Lege Artis Medicinae



APRIL 21, 2006

Lege Artis Medicinae - 2006;16(04)

[Insulin detemir is a neutral, soluble, long-acting insulin analogue in which the amino acid threonineB30 has been removed and the LysB29 acylated with a 14-carbon fatty acid. The fatty acid modification allows insulin detemir to dihexamerisate and reversibly bind to human albumin upon administration. This brand new principle (self association and albumin binding) ensures slow absorption and a prolonged and consistent metabolic effect without a marked peak for up to 24 hours in patients both with type 1 and type 2 diabetes mellitus. Results of large clinical trials have shown that detemir can be efficiently used as basal insulin, supplemented with human regular insulin or aspart insulin taken before the main meals, in both type 1 and type 2 diabetes. Available data clearly demonstrate that the use of this insulin is associated with decreased variability of the fasting blood glucose values. In some of the studies the risk of (mostly nocturnal) hypoglycaemic episodes also dropped. It is important to note that patients using insulin detemir gained less or no weight compared to the group of patients treated with neutral protamine Hagedorn (NPH) insulin. Evaluation of long-term and wide-spread application of detemir needs further observations. Such trials are being conducted worldwide.]


  1. Diabétesz Gondozási Nemzeti Központ
  2. Semmelweis Egyetem, Általános Orvostudományi Kar, I. Sz. Belgyógyászati Klinika, Diabétesz Részleg
  3. Csepeli Egészségügyi Szolgálat, Diabetológia



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[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

[Optimalisation of basal insulin regimen for adolescent patients with type 1 diabetes]


[INTRODUCTION - During the total phase of type 1 (insulin-dependent) diabetes mellitus (T1DM), both the quantity and the quality of daily insulin doses must be determined to help the daily blood-glucose profile approach normoglycaemia, derived from the patient’s diet and regimen. Adolescence for young people with T1DM is a rather stressful - often shocking - psychosomatic state, due not only to the increased - but erratic - secretion of contrainsular hormones (predominantly growth hormone), but also to the special mental state of the child. Accordingly, choosing the right kind and amount of basal insulin to compensate the contrainsular effect is crucial for optimal treatment during this stage of life as well. CASE REPORT - We describe the process of optimising metabolic balance and basal insulin demand in a 11-year-old, adolescent girl with T1DM for 7.5 years using glargine insulin. In order to achieve this goal, both the dosage of glargine and the daily schedule of its administration needed to be modified. CONCLUSIONS - To achieve optimal metabolic results, both the quantity and the efficacy curve of basal insulin must and can be adapted to the actual stage of general somatic development. The demand for basal insulin during puberty may be well beyond the widely approved limit of 50%. Adapting the administration of glargine insulin to a daily schedule has the potential to counterbalance increasing contrainsular effects.]

Lege Artis Medicinae

[Insulin analogues and pregnancy]


[Near-normoglycaemic metabolic control in pregnant women with diabetes - started before conception in pregestational diabetes - decreases the frequency of maternal and foetal complications. Such control can be achieved by using optimalised systems of insulin therapy. A number of (ultra)rapid and long-acting insulin analogues became available during the last decade, which - on the basis of theoretical considerations - might be used to maintain normoglycaemia. Summarising the data available today, the use of rapid insulin analogues (lispro, aspart) seem to be effective and safe during pregnancy. Some questions arise, however, about their modes of application. The use of long-acting insulin analogues in pregnancy is currently not indicated. Further trials are needed to prove their efficacy and safety in diabetic pregnancy.]

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

[Cost minimization analysis of basal insulin analogues in the treatment of type 2 diabetes]

MERÉSZ Gergő, TABÁK Gy. Ádám, KALÓ Zoltán

[INTRODUCTION - Basal insulin analogues are essential drugs for the treatment of type 2 diabetes mellitus. Basal insulin analogues have been shown to reduce the frequency of hypoglycaemia versus NPH insulin, and thus may be beneficial in the treatment of type 2 diabetes. Here we present a cost-minimisation analysis of basal insulin analogues, comparing insulin glargine and insulin detemir available in Hungary. METHODS - A literature review was conducted to identify randomized, controlled clinical trials with a duration of 12 weeks or more in which a direct comparison of insulin glargine and insulin detemir was made in patients with type 2 diabetes. In a meta-analysis of the eligible trials, the following endpoints were investigated: metabolic status, body weight, frequency of hypoglycaemia, insulin doses administered and the number of insulin injections required. If a high heterogeneity (I2>75%) was found, meta-regression was performed to identify the underlying reasons. The funder’s perspective was applied in the cost-minimization analysis by taking into account the cost of the drug and of medical devices necessary for its administration, based on the daily number of insulin injections. RESULTS - No further studies were found in addition to those included in a metaanalysis published by The Cochrane Library. On the basis of three eligible studies, insulin detemir was injected more frequently compared with glargine (weighted mean difference: 0.42 95% CI 0.14-0.69 injections/day). High heterogeneity was present in case of two endpoints: the incidence of overall hypoglycaemia per patient-year (I2=83%), and daily basal insulin dose in units per body weight (I2=94%). The reason for the high heterogeneity in hypoglycaemia rates was not identified by meta-regression; however, the difference in insulin doses per body weight was negatively associated with body weight (-0.027 IU/kg per 1 kg, 95%CI: -0.051; -0.004). On the basis of the present meta-analysis and meta-regression, our calculations suggest that treating an average weight (90 kg) patient with type 2 diabetes with insulin glargine would result in an annual cost reduction of 93 452 HUF compared with insulin detemir by employing gross public drug prices. CONCLUSION - On the basis of the available clinical evidence, insulin glargine might be a cost-saving alternative of insulin detemir in an average-weight patient with type 2 diabetes. In an era of scarce resources, the role of therapeutic alternatives offering cost savings with the same efficacy become more important. The generalisability of our conclusions might be influenced by potential differences in the manufacturers’ claw-back rate of detemir vs glargine insulin.]