The first and only combination of basal and prandial insulin analogs degludec and aspart: the position of Russian endocrinologists

Insulin therapy for diabetes mellitus is the most effective way to control glycemia with the progression of the disease and the ineffectiveness of other sugar-lowering drugs. At the same time, the existing limitations of traditional insulin preparations, along with increasing attention to the individualized treatment of this disease, are pushing developers to create drugs that most closely reproduce the effect of natural human insulin. In this regard, the appearance of a combination of insulin analogs, the action profile of which practically imitates insulin secretion by a healthy pancreas, presents new possibilities in the treatment of diabetes mellitus. Insulin degludec / insulin aspart (IDegAsp, Ryzodeg®, Novo Nordisk, Denmark) is the first and only soluble combination preparation containing 70% of the ultra-long-acting insulin analogue degludec and 30% of the ultra-short-acting insulin analogue aspart in one injection, which meets the need for both basal and prandial insulin. The combined drug has nothing in common with traditional mixed insulin preparations (both human and analog) and provides doctors and patients with significant advantages over the latter. The article presents the position of Russian experts-diabetologists with extensive experience in the use of IDegAsp regarding the role and place of the drug in real clinical practice. Data from real clinical practice confirm that IDegAsp is a reasonable choice for starting and intensifying insulin therapy for type 2 diabetes mellitus when basal and prandial glycemic control is required. The use of the drug is most appropriate in patients who are on basal, biphasic, basal-plus/basal-bolus regimens and who do not achieve the goals of glycemic control during prior therapy. One of the leading reasons for choosing IDegAsp may also be a lower risk of developing hypoglycemia compared to insulin analogues of previous generations — biphasic insulin aspart and basal insulin glargine 100 U/ml. In addition, IDegAsp is a simple, flexible and safe insulin therapy for patients on premix therapy and basal-plus/basis-bolus regimens who require basal and prandial glycemic control. IDegAsp is a simple, flexible and safe insulin therapy. The greatest benefit of this drug use can be obtained by patients for whom adherence to a complex therapy regimen is difficult (the elderly, with cognitive impairment, after a stroke, with dementia), as well as patients who have an active lifestyle, accompanied by irregular food intake. It is important to note that since January 1, 2021, there is no need for a decision by a special medical commission to prescribe (IDegAsp) Ryzodeg®. This fact, as well as a significant price reduction at the end of 2020, opens up broader prospects for using the drug in the routine practice of a Russian endocrinologist.

Insulin Injection Technique is Negatively Correlate to Short- and Long-run Glycemic Control in Type 2 Diabetic Patients with Long-Acting Insulin Analogue

Objective: To observe the effects of insulin injection technique (IT) on short- or long-run glycemic control in type 2 diabetic patients (T2D) with long-acting insulin analogue. Methods: This was a single-center, cross-over, observational and open-labled study. Patients with T2D receiving long-acting insulin analogue insulin were enrolled as inpatients. The study period lasting for 5 days including a 1-day screen period and 4-day continuous glucose monitoring (CGM) period. During CGM period, patients injected insulin themselves from day 1 to day 2, and patient’s insulin IT was given by two independent specialist nurses, with insulin injected by nurses from day 3 to day 4. The primary endpoint was the correlation between the insulin IT and the mean amplitude of glycemic excursion (MAGE). Results: A total of 60 diabetic inpatients were recruited and completed the study. The mean score of patients’ insulin IT of patients was lower than that of nurses (p<0.05). We observed that the MAGE value was significant different between the two injections period (P<0.05), and needle reuse and rotation of injection site were negatively correlated to MAGE and HbA1c values, respectively. Conclusion: Insulin IT was negatively correlation to short- or long-run glycemic control in T2D patients with long-acting insulin analogue therapy.

Combination Therapy With Premixed & Basal Insulin Analogues in Asian Indians With Type 2 Diabetes

Many individuals with type 2 diabetes (T2DM) eventually need insulin for better glycaemic control. Different insulin regimens like basal, premixed, basal plus, split mixed and basal bolus are used in T2DM management. There is not much literature on a combination of premixed insulin in the morning along with basal insulin at night. Such a regimen is preferred by people with T2DM, who do not want to take an afternoon insulin dose due to inconvenience. To study the effect of a premixed insulin given in the morning and long acting basal insulin analogue given at night in T2DM subjects, we looked into this combination. We performed a retrospective study to look into the effects of premixed and basal insulin analogue combination in patients with T2DM (in addition to oral antidiabetic agents). From the diabetes electronic medical records of a tertiary care hospital for diabetes at Chennai in South India, 648 patients on premixed and basal insulin analogue combination, who came for a follow-up visit were included in the final analysis. Baseline characteristics included body weight, BMI, blood pressure, fasting lipid profile, fasting and post prandial plasma glucose and HbA1c were analysed at baseline, and a change in the parameters was studied at the first follow up visit between 5 to 7 months. Mean age of the study population was 60.7± 13.1 years with mean diabetes duration of 20.5 ± 8.0 years. Out of 648 patients included, three fifths were male. Statistically significant improvement was observed in body weight, BMI, HbA1c, systolic blood pressure, lipid profile, fasting blood sugars (P &lt; 0.001) and post prandial blood sugars (P= 0.005) in comparison to baseline values. Significant reduction in HbA1c (1.7 %, p &lt; 0.0001) was observed in those with in the highest tertile of HbA1c (11.3 ± 1.0 %) in comparison to the baseline values. At follow up, nearly a third of study subjects achieved a HbA1c target of &lt; 8% (30.1 % vs 18.4 0%, p =0.0005) in comparison to the baseline values. 28.7 % patients on combination therapy achieved a fasting blood sugar value of &lt; 130 mg/dl at follow up compared to 18.2 % patients at baseline (p &lt;.0001). Similarly, 22 % of the patients on combination therapy also achieved post prandial blood sugars of &lt;180 mg/dl at follow up, compared to 12.2 % (P&lt;.0001) at baseline. This study shows that in T2DM subjects, a simple regimen of premixed and basal insulin analogue combination helps in improving the glycaemic control.

Different Gestational Diabetes Phenotypes: Which Insulin Regimen Fits Better?

ObjectiveMaternal characteristics and OGTT values of pregnancies complicated by gestational diabetes mellitus (GDM) were evaluated according to treatment strategies. The goal was to identify different maternal phenotypes in order to predict the appropriate treatment strategy.MethodsWe conducted a retrospective study among 1,974 pregnant women followed up for GDM in a tertiary referral hospital for high-risk pregnancies (Careggi University Hospital, Florence, Italy) from 2013 to 2018. We compared nutritional therapy (NT) alone (n = 962) versus NT and insulin analogues (n = 1,012) group. Then, we focused on different insulin analogues groups: long acting (D), rapid acting (R), both D and R. We compared maternal characteristics of the three groups, detecting which factors may predict the use of rapid or long-acting insulin analogue alone versus combined therapy.ResultsAmong women included in the analysis, 51.3% of them needed insulin therapy for glycemic control: 61.8% D, 28.3% combined D and R, and 9.9% R alone. Age &gt;35 years, pre-pregnancy BMI &gt;30, family history of diabetes, previous GDM, altered fasting plasma glucose (FPG), hypothyroidism, and assisted reproductive technologies (ART) were identified as maternal variables significantly associated with the need of insulin therapy. Altered 1-h and 2-h glucose plasma glucose level at OGTT, age &gt;35 years, and previous GDM were found as independent predicting factors for the use of combined therapy with rapid and long acting analogues for glycemic control. On the contrary, pre-pregnancy BMI &lt;25 and normal fasting plasma glucose values at OGTT were found to be significantly associated to the use of rapid insulin analogue only.ConclusionA number of maternal and metabolic variables may be identified at the diagnosis of GDM, in order to identify different GDM phenotypes requiring a personalized treatment for glycemic control.

A nationwide cohort study for comparative vascular safety of long-acting insulin analogue versus intermediate-acting human insulin in type 2 diabetes

Little is known about the comparative vascular safety of basal insulins (intermediate-acting human insulin [IAHI] or long-acting insulin analogue [LAIA]) in type 2 diabetes (T2D). This study sought to examine the vascular and hypoglycemic effects associated with IAHI versus LAIA in real-world patients with T2D. We utilized Taiwan’s National Health Insurance Research Database to identify T2D patients who stably used IAHI (N = 11,521) or LAIA (N = 37,651) in the period 2004–2012. A rigorous three-step matching algorithm that considered the initiation date of basal insulin, previous exposure of antidiabetic treatments, comorbidities, diabetes severity and complications, and concomitant medications was applied to achieve the between-group comparability. Study outcomes, including cardiovascular diseases (CVDs), microvascular diseases (MVDs), and hypoglycemia, were assessed up to the end of 2013. Compared with LAIA, the use of IAHI was associated with greater risks of composite CVDs (adjusted hazard ratio [aHR]: 1.79; 95% confidence interval [CI] 1.20–2.67) and hospitalized hypoglycemia (aHR: 1.82; 95% CI 1.51–2.20), but a lower risk of composite MVDs (aHR: 0.88; 95% CI 0.84–0.91). Subgroup and sensitivity analyses showed a consistent trend of results with that in the primary analyses. In summary, although the use of IAHI versus LAIA among T2D patients in usual practice may be associated with a lower risk of MVDs, strategies should be optimized for minimizing the risks of hypoglycemia and CVDs in this population.

Cost Excursion Study of Various Insulin Preparations Available in India

Introduction: Poor drug compliance affects clinical outcome and increases healthcare costs in various disease setting. Several type II diabetes mellitus patients, not controlled on oral hypoglycaemics eventually require insulin therapy. Antidiabetic treatment is to be taken lifelong and in such a setting insulin price variation imposes a huge economic burden on poor diabetic patients. Moderating drug cost is associated with improved adherence to the medication regimen. Aim: To study the variation in cost amongst various brands of insulin analogues. Materials and Methods: This was an observational, cross-sectional study. Data regarding the 116 formulations and cost of 18 types of insulin preparations was collected from sources like Current Index of Medical Specialties (CIMS), National Pharmaceutical Pricing Authority (NPPA), Government of India official website (https://nppaimis.nic.in/nppaprice/pharmasahidaamweb.aspx) and compared with its lowest counterpart. The cost ratio and percentage cost variation was analysed and expressed as percentages. Results: This study showed a noticeable variation in the prices of insulin analogues. The highest percentage of cost variation was found for Insulin (Highly Purified) Zinc-40 IU (135.17%), followed by Insulin (Analogue) Glargine-100 IU (109.31%). The lowest percentage were for: Insulin (Human-Isophane Recombinant)-40 IU (1.40%), and Insulin (Analogue) Aspart- 100 IU (6.26%). Conclusion: A noticeable variation in cost prices was observed especially in commonly used intermediate acting insulin that help basal glycaemic control. Similarly, the lowest variation was observed with recombinant counterparts as an effect of pre-existing high prices of each. Need for vital medication like insulin at affordable costs has incited national and global efforts to make it cheaper and accessible to maximum beneficiaries.