Obezita se stala v posledních 30 letech celosvětovou pandemií. V léčbě obezity se v současnosti uplatňuje především úprava životního stylu, která však mnohdy dlouhodobě selhává. Pro příští desetiletí se jako perspektivní jeví v léčbě obezity spolu s chirurgickou léčbou dlouhodobé podávání antiobezitik, tedy léků, které příznivě ovlivňují nejen pokles nadměrné hmotnosti, ale i zdravotní rizika spojená s obezitou. Tento text podává přehled o současných možnostech farmakoterapie obezity včetně jejich indikací, vhodném výběru pacienta a nežádoucích účincích léčby. Přináší také přehled studií, které prokazují dlouhodobou účinnost a bezpečnost této léčby. Přesto, že účinná a bezpečná antiobezitika jsou v současné době k dispozici, není tato léčba ani částečně hrazena ze všeobecného zdravotního pojištění. Náklady na léčbu jsou však pro velkou část obézních dlouhodobě neúnosné. Faktická nedostupnost účinných antiobezitik pro indikované pacienty má závažné zdravotně-ekonomické dopady. Nevyužívání účinných možností léčby, potvrzených postupy medicíny založené na důkazech, má za následek vysokou prevalenci s obezitou spojených nemocí, jejichž léčení je ekonomicky ještě nákladnější a v případě diabetes mellitus 2. typu dokonce méně efektivní. Jsme přesvědčeni, že alespoň částečná úhrada antiobezitik z prostředků všeobecného zdravotního pojištění pro pacienty s prokázanou compliance a za jasně vymezených podmínek je nezbytným krokem ke zlepšení situace a ve svých důsledcích bude jednoznačně ekonomicky prospěšná.
Obesity has become a worldwide pandemic in the last thirty years. Its treatment is primarily based on the life-style changes that, however, often fail in the long-term run. For the next decade, major perspectives in the successful obesity treatment include, in addition to bariatric surgery, a long-term treatment with anti-obesity drugs, in particular the ones that in addition to weight reduction also directly affect obesity-related pathologies. This paper summarizes current possibilities of obesity pharmacotherapy including its indication, proper selection of patients and side effects of anti-obesity drugs. It also reviews the studies describing long-term efficacy and safety of anti-obesity drugs. Despite the availability of efficacious and safe anti-obesity drugs, these therapies are not even partially covered by health insurance. The costs of anti-obesity drugs are for the majority of patients with obesity unacceptably high. The actual unavailability of anti-obesity drugs for patients with obesity has significant health-economic consequences. Limited use of these medications that have evidence-based data supporting their efficacy, contributes to high prevalence of obesity-related pathologies with subsequent low treatment efficacy and high treatment costs. We believe that at least partial reimbursement of anti-obesity drugs from general health insurance, in patients with verified compliance and under clearly defined conditions, is a necessary step to improve this situation which could lead to clearly economically effective results.
- MeSH
- hodnocení léčiv MeSH
- kombinovaná farmakoterapie MeSH
- látky proti obezitě aplikace a dávkování klasifikace terapeutické užití MeSH
- léčba obezity * MeSH
- lidé MeSH
- liraglutid aplikace a dávkování farmakologie terapeutické užití MeSH
- náklady na léky MeSH
- nežádoucí účinky léčiv MeSH
- obezita * farmakoterapie MeSH
- rizikové faktory MeSH
- Check Tag
- lidé MeSH
- MeSH
- endokrinologie * MeSH
- lidé MeSH
- molekulární biologie * MeSH
- periodika jako téma * MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- úvodníky MeSH
Objective: The increasing prevalence of obesity is expected to promote the demand for endocrine testing. To facilitate evidence guided testing, we aimed to assess the prevalence of endocrine disorders in patients with obesity. The review was carried out as part of the Endocrine Work-up for the Obesity Guideline of the European Society of Endocrinology. Design: Systematic review and meta-analysis of the literature. Methods: A search was performed in MEDLINE, EMBASE, Web of Science and COCHRANE Library for original articles assessing the prevalence of hypothyroidism, hypercortisolism, hypogonadism (males) or hyperandrogenism (females) in patients with obesity. Data were pooled in a random-effects logistic regression model and reported with 95% confidence intervals (95% CI). Results: Sixty-eight studies were included, concerning a total of 19.996 patients with obesity. The pooled prevalence of overt (newly diagnosed or already treated) and subclinical hypothyroidism was 14.0% (95% CI: 9.7-18.9) and 14.6% (95% CI: 9.2-20.9), respectively. Pooled prevalence of hypercortisolism was 0.9% (95% CI: 0.3-1.6). Pooled prevalence of hypogonadism when measuring total testosterone or free testosterone was 42.8% (95% CI: 37.6-48.0) and 32.7% (95% CI: 23.1-43.0), respectively. Heterogeneity was high for all analyses. Conclusions: The prevalence of endocrine disorders in patients with obesity is considerable, although the underlying mechanisms are complex. Given the cross-sectional design of the studies included, no formal distinction between endocrine causes and consequences of obesity could be made.
The mechanisms behind the cardiovascular and renal benefits of empagliflozin is not fully understood. The positive impact of the medication on cardiovascular mortality can not be solely attributed to its antidiabetic effect, with a metabolic mechanism possibly involved. To investigate the metabolic effects of empagliflozin treatment (10 mg/kg/day for 6 weeks), we used an adult male rat model with serious vascular complications associated with metabolic syndrome and prediabetes. Impaired glucose tolerance, severe albuminuria and impaired insulin sensitivity were induced by intragastric administration of methylglyoxal and high sucrose diet feeding for four months. Although empagliflozin decreased body weight, non-fasting glucose and insulin, glucagon levels remained unchanged. In addition, empagliflozin increased adiponectin levels (+40%; p < 0.01) and improved skeletal muscle insulin sensitivity. Increased non-esterified fatty acids (NEFA) in empagliflozin-treated rats is understood to generate ketone bodies. Empagliflozin increased β-hydroxybutyrate levels in serum (+66%; p < 0.05) and the myocardium (30%; p < 0.01), suggesting its possible involvement as an alternative substrate for metabolism. Empagliflozin switched substrate utilisation in the myocardium, diverting glucose oxidation to fatty acid oxidation. Representing another favorable effect, empagliflozin also contributed to decreased uric acid plasma levels (-19%; p < 0.05). In the kidney cortex, empagliflozin improved oxidative and dicarbonyl stress parameters and increased gene expression of β-hydroxybutyrate dehydrogenase, an enzyme involved in ketone body utilisation. In addition, empagliflozin decreased microalbuminuria (-27%; p < 0.01) and urinary neutrophil gelatinase-associated lipocalin (NGAL) excretion (-29%; p < 0.01). Our results reveal the important systemic metabolic effect of empagliflozin on alterations in substrate utilisation and on increased ketone body use in prediabetic rats. Improved oxidative and dicarbonyl stress and decreased uric acid are also possibly involved in the cardio- and reno-protective effects of empagliflozin.
- MeSH
- benzhydrylové sloučeniny farmakologie MeSH
- glukosa metabolismus MeSH
- glukosidy farmakologie MeSH
- inzulinová rezistence MeSH
- ketolátky metabolismus MeSH
- krysa rodu rattus MeSH
- ledviny účinky léků metabolismus MeSH
- modely nemocí na zvířatech MeSH
- ochranné látky farmakologie MeSH
- oxidační stres účinky léků MeSH
- potkani Wistar MeSH
- prediabetes farmakoterapie metabolismus MeSH
- srdce účinky léků MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Obesity is an emerging condition, with a prevalence of ~20%. Although the simple measurement of BMI is likely a simplistic approach to obesity, BMI is easily calculated, and there are currently no data showing that more sophisticated methods are more useful to guide the endocrine work-up in obesity. An increased BMI leads to a number of hormonal changes. Additionally, concomitant hormonal diseases can be present in obesity and have to be properly diagnosed - which in turn might be more difficult due to alterations caused by body fatness itself. The present European Society of Endocrinology Clinical Guideline on the Endocrine Work-up in Obesity acknowledges the increased prevalence of many endocrine conditions in obesity. It is recommended to test all patients with obesity for thyroid function, given the high prevalence of hypothyroidism in obesity. For hypercortisolism, male hypogonadism and female gonadal dysfunction, hormonal testing is only recommended if case of clinical suspicion of an underlying endocrine disorder. The guideline underlines that weight loss in obesity should be emphasized as key to restoration of hormonal imbalances and that treatment and that the effect of treating endocrine disorders on weight loss is only modest.
AIM: To evaluate the efficacy and safety of twice-daily insulin degludec/insulin aspart vs. twice-daily biphasic insulin aspart 30 in people with Type 2 diabetes mellitus who were naïve to insulin. METHODS: In this 26-week, multinational, open-label, controlled, two-arm, parallel-group, treat-to-target trial, participants [mean (± sd) age 58.9 (±8.9) years, duration of diabetes 9.5 (±5.9) years, HbA1c 68 (±8.7) mmol/mol or 8.4 (±0.8)% and BMI 31.2 (±4.2) kg/m(2) ) were randomized (1:1) to insulin degludec/insulin aspart (n = 197) or biphasic insulin aspart 30 (n = 197), administered with breakfast and the main evening meal, titrated to a self-monitored plasma glucose target > 3.9 and ≤ 5.0 mmol/l. RESULTS: The mean HbA1c was reduced to 49 mmol/mol (6.6%) with insulin degludec/insulin aspart and 48 mmol/mol (6.5%) with biphasic insulin aspart 30. Insulin degludec/insulin aspart achieved the prespecified non-inferiority margin (estimated treatment difference 0.02%; 95% CI -0.12, 0.17). Insulin degludec/insulin aspart was superior in lowering fasting plasma glucose (estimated treatment difference -1.00 mmol/l; 95% CI -1.4, -0.6; P < 0.001) and reducing overall and nocturnal confirmed hypoglycaemia at a similar overall insulin dose compared with biphasic insulin aspart 30. Similar proportions of participants in each arm experienced severe hypoglycaemia. Adverse events were equally distributed. CONCLUSIONS: Consistent with previous findings, insulin degludec/insulin aspart twice daily effectively improved long-term glycaemic control, with superior reductions in FPG, and significantly less overall and nocturnal confirmed hypoglycaemia compared with biphasic insulin aspart 30 in people with Type 2 diabetes who were insulin-naïve.
- MeSH
- bifázický inzulin aplikace a dávkování škodlivé účinky terapeutické užití MeSH
- diabetes mellitus 2. typu krev farmakoterapie MeSH
- dlouhodobě působící inzulin aplikace a dávkování škodlivé účinky chemie terapeutické užití MeSH
- fixní kombinace léků MeSH
- glykovaný hemoglobin analýza MeSH
- hyperglykemie prevence a kontrola MeSH
- hypoglykemie chemicky indukované epidemiologie patofyziologie prevence a kontrola MeSH
- hypoglykemika aplikace a dávkování škodlivé účinky chemie terapeutické užití MeSH
- inzulin aspart aplikace a dávkování škodlivé účinky terapeutické užití MeSH
- jídla MeSH
- krevní glukóza analýza MeSH
- lidé středního věku MeSH
- lidé MeSH
- monitorování léčiv MeSH
- NPH inzulin aplikace a dávkování škodlivé účinky terapeutické užití MeSH
- riziko MeSH
- rozpustnost MeSH
- rozvrh dávkování léků MeSH
- selfmonitoring glykemie MeSH
- senioři MeSH
- stupeň závažnosti nemoci MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- práce podpořená grantem MeSH
- randomizované kontrolované studie MeSH
- srovnávací studie MeSH
OBJECTIVES: Obesity is a frequent metabolic disorder but an effective therapy is still scarce. Anorexigenic neuropeptides produced and acting in the brain have the potential to decrease food intake and ameliorate obesity but are ineffective after peripheral application. We have designed lipidized analogs of prolactin-releasing peptide (PrRP), which is involved in energy balance regulation as demonstrated by obesity phenotypes of both PrRP- and PrRP-receptor-knockout mice. RESULTS: Lipidized PrRP analogs showed binding affinity and signaling in PrRP receptor-expressing cells similar to natural PrRP. Moreover, these analogs showed high binding affinity also to anorexigenic neuropeptide FF-2 receptor. Peripheral administration of myristoylated and palmitoylated PrRP analogs to fasted mice induced strong and long-lasting anorexigenic effects and neuronal activation in the brain areas involved in food intake regulation. Two-week-long subcutaneous administration of palmitoylated PrRP31 and myristoylated PrRP20 lowered food intake, body weight and improved metabolic parameters, and attenuated lipogenesis in mice with diet-induced obesity. CONCLUSIONS: Our data suggest that the lipidization of PrRP enhances stability and mediates its effect in central nervous system. Strong anorexigenic and body-weight-reducing effects make lipidized PrRP an attractive candidate for anti-obesity treatment.
- MeSH
- energetický metabolismus MeSH
- hormon uvolňující prolaktin analogy a deriváty farmakologie MeSH
- látky proti obezitě farmakologie MeSH
- lipidy chemie MeSH
- myši inbrední C57BL MeSH
- myši MeSH
- obezita prevence a kontrola MeSH
- poločas MeSH
- přijímání potravy MeSH
- regulace chuti k jídlu MeSH
- signální transdukce MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
The only peripherally released orexigenic hormone, ghrelin, plays a key role in food intake and body weight regulation. Antagonizing the ghrelin receptor, GHS-R1a, represents a promising approach for anti-obesity therapy. In our study, two novel GHS-R1a antagonists JMV4208 and JMV3002, which are trisubstituted 1,2,4-triazoles, decreased food intake in fasted lean mice in a dose-dependent manner, with ED50 values of 5.25 and 2.05 mg/kg, respectively. Both compounds were stable in mouse blood, with half-lives of 90 min (JMV4208) and 60 min (JMV3002), and disappeared from the blood 8h after administration. Fourteen days of treatment with the ghrelin antagonists (20 mg/kg twice a day) decreased food intake, body weight and adipose tissue mass in mice with diet-induced obesity (DIO). These results are likely attributable to an impact on food intake reduction and an attenuated expression of the lipogenesis-promoting enzymes (acetyl-CoA carboxylase 1 in subcutaneous fat and fatty acid synthase in subcutaneous and intraperitoneal fat). The decrease in fat mass negatively impacted circulating leptin levels. These data suggest that JMV4208 and JMV3002 could be useful therapeutic agents for the treatment of obesity.
- MeSH
- kyseliny pikolinové chemie farmakologie MeSH
- myši inbrední C57BL MeSH
- myši MeSH
- přijímání potravy účinky léků MeSH
- receptory ghrelinu antagonisté a inhibitory MeSH
- tělesná hmotnost účinky léků MeSH
- triazoly chemie farmakologie MeSH
- tuková tkáň účinky léků MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
OBJECTIVE: Fibroblast growth factor (FGF)-19 and FGF-21 are novel metabolic regulators that improve insulin resistance and obesity in rodents. The aim of the study was to assess the effects of laparoscopic sleeve gastrectomy (LSG) on serum concentrations of FGF-19 and FGF-21 along with circulating bile acids and other relevant hormonal and biochemical parameters. DESIGN AND METHODS: Seventeen females with obesity undergoing LSG and 15 lean healthy females were included into the study. Anthropometric and biochemical parameters, serum concentrations of FGF-19 and -21, insulin, adiponectin, leptin, C-reactive protein, resistin, amylin (total), ghrelin (active), glucagon-like peptide 1 (GLP-1, active), glucose-dependent insulinotropic peptide (GIP, total), peptide YY (PYY, total), pancreatic polypeptide (PP), and bile acids, and mRNA expression of selected adipokines and inflammatory markers in bioptic samples of subcutaneous fat were assessed at baseline and 6, 12, and 24 months after LSG. RESULTS: LSG markedly decreased body weight, BMI, waist circumference, and insulin levels and improved systemic inflammation and lipid levels. FGF-19 concentrations increased and FGF-21 concentrations decreased after LSG along with increased adiponectin and decreased leptin, amylin, and ghrelin levels. GLP-1, GIP, PP, and circulating bile acids were not affected by LSG. PYY decreased significantly 24 months after surgery only. mRNA expression analysis in subcutaneous fat showed markedly reduced proinflammatory state. CONCLUSIONS: Our results indicate that increased FGF-19 and decreased ghrelin concentrations could have partially contributed to the improvement of systemic inflammation and some metabolic parameters after LSG, while changes of FGF-21 are rather secondary because of weight loss.
- MeSH
- adiponektin krev MeSH
- amylin krev MeSH
- C-reaktivní protein metabolismus MeSH
- dospělí MeSH
- fibroblastové růstové faktory krev MeSH
- gastrektomie metody MeSH
- ghrelin krev MeSH
- glukagonu podobný peptid 1 krev MeSH
- hmotnostní úbytek MeSH
- index tělesné hmotnosti MeSH
- inzulin krev MeSH
- inzulinová rezistence MeSH
- leptin krev MeSH
- lidé středního věku MeSH
- lidé MeSH
- messenger RNA metabolismus MeSH
- morbidní obezita krev chirurgie MeSH
- obvod pasu MeSH
- pankreatický polypeptid krev MeSH
- peptid YY krev MeSH
- podkožní tuk metabolismus MeSH
- prospektivní studie MeSH
- resistin krev MeSH
- žaludeční inhibiční polypeptid krev MeSH
- žlučové kyseliny a soli krev MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
