Objective. Compared with other insulin analogues, insulin detemir induces less weight gain. This study investigated whether this effect was achieved by influencing the hypothalamic appetite regulators neuropeptide Y (NPY) and galanin (GAL). Methods. Type 2 diabetic rat models were established with a high-fat diet and intraperitoneal injection of STZ. All rats were divided into NC, DM, DM

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Insulin detemir causes lesser weight gain in comparison to insulin glargine: role on hypothalamic NPY and galanin.

Various data have demonstrated inadequate glycemic control amongst Asians with type 2 diabetes mellitus (T2DM), possibly on account of suboptimal titration of basal insulin—an issue which needs to be further examined. Here we review the available global and Asia-specific data on titration of basal insulin, with a focus on the use of insulin glargine 100 U/mL (Gla-100). We also discuss clinical evidence on the efficacy and safety of titrating Gla-100, different approaches to titration, including some of the latest technological advancements, and guidance on the titration of basal insulin from international and local Asian guidelines. The authors also provide their recommendations for the initiation and titration of basal insulin for Asian populations. Discussion of the data included in this review and in relation to the authors’ clinical experience with treating T2DM in Asian patients is also included. Briefly, clinical studies demonstrate the achievement of adequate glycemic control in adults with T2DM through titration of Gla-100. However, studies investigating approaches to titration, specifically in Asian populations, are lacking and need to be conducted. Given that the management of insulin therapy is a multidisciplinary team effort involving endocrinologists, primary care physicians, nurse educators, and patients, greater resources and education targeted at these groups are needed regarding the optimal titration of basal insulin. Technological advancements in the form of mobile or web-based applications for automated dose adjustment can aid different stakeholders in optimizing the dose of basal insulin, enabling a larger number of patients in Asia to reach their target glycemic goals with improved outcomes.

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Optimizing Glycemic Control Through Titration of Insulin Glargine 100 U/mL: A Review of Current and Future Approaches with a Focus on Asian Populations

Background: Gluconeogenesis and renal glucose excretion in kidneys both play an important role in glucose homeostasis. Sodium-glucose cotransporter (SGLT2), coded by the SLC5A2 gene is responsible for reabsorption up to 99% of the filtered glucose in proximal tubules. SLC5A2 genetic polymorphisms were suggested to influence glucose homeostasis. We investigated if common SLC5A2 rs9934336 polymorphism influences glycemic control and risk for macro or microvascular complications in Slovenian type 2 diabetes (T2D) patients. Methods: All 181 clinically well characterized T2D patients were genotyped for SLC5A2 rs9934336 G>A polymorphism. Associations with glycemic control and T2D complications were assessed with nonparametric tests and logistic regression. Results: SLC5A2 rs9934336 was significantly associated with increased fasting blood glucose levels (P<0.001) and HbA1c levels under the dominant genetic model (P=0.030). After adjustment for T2D duration, significantly higher risk for diabetic retinopathy was present in carriers of at least one polymorphic SLC5A2 rs9934336 A allele compared to non-carriers (OR=7.62; 95%CI=1.65-35.28; P=0.009). Conclusions: Our pilot study suggests an important role of SLC5A2 polymorphisms in the physiologic process of glucose reabsorption in kidneys in T2D patients. This is also the first report on the association between SLC5A2 polymorphism and diabetic retinopathy.

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Genetic variability in sodium-glucose cotransporter 2 influences glycemic control and risk for diabetic retinopathy in type 2 diabetes patients.

Purpose To compare the immunogenicity and efficacy of insulin glargine biosimilar Ezelin (EZL) versus originator insulin glargine Lantus (LAN) as a reference basal insulin in patients with type 2 diabetes (T2D). Patients and methods This was a randomized, multicenter, open-label, 24-week study in insulin-naive patients with T2D, with HbA1c of >7.0%. We randomly assigned 133 eligible patients to receive either EZL or LAN. Baseline characteristics, including insulin autoantibody (IAA), zinc transporter 8 (ZnT8) antibody, HbA1C, fasting plasma glucose (FPG), 2-hour postprandial plasma glucose (2hPPG), AST, ALT, BUN, eGFR, and oral antidiabetic drugs, were obtained before starting insulin treatment. After starting treatment, insulin dose was titrated to achieve FPG target along with oral antidiabetic drugs. Patients were given home glucometer and assisted to record plasma glucose measurement and adverse event (AE). Every month, patients came to the diabetes clinic and performed a regular physical examination and intensifying treatment if needed. Out of the 133 randomized patients, only 122 completed the study and can be examined for their IAA and ZnT8 after 6 months of treatment. The study was registered in clinicaltrials.gov, NCT03352674. Results There is a similar proportion of patients with changes of IAA from baseline: 1 out of 58 (1.7%) patients receiving EZL versus 1 out of 64 (1.6%) patients receiving LAN (p = 1.000). One patient in the EZL group (1.7%) versus none in the LAN group experienced a change of ZnT8 antibody from baseline. Similar glucose control in EZL versus LAN was determined by the change in HbA1c, FPG, and 2hPPG (-2.0%, -67.46 mg/dL, and -76.51 mg/dL in the EZL group versus -1.7%, -58.11 mg/dL, and -70.03 mg/dL in the LAN group). There were six events of documented hypoglycemia in the EZL group versus five events in the LAN group. No patients experienced diabetic ketoacidosis during the study. Conclusion Overall, insulin glargine biosimilar EZL and originator insulin glargine LAN have shown a similar immunogenicity profile, as well as efficacy in providing glucose control and safety findings in T2D populations.

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Immunogenicity and Efficacy of Insulin Glargine Biosimilar Ezelin versus Originator Insulin Glargine in Patients with Type 2 Diabetes.

Diabetes treatment requires specialized multi-professional teams, supplies for blood glucose monitoring and training for self-injections of human insulin or insulin analogues. The State Health Secretariat of the Federal District (SHS-FD) has dispensed insulin analogues by means of clinical validated protocols since 2004. However, data on outcomes of follow-up are still unknown. To evaluate the results of glycated hemoglobin (HbA1c) among diabetic patients treated with insulin analogues. It is a retrospective cohort study involving data of type 1(DM1) and type 2 diabetes (DM2) patients 18 years old and above who were registered to participate at the insulin analogues dispense program of the SHS-FD. Evaluation of criteria of insulin treatment continuity was based on HbA1c values achieved in the follow-up period: in the target, 65 years), more than three medical appointments in the follow-up and lower mean HbA1c in the patient selection for inclusion criteria in the dispense program (p < 0.05). The low number of patients using insulin analogues in the target group, considered to be in good control, implies the need to reevaluate both level of patients self-care knowledge and glucose monitoring prior their inclusion in the insulin analogue dispense program. Reinforcement and training of health professional teams in enrollment procedures should be on mandatory basis to avoid protocol failure or deviations.

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Results of glycated hemoglobin during treatment with insulin analogues dispensed in the public health system of Federal District in Brazil.

Purpose: Optimizing glycemic control in patients with type 2 diabetes mellitus (T2DM) not controlled with ≥ 1 oral antidiabetes drugs (OADs) is challenging. Many therapeutic options exist; however, data comparing the effectiveness of different strategies are lacking for the management of patients with T2DM. Our study aim was to provide comparative data on efficacy and hypoglycemia when initiating insulin glargine (glargine) versus alternative treatment options (not including the newest antidiabetes agents, glucagon-like peptide [GLP]-1 receptor agonists, dipeptidyl peptidase [DPP]-4 inhibitors or sodium-glucose linked transporter [SGLT]-2 inhibitors) in insulin-naive patients with T2DM who remained uncontrolled with OADs. Methods: Patient-level data were pooled from 9 randomized controlled trials of ≥ 24 weeks duration with comparable patient populations. The effect of adding glargine was compared with intensification of lifestyle interventions or OADs, addition of neutral protamine Hagedorn (NPH)...

Ling Gao

Papers

Influence of Baseline Glycemia on Outcomes With Insulin Glargine Use in Patients Uncontrolled on Oral Agents