• Medication treatment of diabetes mellitus type 2

    June 17, 2015

    Diabetes mellitus is a major risk factor for the development of cardiovascular and cerebrovascular morbidity and mortality. Despite the greater and more widespread “diabetes mellitus” problem awareness and the application of new therapeutic agents in Bulgaria, as in other European countries and the US, the metabolic control of diabetes in more than half the time is insufficient. Diabetes mellitus (DM) is a metabolic disease, characterized by hyperglycemia, resulting from insulin secretion disorder, insulin action, or both. The worldwide incidence of the disease is constantly increasing, and it is considered that patients with DM are about 382 million at present. This figure is expected to reach 522 million. In 2030 DM patients in Bulgaria will be about 500 000. Over 90% of the patients have DM type 2, which is the result of progressive defects in insulin secretion in the background of insulin resistance.

     

    Of the older antidiabetic agents metformin is best known. It is the first step in the treatment of DM. The question arises what would be the second step, as really early on, on average 2-3 years after the discovery of diabetes, a necessity arises to add to metformin as second treatment agent.

     

    Therapeutic targets in the treatment of DM type 2 include hyperglycemia and its acute symptoms control, as well as diabetes late complications prevention.

     

    Currently, the medication treatment of DM type 2 includes the use of several non-insulin oral and injectable agents groups: sulfonylureas, meglitinides, biguanides, thiazolidinediones, alpha-glucosidase inhibitors, DPP-4 inhibitors, GLP-1 agonists.

    Sulfonylureas – is a group of medicines that stimulate insulin secretion by binding to a specific receptor (SUR 1) on the surface of pancreas beta cells.

    Sulfonylureas reduce blood glucose on an empty stomach and postprandially. Glipizide, Gliglazid and Glimepiride are used in Bulgaria. Glimepiride is a representative of the sulfonylureas, believed to improve peripheral insulin sensitivity. Gliclazide, on the other hand, affects the rheological properties of blood and possibly protects vessels. Hypoglycemia and weight gain are the most common side effects of this group of drugs.

    Meglitinides are short acting prandial insulin secretagogues with a major effect the stimulation of the first phase insulin secretion. The main side effect is hypoglycaemia.

    Biguanides - the only representative currently being used is metformin. Metformin is an insulin sensitizer which acts at liver, skeletal muscle and adipose tissue level. It activates the AMP-dependent protein kinase (AMPK) – a key enzyme in the insulin signal transduction in cells and glucose and lipid metabolism. Metformin reduces hyperglycaemia, but does not affect the normal blood glucose levels. It has beneficial effects on the cardiovascular system and lipid metabolism, reduces plasma insulin levels, directly affecting endothelial dysfunction, fibrinolysis, oxidative stress, the processes of atherogenesis, the microcirculation of nonenzymatic glycation of proteins. It is neutral in terms of bodily weight. The most common side effects of its administration are gastro-intestinal complaints.

    Thiazolidinediones – the medicines in this group are agonists of the nuclear PPAR – γ receptor and modify the transcription of genes regulating glucose and lipid metabolism. Thiazolidinediones decrease the peripheral insulin resistance, stimulate adipogenesis and reduce visceral fat, having a beneficial effect on the endothelial dysfunction, fibrinolysis, blood pressure, and fatty liver. A representative of this group of medicines is Pioglitazone. The most frequent side effects are weight gain and retaining liquids.

    α-glucosidase inhibitors – specifically block alpha-glucosidases (enzymes necessary for the breakdown of poly, oligo and disaccharides to monosaccharides) on intestinal microvilli. The side effects of this group are mainly connected with the gastrointestinal tract.

    DPP-4 inhibitors – inhibit the enzyme DPP-4 and thereby prevent the degradation of incretins, which stimulate insulin secretion from pancreas beta cells. There is evidence of an increased incidence of pancreatitis when using DPP-4 inhibitors.

    GLP-1 receptor agonists – stimulate insulin secretion from pancreas beta cells, suppress glucagon secretion, slow gastric emptying and reduce appetite. The most common side effects are related to the digestive tract.

    In 2012, the American Diabetes Association and the European Association for the Study of Diabetes produced a Position Statement on the Control of Hyperglycemia in DM type 2, and in 2015 they published a second modern version. According to this Position, the first step in the treatment of DM type 2 is a change in lifestyle and metformin monotherapy. If in three months’ time the individual glycemic targets have not been reached, a switch is made to two medicines’ combination therapy, while upon failure in another three months – a third medicine is added to the therapy.

    To sum up:

    1. First line therapy – metformin
    2. Second line therapy – adding sulfonylureas to metformin
    3. Third-line therapy – replacement of sulfonylureas / metformin or adding pioglitazone, sitagliptin, vildagliptin at physician’s choice. Clinical trials’ data has shown that the addition of Pioglitazone reduces HbA1c to a greater degree than sitagliptin, vildagliptin (Chawla et al., 2013, Liu et al., 2013, Lee et al., 2013, Bolli et al., 2008, Kaur M. et al., 2014, Kaur K. et al., 2014)
    4. Fourth line therapy – Exenatide is added to metformin or sulfonylureas only when the BMI > 35,0 kg / m²

     

    Tchaikapharma High Quality Medicines AD offers these drugs, indicated for the treatment of DM type 2, on the Bulgarian market:

    Pioglitazone with the brand name Pisona:
    NHIF code: AF 505 – Pisona 15 mg x 30 tablets – with no additional payment for the patient
    NHIF code: AF 506 – Pisona 30 mg x 30 tablets – with no additional payment for the patient
    NHIF code: AF 507 – Pisona 45 mg x 30 tablets – with no additional payment for the patient

    Metformin with the brand name Metformin-Tchaikapharma  

    NHIF code: AF 341 – Metformin-Tchaikapharma   850 mg x 30 tablets – with no additional payment for the patient

    Glimepiride with the brand name Gliper

    NHIF code: AF 319 – Gliper 1 mg x 30 tablets – with no additional payment for the patient

    NHIF code: AF 321 – Gliper 2 mg x 30 tablets – with no additional payment for the patient

    NHIF code: AF 323 – Gliper 3 mg x 30 tablets – with no additional payment for the patient

    NHIF code: AF 325 – Gliper 4 mg x 30 tablets – with no additional payment for the patient
    Gliclazide with the brand name Diab

    NHIF code: AF 317 – Diab 80 mg x 60 tabletswith no additional payment for the patient

    Gliclazide with the brand name Diab МR

    NHIF code: AF 478 – Diab МR 30 mg tablets with modified release x 60 tablets – no additional payment for the patient