A randomized pharmacokinetic and pharmacodynamic trial of two regular human insulins demonstrates bioequivalence in type 1 diabetes and availability of biosimilar insulin may improve access to this medication.

AIMS: To compare the pharmacokinetic (PK) and pharmacodynamic (PD) effects and safety of therapeutic dosages of a regular insulin (experimental drug) produced by Bioton S.A. (Warsaw, Poland) versus Humulin® R, a regular insulin (reference drug) produced by Eli Lilly (Indianapolis, Indiana). MATERIALS AND METHODS: In a single-centre, randomized, double-blinded phase 1 crossover study, we used the manual euglycaemic clamp technique to compare PK and PD profiles between single subcutaneous doses (0.3 units/kg) of the two regular insulins in participants with type 1 diabetes (T1DM) with a washout period of 14 (± 7) days between tests. RESULTS: We evaluated 56 participants. The mean participant age and body mass index were 32.9 years and 22.9 kg/m2 , respectively. The ratios (experimental/reference) of the geometric means of maximum plasma insulin concentration and for plasma insulin area under the curve (AUC) were 0.909 (90% confidence interval [CI] 0.822-1.01) and 0.993 (90% CI 0.944-1.04), respectively. The ratios of the geometric means of maximum glucose infusion rate (GIR) and for GIR AUC were 0.999 (95% CI 0.912-1.09) and 1.04 (95% CI 0.962-1.12), respectively. CONCLUSIONS: The experimental product regular human insulin and comparator Humulin® R are bioequivalent in patients with T1DM. Wider entry to the pharmaceutical market of affordable, biosimilar regular insulins may substantially improve access to insulin for many socioeconomically disadvantaged patients with diabetes.

The Review of Insulin Pens-Past, Present, and Look to the Future.

Currently, there are about 150-200 million diabetic patients treated with insulin globally. The year 2021 is special because the 100th anniversary of the insulin discovery is being celebrated. It is a good occasion to sum up the insulin pen technology invention and improvement which are nowadays the leading mode of an insulin delivery. Even though so many years have passed, insulin is still administered subcutaneously, that is why devices to deliver it are of great importance. Insulin pens have evolved only through the last decades (the reusable, durable pens, and the disposable, prefilled pens) and modern smart insulin pens have been developed in the last few years, and both types of the devices compared to traditional syringes and vials are more convenient, discrete in use, have better dosing accuracy, and improve adherence. In this review, we will focus on the history of insulin pens and their improvement over the previous decades.

A Multicenter, Prospective, Observational, Open-Label Study of the Safety and Comfort of Gensulin® Delivery Device Use in a Large Cohort of Adult and Elderly Patients with Type 2 Diabetes.

Insulin treatment is necessary for many patients with type 2 diabetes, and its delivery must be safe and comfortable. This study evaluated patients' safety and comfort when using a Gensulin® delivery device, GensuPen (Bioton), a reusable insulin pen device for injecting Gensulin® insulin among adult and elderly patients with type 2 diabetes. This was a 4-week multicenter, prospective, observational, open-label study in patients with diabetes mellitus type 2 who have recently started using a GensuPen. Overall, 10,309 patients (mean age: 63 ± 12.0 years; 47.9% female) were analyzed in this study. Of these, 2.5% had used an insulin delivery device before, and for 97.5%, GensuPen was the first delivery device they had used. Most (87.8%) of the patients rated the GensuPen as very good in setting the dose, 92.0% in confirmation of successful insulin administration, 80.9% in trigger location, and 75.0% in force needed for injection. The overall safety of the GensuPen use was high since severe hypoglycemia occurred only in 0.2% of the studied patients. There were 0.6% adverse events, none of which were serious. This real-life observation data shows that the GensuPen was well accepted and safe in this large patient population of adult and elderly patients with type 2 diabetes.

Improved insulin injection technique, treatment satisfaction and glycemic control: Results from a large cohort education study.

OBJECTIVE: The aim of this study was to elucidate injection techniques, treatment satisfaction and glycemic control after education among patients with type 2 diabetes. METHODS: 4513 insulin-treated diabetic patients enrolled in the observational study EGIDA II (Education and GensuPen In Diabetology II) filled out the questionnaire which focused on key insulin injection parameters, pain sensation scale and satisfaction of the treatment form before (visit 1) and after 3 months treatment with insulin injection (visit 2). The education was performed by trained healthcare professionals. To assess the utility and comfort during using new automatic injection system (GensuPen) we separated 2 groups: A - treated with GensuPen and B - treated with other pens. RESULTS: The education resulted in increased number of patients who properly remix cloudy insulin; inject insulin into skin; change every time the injection site; use the pen needle only once; prepare a pen for injection and store insulin. We noticed significant decrease in BMI and sensation of pain in both groups. Our study revealed that patients' satisfaction with the treatment increased with each of the 5 items (type of the treatment, mood, physical activity, vital energy, a sense of control over the disease) using a 5-point scale, with greater increase in group A. The utility and comfort (weight, thickness, easiness in remove pen cap, cleaning, twisting, keeping in hand the pen, dial the dose, readable signaling of injected dose) during using the GensuPen significantly increased in group A. Finally the mean glucose level in self-control diary was significantly lower after 3 months of the treatment in both groups, however the difference between visit 1 and 2 was greater in group A. CONCLUSION: The study showed that proper selection of pen and professional education can result in the improvement of insulin injection technique, higher patients' satisfaction and better glycemic control.

Diagnostic Accuracy of Glycated Haemoglobin and Average Glucose Values in Type 2 Diabetes Mellitus Treated with Premixed Insulin.

INTRODUCTION: Studies assessing the relationship between glycated haemoglobin (HbA1c) and average blood glucose (ABG) were conducted in small groups of patients on different treatments and may be biased for these reasons. The aim of the study was to assess the relationship between HbA1c and ABG in a large group of type 2 diabetes patients treated with premix insulin. METHODS: In 4257 patients treated with premixed insulin, the parallel point-of-care assessment of HbA1c and ABG from the preceding 90 days (ABG90), calculated automatically from all values measured by the glucometer, was performed twice. The regression formulas and respective values of HbA1c and ABG90 were calculated. RESULTS: The mean number of recorded glucose values/patient was 2.37 estimations per day. The regression formula calculated using data from the first assessment was HbA1c = 5.28 + 0.01487 × ABG90 and that using data from the second one was HbA1c = 4.78 + 0.01683 × ABG90. The slopes of the regression lines are lower than that in a similar analysis from the A1c-Derived Average Glucose (ADAG) study. The comparison of ADAG formula and the formula derived from the present study shows that both formulas give similar results at low HbA1c values, but differ at higher HbA1c values. Additionally, the 95% confidence interval is broader in the PROGENS study e.g. a 95% probability of certainty that the actual HbA1c value was greater than 7.0% (53 mmol/mol) was achieved only at an ABG90 value of 220 mg/dL. CONCLUSION: The relationship between HbA1c and ABG estimations may be different in various patients; therefore, it seems that the use of one equation in all populations may not be reliable. Broad assessment of ABG as a tool that may replace HbA1c measurements should be recommended only with caution, providing the possible limitations and confidence intervals. FUNDING: Bioton S.A.

Efficacy, Safety, and Quality of Treatment Satisfaction of Premixed Human and Analogue Insulin Regimens in a Large Cohort of Type 2 Diabetic Patients: PROGENS BENEFIT Observational Study.

Diabetes is a lifelong course disease, so insulin treatment has to be effective and safe, and patients should be satisfied with it. We aimed to compare efficacy, safety, and quality of treatment satisfaction of human and premixed analogue insulin among 3264 patients (53.58% women) with type 2 diabetes mellitus (T2DM) in a real-life environment. 2493 patients (62.77%) had been assigned to group I where before the inclusion into the study the treatment regimen has been changed from analogue to human premixed insulin and 771 patients (37.23%) to group II where the treatment with insulin analogue remained unchanged. At the end of the study, there was a reduction of HbA1c observed in both of the groups; however, Δ HbA1c was significantly higher in group 1 (-0.599 versus -0.406; P < 0.001 at visit 3 versus visit 1). The number of hypoglycemic episodes during the study observation was insignificantly reduced in both groups. Diabetes treatment satisfaction measured with DTSQ increased at the end of the study and was significantly better in group I compared to group II (P < 0.001). This observational study proved that both human and premixed analogue insulin are effective and safe, and patients are satisfied with the treatment.

PROGENS-HbA1c study: safety and effectiveness of premixed recombinant human insulin (Gensulin M30).

INTRODUCTION: Insulin analogues have gained widespread popularity. However, in many countries the use of these drugs is limited by their relatively high cost, so there is still a need for more cost-effective human insulin therapies. The aim of the study was to assess the effectiveness and safety of the premixed recombinant human insulin (rhuI) Gensulin M30 in a real-life setting. MATERIAL AND METHODS: The study group consisted of 4257 patients (2196 female, 2061 male) with type 2 diabetes, aged 63.7 ±9.4, with body mass index (BMI) 30.3 ±4.5 kg/m2 and diabetes duration 9 ±5.5 years. All patients were treated with premixed rhuI Gensulin M30. In 91.7% of patients, insulin was used in combination with metformin. In 3.7% of patients, it was used with sulphonylureas. The patients were observed for a period of 6 months. RESULTS: The total insulin dose on visit 1 was 36.1 ±18.7 U (0.42 ±0.22 U/kg), and by the end of the study it reached 40.3 ±18.9 U (0.48 ±0.22 U/kg). A significant, continuous decrease of the levels of glycated hemoglobin (HbA1c), along with fasting and postprandial plasma glucose, was observed during the study period. The frequency of hypoglycemia increased slightly during the study, although these figures remained low, especially with regard to severe hypoglycemic episodes (0.02 episodes/patient/year). The lowest number of hypoglycemic episodes occurred in patients treated with insulin and metformin, while the highest number of episodes was observed in patients treated with insulin alone. No weight changes were noted in the patients during the study. CONCLUSIONS: This study shows rhuI Gensulin M30 to be effective and safe in a real-life setting.

Diet-Related Knowledge and Physical Activity in a Large Cohort of Insulin-Treated Type 2 Diabetes Patients: PROGENS ARENA Study.

There is no doubt that behavioral intervention is crucial for type 2 diabetes mellitus (T2DM) prevention and management. We aimed to estimate dietary habits and diet-oriented knowledge as well as the level of physical activity in 2500 insulin-treated Polish type 2 diabetes mellitus (T2DM) patients (55.4% women). The mean age of the study participants was 64.9 ± 9.3 years, mean BMI was 31.4 kg/m2 ± 4.5, mean diabetes duration was 12.4 ± 6.9 years, and mean baseline HbA1c was 8.5% ± 1.2. At the study onset, all the patients completed a questionnaire concerning health-oriented behavior. Results showed a significant lack of diet-related knowledge. For example, only 37.5% recognized that buckwheat contains carbohydrates; the percentage of correct answers in questions about fruit drinks and pasta was 56.4% and 61.2%, respectively. As for the physical activity, only 57.4% of examined T2DM patients declared any form of deliberate physical activity. To conclude, the cohort of poorly controlled insulin-treated T2DM patients studied by us is characterized by insufficient diet-related knowledge and by a very low level of physical activity. Further studies on other populations of insulin-treated T2DM patients are required to confirm these findings.