Enhancing Choices Regarding the Administration of Insulin Among Patients With Diabetes Requiring Insulin Across Countries and Implications for Future Care

There are a number of ongoing developments to improve the care of patients with diabetes across countries given its growing burden. Recent developments include new oral medicines to reduce cardiovascular events and death. They also include new modes to improve insulin administration to enhance adherence and subsequent patient management thereby reducing hypoglycaemia and improving long-term outcomes. In the case of insulins, this includes long-acting insulin analogues as well as continuous glucose monitoring (CGM) systems and continuous subcutaneous insulin infusion systems, combined with sensor-augmented pump therapy and potentially hybrid closed-loops. The benefits of such systems have been endorsed by endocrine societies and governments in patients with Type 1 diabetes whose HbA1c levels are not currently being optimised. However, there are concerns with the low use of such systems across higher-income countries, exacerbated by their higher costs, despite studies suggesting their cost-effectiveness ratios are within accepted limits. This is inconsistent in higher-income countries when compared with reimbursement and funding decisions for new high-priced medicines for cancer and orphan diseases, with often limited benefits, given the burden of multiple daily insulin injections coupled with the need for constant monitoring. This situation is different among patients and governments in low- and low-middle income countries struggling to fund standard insulins and the routine monitoring of HbA1c levels. The first priority in these countries is to address these priority issues before funding more expensive forms of insulin and associated devices. Greater patient involvement in treatment decisions, transparency in decision making, and evidence-based investment decisions should help to address such concerns in the future.

Effect of Continuous Subcutaneous Injection of Insulin Analogues in Pregnant Women with Diabetes Mellitus Complicated with Ketoacidosis

Objective. To investigate the clinical effect of continuous subcutaneous injection of insulin analogues in pregnant women with diabetes mellitus complicated with ketoacidosis. Methods. A total of 92 pregnant patients with diabetes mellitus complicated with ketoacidosis from June 2014 to January 2021 were selected. All patients were randomly divided into an observation group and control group according to the method of random number. The control group received intravenous infusion of insulin, and the observation group received continuous subcutaneous infusion of quick-acting insulin analogues. The clinical effects of the two groups were observed. Results. The time needed to control blood glucose <13.8 mmol/L, the amount of insulin needed to control blood glucose <13.8 mmol/L, the time needed to correct DKA, and the amount of insulin needed to correct DKA in the observation group were significantly less than those in the control group ( P < 0.05 ). Compared with the control group, the average occurrence times of hypoglycemia, the length of stay, the total amount of insulin in hospital, and the total amount of insulin used during pregnancy in the observation group were significantly less than those in the control group ( P < 0.05 ). The values of SCr, CRP, BUN, arterial blood gas pH, and adiponectin in the two groups were significantly improved as compared with those before treatment, and the improvement in the observation group was significantly better than that in the control group ( P < 0.05 ). After treatment, the fasting blood glucose, 2-hour postprandial blood glucose, carbon dioxide binding capacity, and glycosylated hemoglobin in the experimental group were significantly better than those in the routine group, and the difference was statistically significant ( P < 0.05 ). Conclusion. Continuous subcutaneous injection of insulin analogues is effective in the treatment of diabetic patients with ketoacidosis, which can effectively improve blood glucose, carbon dioxide binding capacity, and glycosylated hemoglobin and accelerate the negative conversion of urinary ketone body. It is worth popularizing to reduce the occurrence of hypoglycemia and the dose of insulin and shorten the time of hospitalization.

Does all the evidence say that insulin analogues are more effective than human insulins?

Currently, a large amount of data has been accumulated to compare recombinant human insulin with insulin analogues, including meta-analyzes of comparative efficacy and safety, as well as cost-effectiveness data and data on the possible carcinogenicity of new products. Insulin treatment is a necessity for some people with diabetes mellitus (DM) due to the need to maintain optimal blood glucose levels. The authors emphasize the need to keep in mind that new insulin drugs are much more expensive, which may limit their use. Factors such as the effectiveness of treatment, its safety, and patient satisfaction should be taken into account when deciding on the choice of therapy, but the cost of treatment cannot be ignored, given that it is usually reimbursable from the budget. In this regard, insulin therapy should be individually selected taking into account the needs of patients, treatment goals, safety, and cost. The authors propose an analysis of these data on the feasibility of using insulin analogues in comparison with recombinant human insulin for patients with type 1 diabetes and patients with type 2 diabetes and their effectiveness in both types of diabetes. A reasonable policy for the use of insulin therapy should be developed based on available clinical data based on comparative studies in different groups of diabetics and comprehensive analysis of economic data. The feasibility of a new drug should be evaluated and regularly reviewed in light of the practical results of its use in clinical practice. It is also necessary to regularly conduct a retrospective economic analysis to assess the pharmacoeconomic benefits. All of these steps should assist decision-makers and regulators in implementing effective national programs to develop new effective insulin procurement systems.

Retrospective trial of long acting analogues detemir and degludec usage in children and adolescents to overcome glucose variability caused by dawn phenomenon and reverse dawn phenomenon

Backgraund: Children with type 1 diabetes mellitus (T1DM) need more insulin late in the evening (reverse dawn phenomenon (RDP)), and adolescents need more insulin yearly in the morning (dawn phenomenon (DP)); these cause blood glucose variability. Modern long acting insulin analogues allow to achieve satisfactory glycemic control.Aims: To study the characteristics of insulin therapy in children and adolescents with T1DM using insulin analogues detemir and degludec to overcome blood glucose variability caused by DP and RDP in different age periods.Materials and methods: We analyzed medical documents of 200 patients using detemir, admitted to pediatric endocrinology department in 2013–2019, at mean age 9.0 years (5.4; 13.0), with T1DM for 1.3 years (0.5; 3.0); and medical documents of 50 patients switched to degludec in 2018–2019 at mean age 12.0 years (10.5; 14.5) with T1DM for 3.0 years (1.5; 6.0). Before degludec they were on intensive insulin therapy with glargine (22), detemir (26), or insulin pump (2); 16 patients (32%) presented with clinical characteristics of DP, and 5 (10%) — RDP.Results: 67 children of 108 (62%) aged 1–9 years had redistribution of detemir doses to daytime; 58 adolescents of 92 (63%) aged 10–17 лет — to nighttime. Patients switched to degludec demonstrated decrease in HbA1с from 8.7% (7.8; 9.9) to 8.0% (7.4; 9.0) (р<0.001); fasting blood glucose from 9.8 mmol/l (7.4; 11.7) to 7.7 mmol/l (6.4; 8.6) (р<0.001); within-day variability from 35.2% (31.6; 40.9) to 23.5% (19.7; 28.6) (р<0.001); daily insulin dose from 0.98 U/kg/day (0.82; 1.14) to 0.87 U/kg/day (0.75; 1.07) (р=0.002). Sub-groups of patients with DP and RDP demonstrated decrease in fasting blood glucose (from 11.5 mmol/l (9.8; 13.8) to 7.5 mmol/l (6.6; 9.1) (р<0.001)), and late evening blood glucose (from 11.0 mmol/l (10.2; 11.2) to 8.0 mmol/l (6.7; 9.5) (р= 0.03)) correspondently. Achieved levels of glycemic control did not differ between sub-groups of patients initially using glargine or detemir.Conclusions: Compensation of T1DM may be complicated due to DP and RDP. Switching to degludec allowed to achieve better glycemic control and lowering of blood glucose variability caused by DP and DRP.

Technological Developments and Quality of Life in Type 1 Diabetes Mellitus Patients: A Review of the Modern Insulin Analogues, Continuous Glucose Monitoring and Insulin Pump Therapy

Background: Type 1 Diabetes Mellitus (T1DM) is a chronic autoimmune disease, which is characterized by an increased prevalence worldwide, which, in fact, tends to take extensive dimensions. The recent rapid development of science and technology has significantly contributed to the improvement of the management of type 1 diabetes mellitus, both in achieving the required euglycaemic regulation and reducing the psychological burden associated with the disease, consequently improving the quality of life of the patients with type 1 diabetes mellitus. Methods: A literature review from 2010, related to the contribution of the modern insulin analogues, continuous glucose monitoring and the insulin pump, was performed using Scopus, ScienceDirect and PubMed databases. Results: Studies included in the review support a direct and indirect association of technological innovations with the quality of life. The use of type 1 diabetes mellitus technology was negatively associated with the frequency of the hypoglycaemias and the value of the glycosylated hemoglobin, while at the same time, the development and use of the related technology were highly associated with an improvement in the quality of life. Conclusion: Patients’ quality of life is an indicator of the management of type 1 diabetes mellitus, and it is just as important as glycaemic regulation. Through this review, it was concluded that a better quality of life of T1DM patients was associated with the improvement of glycosylated hemoglobin and hypoglycemic episodes.

Utilisation Trend of Long-Acting Insulin Analogues including Biosimilars across Europe: Findings and Implications

Background. Diabetes mellitus rates and associated costs continue to rise across Europe enhancing health authority focus on its management. The risk of complications is enhanced by poor glycaemic control, with long-acting insulin analogues developed to reduce hypoglycaemia and improve patient convenience. There are concerns though with their considerably higher costs, but moderated by reductions in complications and associated costs. Biosimilars can help further reduce costs. However, to date, price reductions for biosimilar insulin glargine appear limited. In addition, the originator company has switched promotional efforts to more concentrated patented formulations to reduce the impact of biosimilars. There are also concerns with different devices between the manufacturers. As a result, there is a need to assess current utilisation rates for insulins, especially long-acting insulin analogues and biosimilars, and the rationale for patterns seen, among multiple European countries to provide future direction. Methodology. Health authority databases are examined to assess utilisation and expenditure patterns for insulins, including biosimilar insulin glargine. Explanations for patterns seen were provided by senior-level personnel. Results. Typically increasing use of long-acting insulin analogues across Europe including both Western and Central and Eastern European countries reflects perceived patient benefits despite higher prices. However, activities by the originator company to switch patients to more concentrated insulin glargine coupled with lowering prices towards biosimilars have limited biosimilar uptake, with biosimilars not currently launched in a minority of European countries. A number of activities were identified to address this. Enhancing the attractiveness of the biosimilar insulin market is essential to encourage other biosimilar manufacturers to enter the market as more long-acting insulin analogues lose their patents to benefit all key stakeholder groups. Conclusions. There are concerns with the availability and use of insulin glargine biosimilars among European countries despite lower costs. This can be addressed.

Applying Historical Data in a Nonlinear Mixed-Effects Model Can Reduce the Number of Control Rats Required for Calculation of The Relative Potency of Insulin Analogues

This paper examines how to reduce the number of control animals in preclinical hyperinsulemic glucose clamp studies if we make use of information on historical studies. A data set consisting of 59 studies in rats to investigate new insulin analogues for diabetics, collected in the years 2000 to 2015, is analysed. A simulation experiment is performed based on a carefully built nonlinear mixed-effects model including historical information, comparing results (for the relative log-potency) with the standard approach ignoring previous studies. We find that by including historical information in the form of the mixed-effects model proposed, we can to remove between 23% and 51% of the control rats in the two studies looked closely upon to get the same level of precision on the relative log-potency as in the standard analysis. How to incorporate the historical information in the form of the mixed-effects model is discussed, where both a meta approach as well as a Bayesian approach are suggested. The conclusions are similar for the two approaches, and therefore, we conclude that the inclusion of historical information is beneficial in regard to using fewer control rats.