Lege Artis Medicinae

[Biosimilar insulins on the horizon]


MARCH 20, 2015

Lege Artis Medicinae - 2015;25(03)

[Nowadays human insulins and insulin analogues are exclusively used in the clinical practice, when insulin therapy is needed. The patents of human insulins are expired and will expire soon for glargine, the first long-acting, basal insulin analogue preparation. The reliable production of biosimilar insulins is a new challenge for the pharmaceutical industry. Independently developed insulins with appreciable clinical efficacy have already become available in some countries where the quality criteria of regulatory process in place are less strict than in the European Union. The first approval for true biosimilar insulin, i.e. for biosimilar glargine was given in Europe in 2014. In this article, the characteristics of biosimilar insulins, especially the difficulties in the manufacturing process are reviewed in comparison with generic drugs. It is of note that potential efficacy and safety differences may occur due to even minor changes in the production, formulation and storage of the biological drugs. Therefore, biosimilarity should be investigated by detailed comparative pharmacokinetic and pharmacodynamic studies. Moreover, similar clinical efficacy and safety should be documented by randomized, comparative clinical trials. The potential impact of altered immunologic profile of biosimilar insulins should also be carefully monitored. ]



Further articles in this publication

Lege Artis Medicinae

[Getting Experiences without Drugs – An Interview with School Psychologist Edit Lippai dr. on Current Dependencies]

NAGY Zsuzsanna

Lege Artis Medicinae

[The Curative Tokaji ]

MAGYAR László András

Lege Artis Medicinae

[Protection of gastrointestinal system in cardiovascular diseases]


[Cardiovascular preventive drugs (nonsteroidal antiinflammatory drugs, aspirin, inhibitors of platelet aggregation, anticoagulants) are among the most frequently used medicines all over the world. Gastrointestinal (GI) complications (hemorrhage, ulceration, perphoration) are among the most frequent side effects of these drugs, however, differences in their pharmacodynamics properties and other pleiotropic effects may substantially modify these unwanted events. Authors, based on international and Hungarian guidelines, summarize the most important data for GI protection, focusing on the use of H-2 receptor blockers and proton pump inhibitors.]

Lege Artis Medicinae

[Physician and Science 3. – The Objective Physician or the Remedy Machine ]


Lege Artis Medicinae

[The role of hypoxia in tissue regeneration and in development of amplified aggressive fenotypes in malignant cancer]


[Several diseases are accompanied by hypoxic stress; elimination of it is an important physiological process. Our body provides a protective function which delays damage and destruction by hypoxia. In case of necrosis, it provides the mop up of the damaged area. This security system starts the regeneration in cells of the hypoxic zone which surrounds the necrotic area, resulting in the survival of the cells in hypoxic environment and ensuring the handling of the necrosis. The key molecules of the system are the hypoxia-induced factor molecules. The review discusses the physiological role of tissue hypoxia and normoxia and its effects on tissue regeneration. The physiological system triggered by the hypoxia-induced factor plays an important role in embryonic development, in wound healing and in numerous diseases (eg. myocardial infarction, stroke, vaculities, etc). Unfortunately, this system also plays a key role in several malignant tumors by rising the development of cells with increased aggressive fenotypes as well. The physiological process of regeneration starts in the hypoxic tumor cells aided by the hypoxia-induced factor system. The process results in neovascularization, and in the case of tissue damage, in the mop up of the necrotic tissue and in the restoration of tissue oxygenisation. However, after the formation of the new vascular network, tumor cells accustomed to hypoxia will not die but keep their original uncontrolled proliferation and anaerobic nature. Moreover the malignant nature of the cells will be increased by the genetic changes generated by the system of hypoxia- induced factors. The role of the hypoxia-induced factor system in tumor progression is discussed by the example of one of the most malignant tumors, malignant melanoma.]

All articles in the issue

Related contents

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.]


[Bone mineral density and diabetes mellitus - First results]


[INTRODUCTION - Data on bone mineral density (BMD) in diabetes mellitus are contradictory in the literature. Early studies described a decreased bone mineral density in type 1 diabetes mellitus (T1DM), but recent studies report no osteopenia in T1DM.The BMD may depend on the quality of treatment for diabetes mellitus and on the presence of chronic complications. In type 2 diabetes mellitus (T2DM) the BMD is not decreased, occasionally it can even be increased. PATIENTS AND METHODS - Bone mineral density was measured in 122 regularly controlled diabetic patients (T1DM: n=73, mean age: 43.6±11.1 years,T2DM: n=49, mean age: 61.8±9.8 years) by dual energy X-ray absorptiometry at the lumbar spine and at the femur. Results were compared to those of 40 metabolically healthy control persons with a mean age of 47.5±11.9 years.The patients’ carbohydrate metabolism was assessed by the average HbA1c level of the last three years.These values were 7.9±1.4 % in T1DM, and 7.5±1.7 % in T2DM. BMDs were classified based on the T-score and Z-score using the WHO criteria. RESULTS - There was no significant difference in T1DM or in T2DM compared to the reference group in the prevalence of either osteoporosis or of osteoporosis and osteopenia combined. CONCLUSION - BMD was not found to be decreased in patients with well-controlled metabolism compared to healthy controls.]

Hypertension and nephrology

[Summary of guidelines for American, European and International Companies in diabetes mellitus type 2 associated with hypertonia]

KÉKES Ede, DOLGOS Szilveszter

[The importance of hypertension in type 2 diabetes mellitus, the method of continuous blood pressure control and patient’s careas well as the forms of non-drug and drug therapy have been disclosed by presenting therapeutical recommendations from American, European scientific societies and international organizations. It has been established that the principles of care and treatment of hypertonia have basically remained unchanged in diabetes all over the world, despite the recent widespread debate over the interpretation of normal blood pressure and the consideration of the benefits of intensive or standard treatment.]

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

[Possibilities of applying basis/bolus method in treatment of adolescent with type 1 diabetes mellitus]


[INTRODUCTION - Since the end of the pastcentury, the basis/bolus method has been adeterminate factor of adjusting insulin thera-py. Experiences with insulin pump treatmentprove that well-quantified and adequatelytimed basal insulin treatment can fully com-pensate for the diurnal glucose-producingactivities of the liver and the diurnal changesin the activity of insulin receptors. Suitablyselected basal insulin treatment can, there-fore, keep the changes in blood sugar levelthat are dependent of the diet’s carbohydratecontent well under control. CASE REPORT - By presenting the approxi-mately five-year treatment of an adolescentboy, the author presents the current options(and failures) of insulin therapy that might beused with more or less success. Each treat-ment approach had its place in the variousstages of the patient’s diabetes. Nevertheless,insulin pump therapy, admittedly the moststate-of-the-art method today was unsuccess-ful due to patient’s lack of compliance, thusthis treatment had to be stopped. Still, on thebasis of the experiences with insulin pumptherapy, the restored intensive-conservativetreatment was set up on glargine basalinsulin, defining doses of bolus in correlationwith 10 grams of carbohydrate, which madethe diet less strict. This approach resulted ina considerable improvement of the patient’smetabolic profile. CONCLUSION - The right choice of thedoses and efficacy curve of basal insulin isessential for achieving a good metabolic bal-ance during intensive-conservative therapy.In case of deteriorating metabolic balance,suspending the inefficient insulin pump ther-apy is justified and means no disadvantagefor the patient, as long as the subsequentadjustment is prudent. By defining doses of ashort-acting bolus insulin analogue in corre-lation with carbohydrate intake along withglargine therapy permits adaptation to themetabolism of patients with poor compli-ance and unsatisfactory lifestyle - in expec-tation of better results. ]