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Hypertension and nephrology

OCTOBER 23, 2019

[GLP-1 receptor agonists in the treatment of type 2 diabetes]

WINKLER Gábor

[The glucagon-like peptide (GLP)-1 receptor agonists and somewhat later, the sodium-glucose cotransporter (SGLT) -2 inhibitors have brought new perspectives in the antihyperglycemic treatment of type 2 diabetes. The article overviews clinicopharmacologic characteristics of the GLP-1 receptor agonist group, their glycemic and non-glycemic effects, results of the cardiovascular endpoint studies as well as their place in the recent therapeutic guidelines. It is proven, that both glycemic and weight reducing effect is greater of the long-acting (non-prandial) coumpounds as compared to that of the short acting (prandial) derivates, further, that in studies with cardiovascular endpoints they reduced the relative risk of the composite endpoint of non-fatal myocardial infarct, non-fatal stroke and cardiovascular death. Due to the favolurable glycemic and non-glycemic properties their use is advised already in the early course of type 2 diabetes, as combination of the metformin therapy.]

Lege Artis Medicinae

DECEMBER 21, 2011

[The newest DPP-4-inhibitor: linagliptin]

KIS János Tibor

[Linagliptin is a xantin-based, highly selective, potent inhibitor of dipeptidyl peptidase- IV (DPP-4). By inhibiting DPP-4, linagliptin reduces the degradation of endogenous incretin hormones, and thus increases insulin secretion and decreases glucagon secretion in the pancreatic islets in a glucose-dependent manner. The author summarises the most important clinical trials with linagliptin, which highlight those features of linagliptin that distinguish it from other DPP-4 inhibitors.]

Lege Artis Medicinae

MARCH 20, 2010

[A new era in the treatment of patients with type 2 diabetes - Significance of the incretin analogue liraglutide from an internist’s perspective]

FARSANG Csaba

[Therapy of patients with type-2 diabetes has two important features: in addition to the nonpharmacological approach (changes in lifestyle and diet, smoking cessation, physical exercise), pharmacological intervention is needed to reach the target level of blood sugar, and those of other cardiometabolic risk factors (blood pressure, body weight, lipids, uric acid). Unfortunately, it is a worldwide problem that only a small fraction of diabetic patients reach all these goals. This is why it is very important to have drugs which can not only decrease the blood sugar level, but have beneficial effect on several cardiometabolic factors. Antidiabetic drugs affecting incretin system, the GLP-1 analogues or -mimetics, and DPP-4 inhibitors open a new era in the treatment of diabetic patients, because in addition to the reduction of blood glucose level, they may have beneficial effects on blood pressure, blood lipids and body weight. Among these drugs the newly registered liraglutide has an important role, because it stimulates secretion of insulin in a glucose-independent manner, and it also reduces the secretion of glucagon which is a well known endogenous substance that increases blood glucose level. It is important to note that liraglutide decreases appetite, body weight and blood pressure of diabetic patients. Several clinical pharmacological studies has been completed with liraglutide. Of these the LEAD (Liraglutide Effect and Action in Diabetes) program is of outstanding value because it proved that either in monotherapy or in combination with other antidiabetics it effectively decreased blood sugar level, body weight, and had a beneficial effect on systolic blood pressure.]

Lege Artis Medicinae

SEPTEMBER 20, 2010

[Efficacy and safety of sitagliptin during long term treatment in patients with type 2 diabetes]

HIDVÉGI Tibor

[Due to the progressive nature of the type 2 diabetes mellitus and treatment requires prolonged lifestyle and/or pharmacologic management, the long term efficacy, durability and safety of newer antihyperglycemic agents are important considerations. Metformin is the most common prescribed oral antihyperglycemic agent (OHA) for initial therapy. Often, initial single oral agent is not sufficient to maintain good glucose control, combination of OHA are usually required to manage patients with type 2 diabetes. Incretinbased therapies (e.g. dipeptidyl peptidase 4 (DPP 4) inhibitors and analogues of glucagon like peptide 1) are newer compounds available for the treatment of type 2 diabetes. Sitagliptin is a once-daily OHA with a novel mechanism of action that targets the incretin axis. Addition of sitagliptin to ongoing metformin therapy was well tolerated and resulted in significant glycemic improvement after 30-104 weeks of treatment in patients with type 2 diabetes.]

Lege Artis Medicinae

OCTOBER 20, 2010

[A new DPP-IV inhibitor: saxagliptin]

KIS János Tibor, MÉSZÁROS Gabriella

[Saxagliptin is a selective, potent inhibitor of dipeptidyl peptidase-IV (DPP-IV). By inhibiting DPP-IV, saxagliptin reduces the degradation of endogenous incretin hormones, resulting in increased glucose-dependent insulin and decreased glucagon secretion from the pancreas islets. Clinical trials of saxagliptin as monotherapy and as combination therapy with other oral antidiabetic medications including metformin, glibenclamide, glipizide, pioglitazone and rosiglitazone have demonstrated clinical benefits in different glycaemic endpoints. Due to its glucose- dependent mechanism of action, saxagliptin as monotherapy or in combination with metformin results in a very low risk for hypoglycemia. It has also been shown to be generally well-tolerated, with not having any relevant effect on weight. The authors summarize the most important saxagliptin trials.]

Lege Artis Medicinae

NOVEMBER 10, 2008

[DISEASES OF THE EXOCRINE PANCREAS AND DIABETES MELLITUS]

CZAKÓ László

[Exocrine and endocrine pancreas constitutes close anatomical and functional links accordingly, any disease affecting one of these sectors will inevitably affect the other. Acute and chronic pancreatitis, pancreatic surgery, cystic fibrosis and pancreatic cancer are those pancreatic conditions that might cause diabetes mellitus. The development of diabetes greatly influences the prognosis and quality of life of patients with exocrine pancreatic diseases. The lack of glucagon and the impaired absorption of nutrients may cause life-threatening complications, such as hypoglycaemia, and the micro- and macrovascular complications may impair the organ functions. Diabetes mellitus is an independent risk factor of mortality in those with exocrine pancreatic diseases. Pancreatic diabetes is a distinct metabolic and clinical form of diabetes, requires special treatment. Diet and pancreatic enzyme replacement therapy may be sufficient in the early stages. Oral antidiabetic drugs are not recommended. If the diet proves inadequate to reach the glycaemic goals, regular insulin treatment is demanded. There are special impairments of the exocrine function and the pancreatic morphology at diabetic patients that resemble to chronic pancreatitis. Atrophy of the exocrine tissue may caused by the lack of trophic insulin. Hyperglycaemia can activate the stellate cells that lead to pancreatic fibrosis. The microangiopathy and neuropathy, as well as the lack of islet hormone action - responsible for the exocrine pancreas regulation - will cause further damage on the pancreas glandular tissue. In the event of a proven impairment of the pancreatic exocrine function in diabetes mellitus, pancreatic enzyme replacement therapy is recommended. This may improve the nutritional condition and decrease the metabolic instability.]

Lege Artis Medicinae

NOVEMBER 10, 2008

[INCRETIN MIMETICS AND INCRETIN ENHANCERS: NEW THERAPEUTIC TOOLS IN THE TREATMENT OF PATIENTS WITH TYPE 2 DIABETES MELLITUS]

JERMENDY György

[Incretins are hormone-like peptides secreted by specific cells of the small intestine mucosa. Their two main representatives are the glucagon-likepeptide- 1 (GLP-1 and the glucose-dependent insulinotropic peptide, (GIP) the release of which is stimulated by meals. The main action of incretins is to enhance insulin secretion following meals. They are rapidly metabolized in the circulation by the enzyme dipeptidyl peptidase IV (DPP-IV). Patients with type 2 diabetes have markedly impaired incretin-mediated insulin secretion mainly due to decreased secretion of GLP-1. Research in the last years has opened up a new therapeutic option to treat patients with type 2 diabetes. Continuous intravenous use of GLP-1 cannot be widely used in clinical practice; however, GLP-1-mimetics that have an agonist effect on the receptors but are resistant to degradation by DPP-IV have been developed. The GLP-1 agonist xenatide, due to its incretin mimetic property, stimulates postprandial insulin secretion, suppresses glucagon secretion, delays gastric emptying and increases sense of fullness thus resulting in weight reduction. In experimental settings, exenatide has a documented beta-cell protecting property. Its disadvantages include the fact that it can only be administered subcutaneously and that it has a well characterized side effect profile. On the contrary, the DPP-IV inhibiting incretin enhancers (sitagliptin, vildagliptin) can be used orally and are well tolerated. Exenatide, sitagliptin and vildagliptin are the first representatives of incretin mimetics and incretin enhancers. Sitagliptin has been available in Hungary since August, 2008. Their effect to reduce blood glucose and HbA1c should mainly be exploited in combination therapy, preferably with metformin. The availability of incretin mimetics and incretin enhancers will offer new therapeutic options for treating patients with type 2 diabetes. Nevertheless, the final assessment of these new drugs will require long-term experience in the clinical practice.]

Clinical Neuroscience

OCTOBER 20, 2003

[Hypothalamic regulation of the food intake]

PALKOVITS Miklós

[The central regulation of the food intake is organized by a long-loop mechanism involving humoral signals and afferent neuronal pathways to the hypothalamus, obligatory processing in hypothalamic neuronal circuits, and descending commands through vagal and spinal neurons to the body. Receptors sensitive to glucose metabolism, body fat reserves, distension of the stomach, as well as neuropeptide and cannabinoid receptors have been identified and localized in the hypothalamus. Five groups of cells in the hypothalamus - arcuate, paraventricular, ventromedial and dorsomedial nuclei, and the dorsolateral hypothalamic area - contain neurons with either anorexic actions (α-MSH, CART peptide, corticotropin-releasing hormone, urocortin III, cholecystokinin, glucagon-like peptides) or that stimulate food intake (neuropeptide Y, agouti-related peptide, orexins, melanin concentrating hormone, galanin). Intrahypothalamic neuronal circuits exist between these peptidergic neurons including the arcuate-paraventricular and arcuate-dorsolateral hypothalamic projections. Circulating substances carrying signals connected to changes in body food homeostasis and energy balance (leptin, ghrelin, insulin, glucose) enter the hypothalamus mainly through the arcuate nucleus. Neurons in the medulla oblongata that express leptin and insulin receptors, as well as neuropeptide mediators project to the hypothalamus. Vica versa, hypothalamic neurons give rise to projections to autonomic centers in the brainstem and the spinal cord with potential for stimulation or inhibition of food intake, energy balance and ingestion behavior.]