BACKGROUND: The effectiveness of glucose-lowering drugs (GLDs) is unknown among patients with dementia. OBJECTIVE: To analyze all-cause mortality among users of six GLDs in dementia and dementia-free subjects, respectively. METHODS: This was a longitudinal open-cohort registry-based study using data from the Swedish Dementia Registry, Total Population Register, and four supplemental registers providing data on dementia status, drug usage, confounders, and mortality. The cohort comprised 132,402 subjects with diabetes at baseline, of which 11,401 (8.6%) had dementia and 121,001 (91.4%) were dementia-free. Subsequently, comparable dementia - dementia-free pairs were sampled. Then, as-treated and intention-to-treat exposures to metformin, insulin, sulfonylurea, dipeptidyl-peptidase-4 inhibitors, glucagon-like peptide-1 analogues (GLP-1a), and sodium-glucose cotransporter-2 inhibitors (SGLT-2i) were analyzed in the parallel dementia and dementia-free cohorts. Confounding was addressed using inverse-probability weighting and propensity-score matching, and flexible parametric survival models were used to produce hazard ratios (HR) and 95% confidence intervals (CI) of the association between GLDs and all-cause mortality. RESULTS: In the as-treated models, increased mortality was observed among insulin users with dementia (HR 1.34 [95%CI 1.24-1.45]) as well as in dementia-free subjects (1.54 [1.10-1.55]). Conversely, sulfonylurea was associated with higher mortality only in dementia subjects (1.19 [1.01-1.42]). GLP-1a (0.44 [0.25-0.78]) and SGLT-2i users with dementia (0.43 [0.23-0.80]) experienced lower mortality compared to non-users. CONCLUSION: Insulin and sulfonylurea carried higher mortality risk among dementia patients, while GLP-1a and SGLT-2i were associated with lower risk. GLD-associated mortality varied between dementia and comparable dementia-free subjects. Further studies are needed to optimize GLD use in dementia patients.

• Klíčová slova
• Antidiabetics, dementia, diabetes, hyperglycemia, mortality, propensity-score,
• MeSH
• demence * komplikace   MeSH
• diabetes mellitus 2. typu * komplikace   farmakoterapie   epidemiologie   MeSH
• glifloziny * terapeutické užití   MeSH
• glukagonu podobný peptid 1 MeSH
• glukosa MeSH
• hypoglykemika terapeutické užití   MeSH
• inzulin terapeutické užití   MeSH
• lidé MeSH
• sulfonylmočovinové sloučeniny terapeutické užití   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• glifloziny * MeSH
• glukagonu podobný peptid 1 MeSH
• glukosa MeSH
• hypoglykemika MeSH
• inzulin MeSH
• sulfonylmočovinové sloučeniny MeSH

BACKGROUND: The effect of antidiabetic medication on cognitive function is unclear. We analyzed the association between five antidiabetic drugs and change in Mini-Mental State Examination (MMSE) scores in patients with diabetes and dementia. METHODS: Using the Swedish Dementia Registry and four supplementary Swedish registers/databases, we identified 1873 patients (4732 observations) with diagnosis of type 2 diabetes (diabetes) and Alzheimer's disease or mixed-pathology dementia who were followed up at least once after dementia diagnosis. Use of metformin, insulin, sulfonylurea, thiazolidinediones (TZD), and dipeptidyl-peptidase-4 inhibitors (DPP-4i) was identified at baseline. Prevalent-user, incident-user, and drug-drug cohorts were sampled, and propensity-score matching was used to analyze comparable subjects. Beta coefficients with 95% confidence intervals (CI) from the random intercept and slope linear mixed-effects models determined the association between the use of antidiabetic medications and decline in MMSE score points between the follow-ups. Inverse-probability weighting was used to account for patient dropout. RESULTS: Compared to non-users, prevalent users of metformin (beta 0.89, 95% CI 0.44; 1.33) and DPP-4i (0.72, 0.06; 1.37) experienced a slower cognitive decline with time. Secondly, compared to DPP-4i, the use of insulin (-1.00, -1.95; -0.04) and sulfonylureas (-1.19; -2.33; -0.04) was associated with larger point-wise decrements in MMSE with annual intervals. CONCLUSIONS: In this large cohort of patients with diabetes and dementia, the use of metformin and DPP-4i was associated with a slower decline in MMSE scores. Further examination of the cognitive effects of metformin and incretin-based medications is warranted.

• Klíčová slova
• Antidiabetics, DPP-4i, Dementia, Diabetes, MMSE, Metformin,
• MeSH
• demence * komplikace   farmakoterapie   epidemiologie   MeSH
• diabetes mellitus 2. typu * komplikace   farmakoterapie   epidemiologie   MeSH
• hypoglykemika terapeutické užití   MeSH
• inhibitory dipeptidylpeptidasy 4 * terapeutické užití   MeSH
• lidé MeSH
• sulfonylmočovinové sloučeniny terapeutické užití   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• hypoglykemika MeSH
• inhibitory dipeptidylpeptidasy 4 * MeSH
• sulfonylmočovinové sloučeniny MeSH

Type 2 diabetes mellitus is a heterogeneous medical condition involving multiple pathophysiological mechanisms. Its successful treatment requires an individualized approach and frequently combined therapy with utilizing its effect on multiple levels. Current possibilities enable the employment of such procedures to an incomparably greater extent than before. The effects of different classes of oral antidiabetic drugs on the reduction of glycemia and HbA1c is mutually comparable. However differences are observed in the proportions of patients who met the required criteria, regarding the increase in weight, incidence of hypoglycemia as well as the effect on cardiovascular, renal or oncologic morbidity and mortality, and severity of specific adverse effects, potential risks and contraindications. The presented text provides the reader with the information about the Consensual therapeutic algorithm for the treatment of type 2 diabetes mellitus in compliance with SPC, the ADA/EASD amended indicative limitations and recommendations, formulated by the Committee of the Slovak Diabetes Society.Key words: biguanides - gliflozins - gliptins - glitazones - GLP-1-receptor agonists - insulin - sulfonylurea.

• MeSH
• diabetes mellitus 2. typu * farmakoterapie   MeSH
• glykovaný hemoglobin MeSH
• hypoglykemika * terapeutické užití   MeSH
• inhibitory dipeptidylpeptidasy 4 * terapeutické užití   MeSH
• inzulin terapeutické užití   MeSH
• krevní glukóza MeSH
• lidé MeSH
• sulfonylmočovinové sloučeniny terapeutické užití   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• směrnice pro lékařskou praxi MeSH
• Geografické názvy
• Slovenská republika MeSH
• Názvy látek
• glykovaný hemoglobin MeSH
• hypoglykemika * MeSH
• inhibitory dipeptidylpeptidasy 4 * MeSH
• inzulin MeSH
• krevní glukóza MeSH
• sulfonylmočovinové sloučeniny MeSH

PURPOSE OF REVIEW: There are currently over 40 different drugs in 12 distinct classes approved in the USA to treat patients with type 2 diabetes mellitus. This review summarizes our current knowledge about potential side effects of antidiabetic therapy and attempts to apply it to a clinical practice setting. RECENT FINDINGS: Given the heterogeneity of both the patients and the disease, it is mathematically impossible to test every available drug combination in long-term outcome, prospective, randomized blinded fashion before a clinician decides which agent(s) to prescribe to a specific patient in a given situation. To complicate the clinician's dilemma, there is lack of available tests to predict an individual's response or propensity to side effects. Further, the data available are derived from small, short-term registration trials and typically focus on relative rather than absolute risks of any given drug and do not address the potential adverse outcomes if a patient's diabetes remains untreated. Clinicians have to personalize their choice of antidiabetic therapy based both on the specific characteristics of the patient in front of them (stage of diabetes and its complications, overall health status, socioeconomic situation, other medications present, desire to improve control of diabetes, etc.) and the current knowledge about the relative and absolute balance of benefits and risks of any individual medication in that specific patient. It has to be recognized that this requires constant re-evaluation as database of our experience with antidiabetic therapy expands.

• Klíčová slova
• Antidiabetic medications, Drug side effects, Treatment of type 2 diabetes, Type 2 diabetes mellitus,
• MeSH
• agonisté receptoru pro glukagonu podobný peptid 1 MeSH
• biguanidy škodlivé účinky   terapeutické užití   MeSH
• diabetes mellitus 2. typu farmakoterapie   MeSH
• hypoglykemika škodlivé účinky   terapeutické užití   MeSH
• lidé MeSH
• prospektivní studie MeSH
• sulfonylmočovinové sloučeniny škodlivé účinky   terapeutické užití   MeSH
• thiazolidindiony škodlivé účinky   terapeutické užití   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• agonisté receptoru pro glukagonu podobný peptid 1 MeSH
• biguanidy MeSH
• hypoglykemika MeSH
• sulfonylmočovinové sloučeniny MeSH
• thiazolidindiony MeSH

HNF4A mutations cause increased birth weight, transient neonatal hypoglycemia, and maturity onset diabetes of the young (MODY). The most frequently reported HNF4A mutation is p.R114W (previously p.R127W), but functional studies have shown inconsistent results; there is a lack of cosegregation in some pedigrees and an unexpectedly high frequency in public variant databases. We confirm that p.R114W is a pathogenic mutation with an odds ratio of 30.4 (95% CI 9.79-125, P = 2 × 10(-21)) for diabetes in our MODY cohort compared with control subjects. p.R114W heterozygotes did not have the increased birth weight of patients with other HNF4A mutations (3,476 g vs. 4,147 g, P = 0.0004), and fewer patients responded to sulfonylurea treatment (48% vs. 73%, P = 0.038). p.R114W has reduced penetrance; only 54% of heterozygotes developed diabetes by age 30 years compared with 71% for other HNF4A mutations. We redefine p.R114W as a pathogenic mutation that causes a distinct clinical subtype of HNF4A MODY with reduced penetrance, reduced sensitivity to sulfonylurea treatment, and no effect on birth weight. This has implications for diabetes treatment, management of pregnancy, and predictive testing of at-risk relatives. The increasing availability of large-scale sequence data is likely to reveal similar examples of rare, low-penetrance MODY mutations.

• MeSH
• diabetes mellitus 2. typu farmakoterapie   genetika   MeSH
• dospělí MeSH
• genetická predispozice k nemoci genetika   MeSH
• haplotypy genetika   MeSH
• hepatocytární jaderný faktor 4 genetika   MeSH
• hypoglykemika terapeutické užití   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mutace genetika   MeSH
• odds ratio MeSH
• porodní hmotnost genetika   fyziologie   MeSH
• senioři MeSH
• sulfonylmočovinové sloučeniny terapeutické užití   MeSH
• výpočetní biologie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• hepatocytární jaderný faktor 4 MeSH
• hypoglykemika MeSH
• sulfonylmočovinové sloučeniny MeSH

INTRODUCTION: In the Czech Republic, patients with diabetes mellitus (DM) are followed and treated predominantly by specialists (approx. 80% at a specialist diabetology clinic), a minor part by general practitioners (up to 20%). Long-term development of the changes in prescribing metformin and sulfonylurea in the Czech Republic and its concordance with recommended procedures has not been evaluated until now. GOAL: Comparison of the development of metformin (MET) and sulfonylurea (SU) prescriptions in the period of 2002-2006 with that of 2010-2014 in a representative sample of the patient population with DM kept in the database of the General Health Insurance Company of the Czech Republic (VZP) which provided health care coverage for 63% of Czech Republic population in 2014. METHODOLOGY: We identified all individuals in the VZP database who had a record of DM diagnosis (E10-E16 based on ICD 10) or who had any antidiabetic therapy prescribed (ATC group A10) in the periods of 2002-2006 and 2010-2014. A cohort of patients was extracted for analysis, who had an agent from A10 group prescribed at least once in a relevant year (n=308,962 in 2002; n=426,695 in 2014). A number of patients was evaluated for each year, who had at least once MET or SU prescribed. The number of patients treated with MET or SU was then expressed as a percentage of all who had any therapy from A10 group prescribed in the year in question. RESULTS: Metformin prescriptions have linearly risen from 43% to 77%, while sulfonylurea prescriptions have linearly decreased from 65% to 37%. CONCLUSION: The analysis presents the first evaluation of the development of metformin prescriptions conducted in the Czech Republic and evaluation of its concordance with the recommended procedures for the treatment of DM. The amount of metformin prescribed in the Czech Republic increased from 43% to 77% while the amount of SU prescribed decreased from 65% to 37% between 2002 and 2014. This development and the current ratio between the prescribed amounts of MET and SU demonstrate the implementation of the recommended procedures into practice and prove the high quality of care for patients with DM2T in specialists--diabetologists surgeries.

• MeSH
• časové faktory MeSH
• diabetes mellitus 2. typu farmakoterapie   MeSH
• dospělí MeSH
• hypoglykemika terapeutické užití   MeSH
• lékové předpisy statistika a číselné údaje   MeSH
• lidé středního věku MeSH
• lidé MeSH
• metformin terapeutické užití   MeSH
• sulfonylmočovinové sloučeniny terapeutické užití   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika MeSH
• Názvy látek
• hypoglykemika MeSH
• metformin MeSH
• sulfonylmočovinové sloučeniny MeSH

The aim of the present pilot pharmacogenetic study was to analyse quantitative effects of sulphonylurea treatment in addition to metformin on parameters of glycemic control with respect to CDKAL1 genotypes in patients with type 2 diabetes. Effect of 6-month sulphonylurea therapy on glycemic control according to CDKAL1 genotypes was evaluated in 101 patients with type 2 diabetes who failed to achieve glycemic control on metformin monotherapy. CDKAL1 rs7756992 polymorphism was determined by melting curve analysis of small amplicon following real-time PCR. After sulphonylurea treatment fasting plasma glucose (FPG) levels were significantly different (p=0.045) among three CDKAL1 genotype groups (AA: n=49; AG: n=36; GG: n=16). In a dominant genetic model, carriers of the G-allele (AG+GG, n=52) achieved significantly lower FPG levels in comparison with patients with the AA genotype (6.90±1.08 vs. 7.48±1.12 mmol/l, p=0.013). Consequently, adjusted ΔFPG was significantly higher in the AG+GG compared to the AA group (1.48±1.51 vs. 1.02±1.33 mmol/l, p=0.022). Similar trend was observed for HbA(1c) levels, but the difference between the genotype groups did not reach the level of statistical significance. Relatively small number of included patients is a limitation of the present study. In conclusion, our results suggest that the magnitude of FPG reduction after 6-month sulphonylurea treatment in patients with type 2 diabetes is related to the variation in CDKAL1.

• MeSH
• cyklin-dependentní kinasa 5 genetika   MeSH
• diabetes mellitus 2. typu farmakoterapie   MeSH
• genetická variace * MeSH
• genotyp MeSH
• hypoglykemika aplikace a dávkování   terapeutické užití   MeSH
• krevní glukóza analýza   MeSH
• lidé středního věku MeSH
• lidé MeSH
• metformin aplikace a dávkování   terapeutické užití   MeSH
• senioři MeSH
• sulfonylmočovinové sloučeniny aplikace a dávkování   terapeutické užití   MeSH
• tRNA-methyltransferasy MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• CDKAL1 protein, human MeSH Prohlížeč
• cyklin-dependentní kinasa 5 MeSH
• hypoglykemika MeSH
• krevní glukóza MeSH
• metformin MeSH
• sulfonylmočovinové sloučeniny MeSH
• tRNA-methyltransferasy MeSH

The author briefly recapitulates the physiology of insulin secretion and pathophysiology with type II diabetes mellitus. Besides sulfonylurea secretagogues and glinides practically used in the long term, the author points out new possibilities of influencing insulin secretion by way of incretin mimetics and gliptins.

• MeSH
• diabetes mellitus 2. typu farmakoterapie   patofyziologie   MeSH
• glukagonu podobný peptid 1 farmakologie   terapeutické užití   MeSH
• glukosa metabolismus   MeSH
• inkretiny farmakologie   terapeutické užití   MeSH
• inzulin metabolismus   MeSH
• lidé MeSH
• sekrece inzulinu MeSH
• sulfonylmočovinové sloučeniny farmakologie   terapeutické užití   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• glukagonu podobný peptid 1 MeSH
• glukosa MeSH
• inkretiny MeSH
• inzulin MeSH
• sulfonylmočovinové sloučeniny MeSH

The authors evaluate treatment by a combination of insulin and gliquidone (Glurenorm) in 29 type 2 diabetics where long-term treatment with oral antidiabetics alone had failed. Within four months all patients were completely compensated from the metabolic aspect. HbA1c declined from 10.8 to 6.5, C peptide, on the other hand, increased from the original value of 1.2 ng/ml to 1.8 ng/ml. The authors did not observe any undesirable effects or hypoglycaemic states. Gliquidone is suitable for combined treatment because of its short-term effect; stimulation of endogenous secretion has a pulsed character and imitates an intensified regime. The prerequisite of success is a low dose of intermediary insulin to prevent inhibition of the central action of gliquidone.

• MeSH
• diabetes mellitus 2. typu krev   farmakoterapie   MeSH
• dospělí MeSH
• hypoglykemika terapeutické užití   MeSH
• krevní glukóza analýza   MeSH
• lidé středního věku MeSH
• lidé MeSH
• senioři MeSH
• sulfonylmočovinové sloučeniny terapeutické užití   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• anglický abstrakt MeSH
• časopisecké články MeSH
• Názvy látek
• gliquidone MeSH Prohlížeč
• hypoglykemika MeSH
• krevní glukóza MeSH
• sulfonylmočovinové sloučeniny MeSH

The effectiveness and tolerance of the new sulphonyl urea antidiabetic gliquidone (commercial name Glurenorm) was tested by three-month administration of this preparation in a group of 39 type 2 diabetics. Gliquidone proved a medium-strength beta-cytotropic antidiabetic preparation. As to side-effects, the authors noted only dyspepsia in one patient (2.5%). Symptomatic hypoglycaemia did not develop in any of the patients. In the subgroup of six patients with diabetic nephropathy the indicators of renal functions did not deteriorate. In a sub-group of 6 patients with concurrent hepatopathy the originally elevated gamma-glutamyl transpeptidase activity receded. The authors confirmed thus the good tolerance of gliquidone in diabetes associated with nephropathy and diabetes with hepatopathy.

• MeSH
• diabetes mellitus 2. typu krev   farmakoterapie   MeSH
• dospělí MeSH
• hypoglykemika škodlivé účinky   terapeutické užití   MeSH
• lidé středního věku MeSH
• lidé MeSH
• senioři MeSH
• sulfonylmočovinové sloučeniny škodlivé účinky   terapeutické užití   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• anglický abstrakt MeSH
• časopisecké články MeSH
• klinické zkoušky MeSH
• multicentrická studie MeSH
• Názvy látek
• gliquidone MeSH Prohlížeč
• hypoglykemika MeSH
• sulfonylmočovinové sloučeniny MeSH