored blood glucose at least once, while 20.3 % of participants continued SMBG every week. The average monitoring frequency was 4.78 times/week over the first 4 weeks and 3.33 times/week over 12 weeks. The patients with a higher frequency of SMBG had better control of blood glucose. ConclusionsThis study found that most T2DM patients would take SMBG but the adherence decreased over time. The adherence to SMBG in Chinese T2DM patients was influenced by age, insulin dosage, education level, and diabetes duration. SMBG benefited the improvement of glycemic control.

Comparison of Insulin Analogs and Human Insulins: A Narrative Review

Abstract Introduction Since insulin analogs have pharmacological properties that are similar to the normal physiological action of insulin, it has been suggested that they provide better glucose control and less rates of hypoglycemia compared to human insulins. Methods We performed a narrative, nonsystematic review of the literature including clinical trials, systematic reviews, meta-analyses, and professional guidelines related to the comparison of human insulins and insulin analogs in terms of glucose control, safety profile, and cost. Results Long-acting basal insulins result in mild improvement in glucose control and less rates of nocturnal hypoglycemic compared to neutral protamine Hagedorn insulin, mainly among patients with type 1 diabetes. Rapid-acting insulin analogs provide better glucose control and lower rates of hypoglycemia compared to regular insulin among patients with type 1 diabetes, whereas no advantage has been shown for insulin analogs among patients with type 2 diabetes for glucose control or hypoglycemia. Premixed insulin analogs provided no advantage in glucose control and inconsistent benefit in lowering the rates of hypoglycemia compared to human premixed insulins among patients with type 2 diabetes. The cost of insulin analogs is significantly higher than human insulins, and favorable cost-effectiveness has only been demonstrated for rapid-acting insulin analogs in type 1 diabetes. Conclusion Currently available evidence supports the use of rapid-acting insulin analogs and possibly long-acting basal insulin over human insulins for patients with type 1 diabetes. For patients with type 2 diabetes, the use of long-acting insulin analogs may be recommended for selected patients who are at an increased risk of significant hypoglycemia, while no clear benefits of meal insulin analogs over human insulins have been observed.

Abstract #1400954: Profile of Type 2 Diabetes Patients Treated with Insulin and Their Knowledge on Practical Aspects of Usage of Insulin

Initiation and continuation of insulin in Type 2 Diabetes patients has been one of the major challenges faced by physicians of the developing world due to various factors like cost, availability, literacy status, and patient's belief that its use is the only last option. The aim of this study was to know the clinico-epidemiological characteristics of Type 2 Diabetes patients treated with insulin and their knowledge of practical aspects of insulin use. This descriptive comparative cross-sectional study was conducted in Koshi Hospital, Biratnagar, Nepal from 1st January 2022 to 31st May 2022 applying consecutive sampling and face-to-face interviews after informed verbal consent. Out of 485 participants, 59.6 percent were male (the rest 40.4 percent female) with a mean age of participants 52.04 ± 11.31 years, and 12 percent of them using insulin (premixed human insulin, premixed insulin analogs, basal insulin analogs, and basal-bolus insulin by 43.01, 12.06, 36.2 and 8.62 percent respectively). Of those using insulin, 41.37 percent were ≥ 60 years old with 62.06 percent male participants, 44.83 percent with diabetes for ≥ 10 years, 50 percent with a degree of school level education or more, and 68.97 percent were aware of chronic complications of diabetes. Participants treated with insulin were older with a longer duration of disease, more literate, more frequent monitoring their blood sugar level, more aware of hypoglycemia management at home, and more aware of chronic complications of diabetes than their counterparts. Among insulin-taking participants, appropriate knowledge of insulin storage, proper site, correct technique of administration, hypoglycemia management at home, and mixing insulin prior to use among those using premixed insulin was found in 94.83, 62.06, 56.89, 22.8, and 50 percent respectively. This study explores the need for proper counseling for Type 2 Diabetes patients by physicians and counselors focusing on the advantages of timely initiation of insulin and knowledge on practical aspects of insulin use, especially in the developing world.

Effectiveness of the Lilly Connected Care Program in Improving Glycemic Management Among Patients With Type 2 Diabetes in China: Retrospective Real-world Study.

Type 2 diabetes mellitus (T2DM) is a worldwide public health concern. Mobile health management platforms could be a potential way to achieve effective glycemic control. This study aimed to evaluate the real-world effectiveness of the Lilly Connected Care Program (LCCP) platform in glycemic control among patients with T2DM in China. This retrospective study included Chinese patients with T2DM (aged ≥18 years) from April 1, 2017, to January 31, 2020, for the LCCP group and from January 1, 2015, to January 31, 2020, for the non-LCCP group. Propensity score matching was used to match the LCCP and non-LCCP groups to reduce confounding, with covariates including age, sex, the duration of diabetes, baseline hemoglobin A1c (HbA1c), and the number of oral antidiabetic medication classes. HbA1c reduction over 4 months, the proportions of patients achieving an HbA1c reduction of ≥0.5% or ≥1%, and the proportions of patients reaching to target HbA1c level of ≤6.5% or <7% were compared between the LCCP and non-LCCP groups. Multivariate linear regression was used to assess factors associated with HbA1c reduction. A total of 923 patients were included, among whom 303 pairs of patients were well matched after propensity score matching. HbA1c reduction during the 4-month follow-up was significantly larger in the LCCP group than the non-LCCP group (mean 2.21%, SD 2.37% vs mean 1.65%, SD 2.29%; P=.003). The LCCP group had a higher proportion of patients with an HbA1c reduction of ≥1% (209/303, 69% vs 174/303, 57.4%; P=.003) and ≥0.5% (229/303, 75.6% vs 206/303, 68%; P=.04). The proportions of patients reaching the target HbA1c level of ≤6.5% were significantly different between the LCCP and non-LCCP groups (88/303, 29% vs 61/303, 20.1%; P=.01), whereas the difference in the proportions of patients reaching the target HbA1c level of <7% was not statistically significant (LCCP vs non-LCCP: 128/303, 42.2% vs 109/303, 36%; P=.11). LCCP participation and higher baseline HbA1c were associated with a larger HbA1c reduction, whereas older age, longer diabetes duration, and higher baseline dose of premixed insulin analogue were associated with a smaller HbA1c reduction. The LCCP mobile platform was effective in glycemic control among patients with T2DM in China in the real world.

Insulin analogs in the treatment of type II diabetes and future perspectives

The discovery of insulin by Banting and Best marked 100 years in 2021, and it was a life-saving treatment modality for type II diabetes mellitus (T2DM). Insulin is a natural hormone that has been used extensively in T2DM patients since its discovery. Currently, insulin analogs are also available in different formulations for T2DM management, overcoming the limitations of human insulin with better safety and side effect profiles. The insulin analogs like the rapid-acting analogs (Aspart, lispro, glulisine), the long-acting basal analogs (Glargine, detemir), the ultra-long acting (Insulin degludec), and the premixed insulin analog formulations (75% Neutral protamine lispro, 25% lispro; 50% neutral protamine lispro, 50% lispro; 70% protamine aspart, 30% aspart) have been prepared through genetic engineering while preserving the basic insulin profile. A large number of studies have demonstrated their clinical effects on glycated hemoglobin test (HbA1c) in achieving glycemic control and thereby lowering the microvascular and macrovascular complications of T2DM with less traditional side effects of regular human insulin, mainly the risk of hypoglycemia, postprandial glycemic excursions, and weight gain. This review explores the currently available insulin analogs, their clinical implications, pharmacokinetics (PK), pharmacodynamics (PD), safety profile, and cost-effectiveness. We also discuss the future developments in the management of T2DM, especially the scientific advancements surrounding the novel insulin formulations, including the biosimilar insulin, and the innovative insulin delivery methods, such as oral and inhaled insulin.

Progranulin and chemerin plasma level in obese patients with type 2 diabetes treated with a long-acting insulin analogue and premixed insulin analogue.

Diabetes, referred to as the first non-infectious epidemic, covers a heterogenous group of metabolic diseases marked by hyperglycemia resulting from a defect of insulin secretion and/or insulin resistance. Highly endocrine active adipocytes, particularly those located in white adipose tissue, constitute a source of cytokines, growth factors and complement component as well as adipocytokines including chemerin and progranulin could be the key molecules in the pathomechanism of hypertension, dyslipidemia, metabolic disorders or diabetes type 2. In this study, it was decided to verify the existence of possible relationships between the plasma concentration of progranulin and chemerin and the values of intermediate indices of insulin sensitivity and insulin resistance in patients, both before and after the 6-month insulin therapy by long-acting insulin analogue and premixed insulin analogue. The level of laboratory parameters in blood plasma collected from the control group and from obese individuals with type 2 diabetes mellitus was estimated with the test kits using enzyme-linked immunosorbent assay (ELISA): the test of Mediagnost E103 GmbH GmbH, Reutlingen, Germany for progranulin; the test of BioVendor R&D, Brno, Czech Republic for chemerin. The aim of this study was to assess the progranulin and chemerin plasma level in obese individuals with type 2 diabetes, before and after 6 months of pharmacological treatment with a long-acting analogue human insulin or premixed insulin. In the blood plasma of untreated diabetics - in contrary to progranulin plasma concentration in diabetic patients after management implementation - progranulin was found to occur in a significantly higher concentration in relation to the level of this protein in the blood plasma of control group individuals. Despite the fact that 6-month therapy, both with the insulin mixture and with the long-acting analogue in people with diabetes, does not significantly affect the plasma chemerin concentration, the high, negative correlation between the progranulin and chemerin levels in the blood of individuals of the control group, and a positive one between the levels of progranulin and chemerin in people with diabetes before and after treatment was found. The conducted studies indicated the modified, in the course of diabetes type 2, mutual quantitative relations between progranulin and chemerin - the biological mediators of systemic metabolism, reflecting their active participation in the pathogenetic changes underlying type 2 diabetes. The obtained study results indicate a modification of mutual relationships of the adipocytokines assessed in the paper - progranulin and chemerin, associated with the development of the systemic inflammatory response occurring in the course of obesity which, by inducing insulin resistance, may consequently lead to type 2 diabetes. Taking into consideration the fact that the plasma progranulin and chemerin concentrations in obese patients with type 2 diabetes subjected to pharmacotherapy have not been assessed so far, it is possible that the obtained study results may cast light on the potential influence of the applied treatment on the systemic changes of the both adipocytokines involved in the pathomechanism of the mentioned disorder and thus create the possibility of implementing new therapeutic strategies in the management of patients with diabetes, which is an increasingly common, fast-spreading metabolic disease considered as a non-infectious epidemic of the 21st century.

Real-World Effectiveness and Safety of Insulin Glargine 300 U/mL in Patients with T2D Uncontrolled on NPH or Premixed Insulins as Part of Routine Clinical Practice in Bulgaria: ToUPGRADE Study

IntroductionThe aim of this study is to demonstrate the real-life effectiveness and safety of insulin glargine 300 U/mL (Gla-300) in patients with type 2 diabetes (T2D) previously uncontrolled on NPH ± prandial insulin or premixed insulins in routine clinical practice in Bulgaria.MethodsThis was a 24-week prospective, observational study performed in 40 inpatient and outpatient sites across the country.ResultsA total of 286 patients were included in the study. The mean age (± SD) was 61.2 ± 10.0 years with duration of diabetes of 11.64 ± 7.5 years and body mass index (BMI) of 32.1 ± 5.7 kg/m2. HbA1c before Gla-300 initiation was 9.8 ± 1.0%, and fasting plasma glucose (FPG) was 13.1 ± 3.4 mmol/L. HbA1c and FPG change from baseline to week 24 was − 1.86% (p < 0.001) and − 4.8 mmol/L (p < 0.001), respectively. The proportion of patients reaching their individualized HbA1c at week 24 was 39.1% (95% CI 33.3–45.1%), while the proportion of patients reaching their individualized HbA1c target without confirmed and/or severe hypoglycaemia was 34.8% (95% CI 29.2–40.7%). At study end, 19.0% (95% CI 14.6–24.1%) achieved HbA1c < 7%. Body weight decreased from 88.3 to 87.0 kg from baseline to week 24 with mean change of − 1.3 kg (p < 0.001). The incidence and event rates of anytime confirmed (≤ 3.9 mmol/L) and/or severe hypoglycaemia were low: 7.7% and 0.42 events per patient-year, respectively. The overall Insulin Treatment Satisfaction Questionnaire (ITSQ) score increased from 53.2 to 78.2 from baseline to week 24 and the difference of 25.1 ± 21.5 points was significant (p < 0.001).ConclusionsIn real-life settings, Gla-300 significantly improved glycaemic control and insulin treatment satisfaction in people with T2D who were inadequately controlled with NPH ± prandial insulin or premixed insulin analogues. Improvement of glycaemic control was associated with a very low risk of hypoglycaemia and with significant weight loss irrespective of the previous insulin regimen. Video Supplementary InformationThe online version contains supplementary material available at 10.1007/s13300-021-01022-0.

Saudi Consensus for Low-Premixed Insulin Analogues in Type 2 Diabetes: Consensus Report

Dear Dr. Martin Hovland, We learned from the literature that premixed insulins are short-acting insulin or rapid-acting insulin analogue mixed with intermediate-acting insulin in a fixed ratio, addressing FBG and PPBG in one injection. There are two categories; high-mix and low-mix premixed insulins. We, a Saudi task force, gathered to develop an explicit, evidence-based consensus for the use of the low-mix premixed insulin for better glycemic control. The treatment with premixed aspart 30 was non-inferior to treatment with premixed insulin lispro 25. In addition, Self-monitored blood glucose levels were comparable. Safety profiles were similar between both treatments, as was the incidence of hypoglycemic episodes. The switch between both products of the low-mix family can be carried out without any problem. Both products of the low-mix premixed insulin analogues aspart 30/70 and premixed insulin lispro 25/75 have comparable efficacy and safety as shown from the medical literature. Therefore, we can change from one to another safely as demonstrated by the US FDA statement. In addition, the ergonomic features of KwikPen’s design and function may offer important advantages for the user during insulin administration.

Analysis on clinical features of 106 type 2 diabetic patients complicated with insulin autoimmune syndrome

Objective To analyze the clinical features of type 2 diabetic patients with insulin autoimmune syndrome after treatment with exogenous insulin. Methods A total of 106 patients with type 2 diabetes diagnosed with exogenous insulin-related insulin autoimmune syndrome (EIAS) were included from September 2017 to March 2019 in the Department of Endocrinology, Zhongshan Hospital, Fudan University. The clinical data, physical examination, and laboratory examination results of patients were collected. Results Of the 106 patients, 84 (79.24%) used premixed human insulin or premixed insulin analogs, and 18 patients (16.98%) presented recurrent hypoglycemia. The arginine stimulation test showed that the median value of the baseline insulin was 73.40 (23.07-146.75) μU/ml, and the median ratio of 4 minute insulin to 0 minute insulin was 1.27 (1.03-1.85), with the mean of the ratio 1.72±1.47. The ratio of baseline insulin (μU/ml) to C-peptide (ng/ml) was 44.60 (14.92-87.93), with an average of 81.92±130.93. Taking the two-fold upper limit of fasting insulin reference value (49.8 μU/ml) as the cut-off point, the subjects were divided into insulin accumulation group (baseline insulin≥49.8 μU/ml) and insulin non-accumulation group (baseline insulin <49.8 μU/ml). Among the 66 patients in the insulin accumulation group, 14 patients had hypoglycemia (21.21%) and 4 patients in the insulin non-accumulation group presented hypoglycemia (10%). The ratio of 4 minute insulin to baseline insulin, ratio of baseline insulin to C-peptide, blood glucose level standard deviation (SDBG) and maximum blood glucose fluctuation amplitude (LAGE) in the insulin accumulation group were significantly higher than those in the insulin non-accumulation group (all P<0.05). Among 66 patients in the insulin accumulation group, 36 patients changed the type of insulin preparafion (insulin treatment group), 30 patients were changed from insulin to oral hypoglycemic agents (oral medication group). After treatment, both SDBG and LAGE in the two groups were significantly lower than before treatment (P<0.05). Conclusions With the aggravation of exogenous insulin accumulation, the fluctuation of blood glucose and the proportion of hypoglycemia were significantly increased. There was a characteristic change in islet function in patients with insulin autoimmune syndrome. After arginine stimulation, there was no significant peak of insulin secretion, showing a high-level curve. The baseline insulin/C-peptide ratio was significantly increased. The prognosis of EIAS patients is good after timely diagnosis and adjustment of treatment. Key words: Diabetes mellitus, type 2; Insulin autoantibody; Exogenous insulin-related insulin autoimmune syndrome

Self-management of type 2 diabetes mellitus utilizing technology based mobile medical assisted blood glucose management: Study protocol for a prospective, multi-center, observational study

IntroductionDiabetes mellitus is a major health concern globally as well as in China. Currently, the blood glucose (BG) control and patient outcome of diabetes are less than optimal, due to the poor adherence to established evidence-based treatment guidelines and low utilization of preventive care services by both providers and patients. Evidence suggest the benefit of mobile technology-based applications in improving BG monitoring and management in type 2 diabetes mellitus (T2DM). This study is designed to evaluate the effectiveness, safety and timeliness of the mobile internet technology in improving outpatients blood glucose self-management of Chinese T2DM. Methodsand Analysis: This is a prospective, single-arm, multi-center, observational study involving 250 hospitals across China. Patients aged ≥18 and ≤ 80 years with a diagnosis of T2DM and poor glycemic control, who were willing to receive premixed insulin analogues and could use their own WeChat account independently, were included in the study. The primary outcome of the study is to assess the benefit of programme based on change in hemoglobin A1c (HbA1c) from baseline to 3 months. Secondary outcomes included proportion of patients achieving HbA1c<7% at 3 months, change in fasting and postprandial glucose levels from baseline, incidence of hypoglycemia, frequency of self-monitoring blood glucose (SMBG), the patient behavior of BG monitoring on platform and the association of BG control with health care professionals (HCP)-patient interaction. The mobile based technology intervention can improve the HbA1c and BG levels in the patients receiving premixed insulin analogues and that the adherence of SMBG was increased and the incidence of hypoglycemia was decreased. Additionally, early detection of treatment-related hypoglycemia or other complications will contribute to timely therapeutic adjustments and lifestyle modifications under HCP's recommendations through the seamless HCP-patients interaction based on the mobile application. Ethics and disseminationThe study protocol was approved by the ethics committees from each study site according to the International Conference on Harmonization guidelines for Good Clinical Practice and conformed to Declaration of Helsinki. The results of the analyses will be shared with all the participating hospitals and will be published in peer-reviewed journals. No personal information will be included in the findings. RegistrationThis study was registered at chictr.org.cn (ChiCTR 1900021191).

The Effect of LM25 and LM50 on Hypoglycemia in Chinese T2DM Patients: Post Hoc Analysis of a Randomized Crossover Trial.

IntroductionTo investigate the safety of insulin lispro Mix 25 and 50 (LM25 and LM50) in hypoglycemia in patients with type 2 diabetes mellitus (T2DM).MethodsThis was a post hoc analysis of a phase IV, randomized, crossover clinical trial in Chinese patients with T2DM switching from premixed human insulin 70/30 (PHI70/30) to LM25 or LM50. Eighty-one subjects received a two-stage crossover protocol of either LM25 or LM50 twice daily for 16 weeks. Habitual diet was taken, and self-monitoring of blood glucose (SMBG) was performed throughout the study period. High-carbohydrate diet (HCD), high-fat diet (HFD) and habitual diet patterns were taken, and 72 h continuous glucose monitoring (CGM) was performed at the last 3 days of each treatment stage.ResultsThe frequencies of nocturnal hypoglycemia in LM50 were lower than those in LM25 under a Chinese habitual diet pattern. The related factors of hypoglycemia in patients with T2DM treated with a LM25 or LM50 regimen were the weight-based daily mean insulin dose and the type of combined oral hypoglycemic agents. Under both HCD and habitual diet patterns, the optimal cut point values of bedtime glucose predicting nocturnal hypoglycemia in LM50 were lower than those in LM25.ConclusionsThe risk of nocturnal hypoglycemia in the LM50 regimen was lower than that in the LM25 regimen under the HCD pattern, and the safety range of bedtime glucose for the LM50 regimen was wider than that of the LM25 regimen in Chinese T2DM patients. Premixed insulin analogs combined with acarbose were more helpful to reduce the incidence of hypoglycemia.Trial Registrationhttp://www.chictr.org.cn #ChiCTR-TTRCC-12002516.

Chronic Viral Hepatitis Signifies the Association of Premixed Insulin Analogues with Liver Cancer Risks: A Nationwide Population-Based Study.

This study sought to determine whether chronic hepatitis B or C would modify the association between insulin analogues and hepatocellular carcinoma (HCC) risks. We conducted a nationwide nested case-control study for HCC cases and matched controls from 2003 to 2013 among newly diagnosed type 2 diabetes patients on any antidiabetic agents in Taiwan before and after exclusion of chronic viral hepatitis, respectively. A total of 5832 and 1237 HCC cases were identified before and after exclusion of chronic viral hepatitis, respectively. Incident HCC risks were positively associated with any use of premixed insulin analogues (adjusted odds ratio (OR), 1.27; 95% CI 1.04 to 1.55) among total participants, especially among current users (adjusted OR, 1.45; 95% CI 1.12 to 1.89). However, the association between HCC occurrence and premixed insulin analogues diminished among participants without chronic viral hepatitis (adjusted OR, 1.35; 95% CI 0.92 to 1.98). We also observed a significant multiplicative interaction between chronic viral hepatitis and premixed insulin analogues on HCC risks (P = 0.010). Conclusions: Chronic viral hepatitis signifies the role of premixed insulin analogues in HCC oncogenesis. We recommend a closer liver surveillance among patients prescribed premixed insulin analogues with concomitant chronic viral hepatitis.

PDB131 INSULIN TREATMENT PATTERN, RESOURCE UTILIZATION AND COSTS IN CHINESE PATIENTS WITH TYPE 2 DIABETES MELLITUS INITIATED BASAL OR PREMIXED INSULIN ANALOGS AFTER INSULIN INTENSIFICATION

Hospitalized insulin intensification is a common practice to achieve better glycemic control for type 2 diabetes mellitus (T2DM) patients in China. This study aimed to assess insulin treatment pattern, resource utilization and costs for Chinese patients with T2DM initiating basal or premixed insulin analogs after hospitalized insulin intensification. Data were obtained from Tianjin Urban Employee Basic Medical Insurance claims database (2012-2015). T2DM patients aged ≥18 who initiated basal or premixed insulin analogs at discharge after hospitalized insulin intensification during 2013.01.01-2014.12.31 were included. Insulin treatment pattern (discontinuation/switching/intensification/maintenance), T2DM-related and all-cause health resource utilization and direct medical costs were examined during 12-month after discharge. Logistic, poisson and quantile regression models controlling for potential confounders were used to compare differences of resource utilization and costs between two groups. 724 patients initiating basal (N=188) and premixed (N=536) insulin analogs were included (mean[SD] age: 57.9[10.4] vs. 58.0[11.1], P=0.921; female: 46.3% vs. 38.8%, P=0.073), of which 57.4% and 50.6% (P=0.104) were also prescribed oral antidiabetic drugs at discharge. Insulin treatment pattern, of basal and premixed groups represented by discontinuation (16.0% vs. 24.8%), switching (5.9% vs. 4.7%), intensification (20.7% vs. 6.3%) and maintenance (57.4% vs. 64.2%) rates was different (P<0.001). T2DM-related hospitalization rates were similar in basal and premixed groups (19.7% vs. 20.0%, P=0.934). Basal group had more T2DM-related outpatient visits compared with premixed group (mean[SD]: 53.3[31.5] vs. 42.7[30.9], P<0.001). And the total T2DM-related and all-cause costs were also significantly higher in basal group than premixed group (T2DM-related: median[IQR]: CNY 17,445[11,840-25,023] vs. 12,909[7,085-21,061], P<0.001; all-cause: CNY 21,527[13,295-30,043] vs. 16,555[9,432-26,073], P<0.001). Similar trends were found in adjusted analyses. After hospitalized insulin intensification, Chinese T2DM patients initiating basal or premixed insulin analogs differ in their insulin treatment pattern, and patients initiating basal insulin analogs are associated with more outpatient visits and higher medical costs than premixed insulin analog initiators.

Contribution of BHG and PPHG to Overall Hyperglycemia in T2DM Patients Treated with LM25 and LM50: Post Hoc Analysis of a Randomized Crossover Trial.

IntroductionTo investigate the relative contribution rates of basal hyperglycemia (BHG) and postprandial hyperglycemia (PPHG) to overall hyperglycemia in patients with type 2 diabetes mellitus (T2DM) treated with insulin lispro mix 25 and 50 (LM25 and LM50) as evaluated by continuous glucose monitoring (CGM).MethodsEighty-one T2DM patients treated with premixed human insulin 70/30 (PHI70/30) were randomly divided into two groups and received a crossover protocol. In the first 16-week stage, one group received LM25 twice daily, the other group received LM50 twice daily. In the second 16-week stage, the two groups exchanged therapeutic regimen. Glycosylated hemoglobin (HbA1c) measurement and CGM were performed at enrollment and at the end of each treatment stage.ResultsBHG’s contribution rate increased with increasing HbA1c (from 34.5% to 60.8%). PPHG’s contribution rates in the LM50 regimen were significantly lower than those in LM25 and PHI70/30 regimens at HbA1c levels < 7.5%. Compared with LM50, LM25 shows a significant difference in reducing HbA1c in the subgroup with baseline HbA1c ≥ 8.5% (ΔHbA1c LM25 vs. LM50 − 0.6 ± 0.1% vs. 0.3 ± 0.1%, p < 0.05).ConclusionsFor T2DM patients treated with premixed insulin analogues, postprandial hyperglycemia played a major role in the subgroup of patients with HbA1c < 8.5%, while fasting hyperglycemia became the major contributor to overall hyperglycemia in the subgroup of patients with HbA1c ≥ 8.5%.Trial RegistrationChinese Clinical Trial Registry Identifier ChiCTR-TTRCC-12002516.FundingLilly Suzhou Pharmaceutical Co., Ltd. (Shanghai Branch, China) and National Key Program of Clinical Science of China (WBYZ2011-873).

A Real-World Anti-Diabetes Medication Cost Comparison Between Premixed Insulin Analogs and Long-Acting Insulin Analogs in Chinese Patients with Type 2 Diabetes: A Retrospective Database Analysis.

IntroductionTo assess and compare per-day anti-diabetic medication costs for Chinese type-2 diabetes mellitus (T2DM) insulin-naïve patients between those who initiated premixed insulin analogs (“premixed group”) and those who initiated long-acting insulin analogs (“long-acting group”).MethodsData were obtained from an electronic medical record database between 2010.01.01 and 2015.06.30 covering medical encounter records from all general hospitals in a district from Shanghai, China. Insulin-naïve T2DM patients who were aged ≥ 18 years, treated with an oral anti-diabetic drug (OAD) only during the baseline period (3 months prior to insulin initiation), and initiated premixed or long-acting insulin analogs were included. Patients were followed until index insulin discontinuation or 12 months after initiation, whichever came first. The t test and generalized linear models adjusting for propensity score (PS) (including baseline demographics, number of OAD classes, comorbidities, costs, and healthcare resource utilization) were used to examine the differences between the two insulin groups.ResultsA total of 570 and 185 patients were identified for the premixed and long-acting groups, with mean (SD) ages of 63.0 (12.8) and 61.1 (11.9) (P = 0.08) and male proportions of 47.4% and 51.4% (P = 0.35), respectively. During the baseline period, 19.3% of the premixed users had T2DM-related hospitalizations, while the rate was 12.4% in the long-acting group (P = 0.03). The mean number of T2DM-related outpatient visits was 0.98 and 1.23 for the premixed and long-acting groups, respectively (P = 0.07). During the follow-up period, the per-day insulin dose averaged 31.7 and 15.3 international units (IU) for the premixed and long-acting groups, respectively. Compared with the patients on premixed insulin, the mean per-day cost for patients on long-acting insulin was 37.3% higher [15.3 vs 11.2 Chinese yuan (RMB); mean difference (MD) (95% CI): 4.2 (3.2, 5.1)] for the overall anti-diabetes medication, 81.3% higher [3.3 vs 1.8 RMB; MD (95% CI): 1.5 (0.8, 2.2)] for OAD, and 28.6% higher [12.0 vs 9.3 RMB; MD (95% CI): 2.7 (2.1, 3.3)] for insulin. The results were consistent after adjusting for the PS.ConclusionAmong Chinese T2DM insulin-naïve patients, those who initiated premixed insulin had a lower per-day antidiabetic medication cost than those who initiated long-acting insulin.FundingLilly Suzhou Pharmaceutical Co. Ltd, China.

Original paper: Efficacy and safety analysis of insulin degludec/insulin aspart compared with biphasic insulin aspart 30: A phase 3, multicentre, international, open-label, randomised, treat-to-target trial in patients with type 2 diabetes fasting during Ramadan

AimsTo compare the efficacy and safety of insulin degludec/insulin aspart (IDegAsp) and biphasic insulin aspart 30 (BIAsp 30) before, during and after Ramadan in patients with type 2 diabetes mellitus (T2DM) who fasted during Ramadan. MethodsIn this multinational, randomised, treat-to-target trial, patients with T2DM who intended to fast and were on basal, pre- or self-mixed insulin ± oral antidiabetic drugs for ≥90 days were randomised (1:1) to IDegAsp twice daily (BID) or BIAsp 30 BID. Treatment period included pre-Ramadan treatment initiation (with insulin titration for 8–20 weeks), Ramadan (4 weeks) and post-Ramadan (4 weeks). Insulin doses were reduced by 30–50% for the pre-dawn meal (suhur) on the first day of Ramadan, and readjusted to the pre-Ramadan levels at the end of Ramadan. Hypoglycaemia was analysed as overall (severe or plasma glucose <3.1 mmol/L [56 mg/dL]), nocturnal (00:01–05:59) or severe (requiring assistance of another person). ResultsDuring the treatment period, IDegAsp (n = 131) had significantly lower overall and nocturnal hypoglycaemia rates with similar glycaemic efficacy, versus BIAsp 30 (n = 132). During Ramadan, despite achieving significantly lower pre-iftar (meal at sunset) self-measured plasma glucose (estimated treatment difference: −0.54 mmol/L [−1.02; −0.07]95% CI, p = .0247; post hoc) with similar overall glycaemic efficacy, IDegAsp showed significantly lower overall and nocturnal hypoglycaemia rates versus BIAsp 30. ConclusionsIDegAsp is a suitable therapeutic agent for patients who need insulin for sustained glucose control before, during and after Ramadan fasting, with a significantly lower risk of hypoglycaemia, versus BIAsp 30, an existing premixed insulin analogue.

Use of 50/50 Premixed Insulin Analogs in Type 2 Diabetes: Systematic Review and Clinical Recommendations.

IntroductionPremixed insulin analogs represent an alternative to basal or basal–bolus insulin regimens for the treatment of type 2 diabetes (T2D). “Low-mix” formulations with a low rapid-acting to long-acting analog ratio (e.g., 25/75) are commonly used, but 50/50 formulations (Mix50) may be more appropriate for some patients. We conducted a systematic literature review to assess the efficacy and safety of Mix50, compared with low-mix, basal, or basal–bolus therapy, for insulin initiation and intensification.MethodsMEDLINE, EMBASE, Cochrane Database of Systematic Reviews, ClinicalTrials.gov, LillyTrials.com, and NovoNordisk-trials.com were searched (11 or 13 Dec 2016) using terms for T2D, premixed insulin analogs, and/or Mix50. Studies (randomized, nonrandomized, or observational; English only) comparing Mix50 with other insulins (except human) and reporting key efficacy [glycated hemoglobin (HbA1c), fasting and postprandial glucose] and/or safety (hypoglycemia, weight gain) outcomes were eligible for inclusion. Narrative reviews, letters, editorials, and conference abstracts were excluded. Risk of bias in randomized trials was assessed using the Cochrane tool.ResultsMEDLINE and EMBASE searches identified 716 unique studies, of which 32 met inclusion criteria. An additional three studies were identified in the other databases. All 19 randomized trials except one were open label; risk of other biases was generally low. Although not conclusive, the evidence suggests that Mix50 may provide better glycemic control (HbA1c reduction) and, particularly, postprandial glucose reduction in certain patients, such as those with high carbohydrate diets and Asian patients, than low-mix and basal therapy. Based on this evidence and our experience, we provide clinical guidance on factors to consider when deciding whether Mix50 is appropriate for individual patients.ConclusionsMix50 may be more suitable than low-mix therapy for certain patients. Clinicians should consider not only efficacy and safety but also patient characteristics and preferences when tailoring insulin treatment to individuals with T2D.FundingEli Lilly.Electronic supplementary materialThe online version of this article (doi:10.1007/s13300-017-0328-6) contains supplementary material, which is available to authorized users.

Efficacy and safety of premixed insulin analogs in Asian patients with type 2 diabetes: A systematic review.

Aims/IntroductionThe primary aim of this systematic review was to provide an overview of the efficacy and safety of premixed insulin analogs in Asians, specifically East Asians, with type 2 diabetes.Material and MethodsThe MEDLINE, Embase, Cochrane Library and ClinicalTrials.gov databases were searched from 1 January 1995 to 26 November 2015. Randomized controlled trials involving East Asians with type 2 diabetes treated with any premixed insulin analog were included. Major comparator treatments were basal insulin and basal–bolus insulin. Comparisons were also made between East Asian and Caucasian patients. The primary efficacy outcome was glycated hemoglobin change from baseline to end‐point. The primary safety outcome was the incidence of hypoglycemia.ResultsA total of 21 studies were included; most (n = 14) were carried out in China or Japan. The duration of treatment ranged from 12 to 48 weeks. The glycated hemoglobin mean/least squares mean change from baseline to end‐point after treatment with premixed insulin analogs ranged from −0.12 to −4.2% (improvement was generally more pronounced with insulin initiation vs intensification). The incidence of hypoglycemia ranged from 8.3 to 72.0% in most studies, with the variability reflecting the definition of hypoglycemia used. Efficacy and safety outcomes for premixed insulin analogs were generally similar to those for basal or basal–bolus insulin. Limited evidence suggests that dosing, efficacy and safety profiles might differ slightly between East Asian and Caucasians receiving premixed insulin analogs.ConclusionsThese results support the current use of premixed insulin analogs for managing East Asian patients with type 2 diabetes.

Evaluation of a Premixed Insulin Analog Suspension in Japanese People with Type 2 Diabetes and the Clinical Importance of Improved Injection Techniques: A Cross-Sectional Pilot Study.

IntroductionPatients with type 2 diabetes, who live in Asian countries, often use premixed insulin analogs. However, if these solutions are insufficiently mixed prior to use, patients will receive inaccurate doses of intermediate- and/or short-acting insulin, which could affect diabetes control. This study aimed to determine whether insulin users were correctly resuspending premixed insulin analog solutions prior to use.MethodsWe investigated whether Japanese patients with type 2 diabetes were correctly resuspending their premixed insulin analog solutions by assessing the optical densities (ODs) of the solutions.ResultsAmong 476 patients who used premixed insulin analogs, we found that the ODs of residual insulin differed significantly from the control values, particularly for high-mix insulin suspensions.ConclusionOur findings suggest that patients should be educated about the importance of properly resuspending these insulin analog solutions prior to use.Trial RegistrationUniversity Hospital Medical Information Network (UMIN No. 000022329).

Switching from Biphasic Human Insulin to Premix Insulin Analogs: A Review of the Evidence Regarding Quality of Life and Adherence to Medication in Type 2 Diabetes Mellitus.

Novo Nordisk.