Lege Artis Medicinae

[A new option in insulin therapy that decreases the risk of hypoglycaemia]

BECHER Péter, MÁJER Katalin, PATAI Árpád

APRIL 20, 2013

Lege Artis Medicinae - 2013;23(03-04)

[Insulin degludec is a novel, ultra-long acting basal insulin analogue with a safety and efficacy similar to those of insulin glargine. Its main advantage is its ability to significantly reduce hypoglycaemia, particularly nocturnal hypoglycaemia. We present in detail the results of the BEGIN clinical studies with degludec.]



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Lege Artis Medicinae



[Insulin aspart (B28 Asp-insulin), which is produced by recombinant DNA technology, is a fast-acting insulin analogue. Due to the aspartate for proline substitution at position 28 of the Bchain, the insulin molecule's tendency for selfassociation is diminished, therefore, insulin aspart rapidly dissociates into dimeric and monomeric forms and absorbs quickly and easily after subcutaneous administration. Compared to human regular insulin, insulin aspart has a faster onset of activity, a higher plasma peak and a shorter duration of action. Overall, the pharmacokinetic profile of insulin aspart better mimics the physiological postprandial insulin secretion. Therefore, insulin aspart can be used for prandial insulin substitution in order to decrease postprandial blood glucose excursion. It should be administered immediately before meals, but some observations suggest that it can also be used after finishing meal. This allows a more flexible lifestyle for patients. Insulin aspart can be used in both type 1 and type 2 diabetes. Compared to regular human insulin, a moderate decrease in the HbA1c values and fewer nocturnal hypoglycaemic events are expected from insulin aspart use. Insulin aspart is appropriate for pump treatment as well. It has recently been approved for use in pregnancy, whereas for children and adolescents the expected benefits should be weighed against the more modest clinical experience available. Similarly to other insulin analogues, results of long-term clinical investigations with insulin aspart with regard to the development of complications are not yet available.]

Lege Artis Medicinae

[Switching from human basal insulin to once daily insulin detemir in type 2 diabetic patients treated by basal-bolus regimen - Results from the LEONCET2, an observational, prospective, multicenter study]


[Insulin analogues have been developed in order to overcome some drawbacks of human insulins. Switching from a human insulin-based basal- bolus regimen to once daily detemir could result in improved metabolism and increased safety of the therapy. We assessed the effects of switching from human NPH-insulin to once daily detemir insulin in patients with type 2 diabetes mellitus treated with a basal-bolus insulin regimen. We evaluated the data of 1,474 patients with diabetes (age: 59.1±9.8 years, body weight 89.6±8.6 kg, BMI 31.6±5.4 kg/m2) in an observational, prospective, 24-week, multicenter study. All patients were treated with a basal-bolus regimen consisting of human NPH as basal insulin and a human or analogue insulin as bolus insulin. After enrollment, patients received once daily detemir insulin instead of NPH-insulin, while treatment with bolus insulin was continued. Patients were examined at weeks 12 and 24. By week 24, the mean HbA1c value, irrespective of BMI-categories, decreased significantly (p<0.0001) from 8.63±1.01% by 0.79±0.63%. Fasting blood glucose level decreased from 8.86±1.78 mmol/l to 7.09±1.31 mmol/l; p<0.0001). The target level of HbA1c (<7.0%) was reached by 194 patients (13.1%). The patients’ body weight decreased significantly by week 12 (-0.69±2.00 kg; p<0.0001) and by week 24 (-1.28±2.80 kg; p<0.0001). The changes were more pronounced in higher than in lower BMI-categories (p for trend <0.0001). The mean daily doses of basal insulin were increased from 0.28 IU/kg to 0.33 IU/kg while those of bolus insulins were not changed. The rate of severe hypoglycaemic events decreased significantly (p=0.048) from 2.95 [daytime 1.02, nocturnal 1.93] to 0.06 [daytime 0.04, nocturnal 0.02] episodes/patient-year. In patients with type 2 diabetes mellitus treated with basal-bolus regimen, switching from human basal insulin to once daily insulin detemir results in a significantly improved metabolism, as well as fewer hypoglycaemic events and decreased body weight. Nevertheless, the low rate of patients reaching the glycaemic target implicates that some factors other than an appropriate basal insulin substitution have a role in achieving an optimal metabolic control.]

Lege Artis Medicinae

[Efficiency and safety of biphasic aspart insulin therapy in clinical studies]

GERŐ László

[Six-to-eight years after the diagnosis of type 2 diabetes the majority of patients require insulin treatment. Premixed insulin therapy provides an insulin profile that is closer to the physiological profile than that achieved by basal insulin supplementation and, in some cases, may serve as an alternative treatment in patients for whom intensified insulin therapy is unsuitable. However, if premixed human insulins are used, nocturnal hypoglycaemia occurs relatively frequently. Furthermore, patients must keep a lag-time of 30-45 minutes between the injection of insulin and eating. In contrast, if premixed insulin analogues are used, there is no need for such lag-time and both nocturnal and severe hypoglycaemia are less frequent than with human premixed therapy. The superiority of premixed insulin analogues compared with premixed human insulin therapy has been confirmed by a number of prospective, randomised controlled trials and retrospective analyses. The author summarises the results of these studies, emphasising the beneficial effects of premixed insulin analogues in the therapy of type 2 diabetes.]

Lege Artis Medicinae

[Insulin dose titration in type 1 diabetes mellitus: A blessing or a curse?]


[INTRODUCTION - Knowing the pharmacokinetic properties of different insulins, useful treatment algorithms can be set up for the majority of our insulin-treated patients. When planning either a human or an analogue basal-bolus regimen, the first task is to determine the daily insulin requirement, followed by determination of the optimal rate of basal and bolus insulins. CASE REPORT - In a 33-year old, moderately obese man with type 1 diabetes who received 180 U daily insulin doses, accumulated hypoglycaemic episodes with neuroglycopenic symptoms occured. After cessation of the original insulin therapy and starting an analogue basal-bolus treatment regimen, both the carbohydrate metabolism and the overall quality of life of the patient have significantly improved. Optimal metabolic control was achieved by a basal insulin ratio above 50%. CONCLUSION - Using elements of the analogue basal-bolus regimen - one of the state-of-the-art forms of insulin treatment - at the appropriate dose and dose ratio, it is possible to comply with the therapeutic requirements of our age. However, if this weapon is used inappropriately, it might actually harm patients.]

LAM Extra for General Practicioners



[INTRODUCTION - Observational studies have verified that even in routine diabetes care, up to 1.3% reduction in HbA1c can be achieved with the initiation of a long-acting basal insulin analogue. We can get the same results in our patients using an insulin titration algorithm and close diabetological control. CASE REPORT - Metformin therapy of a 68-year old, moderately obese woman with type 2 diabetes was complemented by a long-acting basal insulin analogue (insulin glargine). Before initiation of insulin therapy, the patient received thorough dietetic and diabetic education by a qualified dietician and a diabetes nurse. The starting dose of insulin was 10 U, and then the patient was asked to increase the dose by 2 U every 3rd day depending on the mean of self-monitored fasting plasma glucose values in the previous 2 days. With the aid of a titration algorithm, optimal carbohydrate metabolism has been verified by laboratory parameters assessed 3 months later. CONCLUSION - Insulin self-titration based on appropriate patient education and close professional control makes a relatively simple therapeutic system the optimal decision in terms of a rapid and chronic normalisation of glucose control in a large patient group.]