Background: After injuries, infections, or tumor removal, endogenous healing depends on bone repair. Disorders of bone healing are difficult to treat in clinical settings. There are numerous induced methods for correcting bone abnormalities, such as the induced membrane technique, allogenic bone grafting, synthetic bone grafting, artificial joint replacement, and autologous bone grafting. However, the delivery of the bone graft and bone filling materials necessitates surgical implantation at the fracture site, which could cause edema, infection, and the development of heterotopic bone locally. Therefore, systemically administered osteogenic drugs will provide an excellent method for bone lesion healing. Aim of the study: to evaluate the systemic effect of metformin on bone healing after surgical induction of bony defect and to determine the amount of newly formed bone using histological, histomorphometric analysis, and the surface area measurement of newly formed bone. Also to study the safety of metformin administration at the administered dose for this purpose. Materials and methods: Twenty mature male New Zealand rabbits were separated into two groups, each including ten rabbits for the study. The same surgical procedure was performed on all rabbits. Two holes were made at the femur (3 mm in diameter and 3 mm in depth) and left empty. Metformin tablets were ground into a fine powder and the resultant powder was dissolved in 10ml of water to prepare a liquid dosage containing 50 mg /1ml of metformin. Metformin is administered orally to the rabbits through a feeding tube at a dose of 50 mg/kg body weight. Animals were euthanized at two-time intervals, 14 and 28 days. The femur was separated, sectioned preserved, and sent for histological analysis and histomor-phometry. Results: The results revealed that there is an increase in new bone formation and bone-forming cells in the metformin-treated group. Conclusion: Metformin increases bone healing by increasing the number of bone-forming cells and the surface area of newly formed bone tissues and causes less inflammatory response at the site of a bone lesion. So it possesses an osteogenic effect.
Důsledná metabolická kompenzace je zásadní pro úspěšný průběh těhotenství žen s pregestačním i gestačním diabetem. Na rozdíl od období mimo těhotenství jsou však farmakologické možnosti léčby diabetu těhotných žen značně omezené. V porovnání s inzulinem přináší metformin řadu praktických výhod, jako je perorální způsob podání, nenáročná edukace pacientek a nízká finanční náročnost léčby. Přestože prochází placentou, není patrně jeho užívání spojeno s rizikem poškození plodu v časném období těhotenství. Velké randomizované studie naznačují několik pozitivních metabolických důsledků užívání metforminu v těhotenství, jako je nižší přírůstek hmotnosti matky, nižší výskyt hypertenzních poruch těhotných žen nebo menší počet hypertrofických novorozenců. Na druhou stranu je však metformin také spojován s možným rizikem růstové restrikce plodů a předčasného porodu. Ve srovnání s inzulinem nevedl metformin ke snížení rizika závažných novorozeneckých komplikací. V neposlední řadě je zkoumáno možné intrauterinní ovlivnění metabolismu plodu, které může vést ke zvýšenému riziku metabolických poruch v pozdějším životě dětí.
Excelent metabolic control is essential for the successful course of pregnancy in women with both pregestational and gestational diabetes. However, in contrast to the non-pregnancy period, pharmacological options for the treatment of diabetes are limited. Compared with insulin, metformin offers a number of practical advantages, such as an oral route of administration, easy training and the low price. Although it crosses the placenta, its use is probably not associated with a risk of fetal harm in early pregnancy. Large randomized trials suggest several positive metabolic consequences of metformin use in pregnancy. These include lower maternal weight gain, lower incidence of hypertensive disorders in pregnant women, or fewer hypertrophic newborns. On the other hand, metformin is also associated with a possible risk of fetal growth restriction and preterm birth. Compared with insulin, metformin does not reduce the incidence of serious neonatal complications. Finally, the possible intrauterine influence on fetal metabolism, which may lead to an increased risk of metabolic disorders in later life in children, is being investigated.
- MeSH
- diabetes mellitus 2. typu farmakoterapie MeSH
- gestační diabetes farmakoterapie MeSH
- hodnocení léčiv MeSH
- hypoglykemika MeSH
- inzulin terapeutické užití MeSH
- klinické zkoušky jako téma MeSH
- lidé MeSH
- metformin * farmakologie terapeutické užití MeSH
- těhotenství při diabetu * farmakoterapie MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- práce podpořená grantem MeSH
Dlhodobé sledovanie liečby metformínom u pacientov s diabetes mellitus 2. typu vedie ku ich lepšiemu prežívaniu. Multicentrická štúdia v 4 centrách Spojeného kráľovstva v období rokov 2016–2021 sledovala mikrovaskulárnu funkciu koronárnych artérií vo vzťahu k liečbe metformínom. Významné zlepšenie rezervy perfúzie myokardu viedlo k priaznivému ovplyvneniu prognózy a zlepšeniu prežívania pacientov s diabetes mellitus 2. typu. Meranie perfúznej rezervy myokardu sa ukázalo byť lepším ukazovateľom pre endotelovú funkciu v tejto skupine pacientov než meranie prietoku krvi v myokarde.
Longitudinal monitoring of metformin treatment of patients with type-2 diabetes mellitus leads to the improvement of their survival. Multicentric follow-up in four centers of the United Kingdom during years 2016–2021 evaluated coronary microvascular function in relation to the metformin therapy. Significant improvement of myocardial perfusion reserve lead to better prognosis of the patients with type-2 diabetes mellitus. Measurement of myocardial perfusion reserve is the better measure for endothelial function, than myocardial perfusion flow.
- MeSH
- diabetes mellitus 2. typu farmakoterapie komplikace MeSH
- koronární cirkulace MeSH
- lidé MeSH
- metformin * aplikace a dávkování terapeutické užití MeSH
- multicentrické studie jako téma MeSH
- rizikové faktory kardiovaskulárních chorob MeSH
- zobrazování myokardiální perfuze metody MeSH
- Check Tag
- lidé MeSH
AIM: Retrospective national sub-analysis of antidiabetic pharmacotherapy in patients with diabetes mellitus (DM) and heart failure (HF) based on data reported to the National Register of Paid Health Services in the Czech Republic between 2012-2018. METHODOLOGY AND RESULTS: In 2012, there were 75,022 patients with HF and DM (i.e. 42.5% of patients with HF), 6 years later 117,265 (i.e. 41.0% of HF patients in 2018). The most represented antidiabetic drug was metformin (45.6%). Of the insulins and analogues, glargine showed the largest positive trend (5.8% 2012; 14.8% 2018). Empagliflozin was the most prescribed SGLT-2 inhibitor (1.8% in 2018). A decrease in prescribing was observed for saxagliptin (0.5% 2012; 0.1% 2018) and for sulfonylurea derivates - gliclazide (13.0% 2012; 10.3% in 2018) and glimepiride (12.9% 2012; 9.0% 2018). Linagliptin was the most prescribed dipeptidyl peptidase inhibitor (0.7% 2012; 6.8% 2018). CONCLUSION: In the Czech Republic, between 2012 and 2008, there was an increase in prevalence of patients with heart failure and concomitant diabetes mellitus, their proportion being similar. In correspondence with other registries, metformin was used mostly. A positive trend was observed in prescription of DDP-4 and SGLT-2 inhibitors, while there was a significant decrease in patients taking sulfonylureas.
- MeSH
- diabetes mellitus 2. typu * komplikace farmakoterapie MeSH
- glifloziny * terapeutické užití MeSH
- hypoglykemika terapeutické užití MeSH
- inhibitory dipeptidylpeptidasy 4 * terapeutické užití farmakologie MeSH
- lidé MeSH
- metformin * škodlivé účinky MeSH
- retrospektivní studie MeSH
- srdeční selhání * farmakoterapie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- MeSH
- diabetes mellitus 2. typu * farmakoterapie MeSH
- fixní kombinace léků MeSH
- lidé MeSH
- metformin farmakologie terapeutické užití MeSH
- nealkoholová steatóza jater prevence a kontrola MeSH
- pioglitazon farmakologie terapeutické užití MeSH
- randomizované kontrolované studie jako téma MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- komentáře MeSH
- souhrny MeSH
A case study on Sitagliptin drug products and Sitagliptin/Metformin drug products concerning contamination with N-nitrosamines was performed using two newly developed analytical methods for determination of N-nitroso-triazolopyrazine (NTTP; 7-nitroso-3-(trifluoromethyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazine) and its precursor triazolopyrazine (3-(trifluoromethyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazine). The method for determination of triazolopyrazine was previously unpublished, the method for determination of NTTP was published only for analysis of active pharmaceutical ingredient Sitagliptin and not the drug forms. Solving the N-nitrosamine contamination is requested by regulatory authorities all over the world and thus is vital for all pharmaceutical companies. The solution always requires a sensitive analytical method. Both newly developed methods use liquid chromatography coupled with mass spectrometry (single quadrupole analyzer in case of triazolopyrazine and triple quadrupole analyzer in case of NTTP). Separation of triazolopyrazine was achieved on a column Acquity CSH C18 using a mobile phase consisting of aqueous ammonium formate buffered at pH 4.2 and acetonitrile. Detection was performed using positive electrospray and selected ion monitoring at m/z 193. Separation of NTTP was achieved on a column Acquity HSS T3 using a mobile phase consisting of 0.1 % formic acid in water and methanol. Detection was performed using positive electrospray and multiple reaction monitoring at transitions m/z 222.15→42.05 (collision energy 17 eV) and m/z 222.15→192.15 (collision energy 11 eV). Two issues specific to NTTP and triazolopyrazine previously not described in scientific literature were successfully troubleshooted. Spontaneous degradation of Sitagliptin to triazolopyrazine and methyl (R)-3-amino-4-(2,4,5-trifluorophenyl)butanoate was solved by using N,N-dimethylformamide as sample solvent during development of the method for quantitation of triazolopyrazine. A bad peak shape of NTTP due to the presence of rotamers of NTTP was successfully troubleshooted by increasing column temperature. Both methods were used during an optimization study of manufacturing of Sitagliptin and Sitagliptin/Metformin drug products. The goal of the study was to decrease NTTP content in the final drug product under the strict legislative limit set by Federal Drug Agency. The efficacy of several solutions was proven, but could not be fully disclosed due to Intellectual Property Protection policy of Zentiva. Instead, a brief review of recently published strategies to cope with N-nitrosamine contamination is presented.
BACKGROUND: Despite the improvements in treatment over the last decades, periodontal disease (PD) affects millions of people around the world and the only treatment available is based on controlling microbial load. Diabetes is known to increase the risk of PD establishment and progression, and recently, glucose metabolism modulation by pharmaceutical or dietarian means has been emphasised as a significant modulator of non-communicable disease development. METHODS: The impact of pharmaceutically controlling glucose metabolism in non-diabetic animals and humans (REBEC, UTN code: U1111-1276-1942) was investigated by repurposing Metformin, as a mean to manage periodontal disease and its associated systemic risk factors. RESULTS: We found that glucose metabolism control via use of Metformin aimed at PD management resulted in significant prevention of bone loss during induced periodontal disease and age-related bone loss in vivo. Metformin also influenced the bacterial species present in the oral environment and impacted the metabolic epithelial and stromal responses to bacterial dysbiosis at a single cell level. Systemically, Metformin controlled blood glucose levels and age-related weight gain when used long-term. Translationally, our pilot randomized control trial indicated that systemic Metformin was safe to use in non-diabetic patients and affected the periodontal tissues. During the medication window, patients showed stable levels of systemic blood glucose, lower circulating hsCRP and lower insulin levels after periodontal treatment when compared to placebo. Finally, patients treated with Metformin had improved periodontal parameters when compared to placebo treated patients. CONCLUSION: This is the first study to demonstrate that systemic interventions using Metformin in non-diabetic individuals aimed at PD prevention have oral-systemic effects constituting a possible novel form of preventive medicine for oral-systemic disease management.
- MeSH
- diabetes mellitus 2. typu * MeSH
- hypoglykemika farmakologie terapeutické užití MeSH
- krevní glukóza MeSH
- lidé MeSH
- management nemoci MeSH
- metformin * farmakologie terapeutické užití MeSH
- nemoci parodontu * farmakoterapie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- randomizované kontrolované studie MeSH
x
x
- MeSH
- dítě MeSH
- lidé MeSH
- liraglutid farmakologie terapeutické užití MeSH
- metformin farmakologie terapeutické užití MeSH
- obezita dětí a dospívajících * etiologie terapie MeSH
- pohybová aktivita MeSH
- průzkumy a dotazníky MeSH
- rizikové faktory MeSH
- stravovací zvyklosti MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- MeSH
- bariatrická chirurgie metody MeSH
- dítě MeSH
- lidé MeSH
- liraglutid farmakologie terapeutické užití MeSH
- metformin farmakologie terapeutické užití MeSH
- obezita dětí a dospívajících * chirurgie farmakoterapie MeSH
- průzkumy a dotazníky statistika a číselné údaje MeSH
- žaludeční bypass metody MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- Publikační typ
- přehledy MeSH
BACKGROUND: Concomitant medications may potentially affect the outcome of cancer patients. In this sub-analysis of the ARON-2 real-world study (NCT05290038), we aimed to assess the impact of concomitant use of proton pump inhibitors (PPI), statins, or metformin on outcome of patients with metastatic urothelial cancer (mUC) receiving second-line pembrolizumab. METHODS: We collected data from the hospital medical records of patients with mUC treated with pembrolizumab as second-line therapy at 87 institutions from 22 countries. Patients were assessed for overall survival (OS), progression-free survival (PFS), and overall response rate. We carried out a survival analysis by a Cox regression model. RESULTS: A total of 802 patients were eligible for this retrospective study; the median follow-up time was 15.3 months. PPI users compared to non-users showed inferior PFS (4.5 vs. 7.2 months, p = 0.002) and OS (8.7 vs. 14.1 months, p < 0.001). Concomitant PPI use remained a significant predictor of PFS and OS after multivariate Cox analysis. The use of statins or metformin was not associated with response or survival. CONCLUSIONS: Our study results suggest a significant prognostic impact of concomitant PPI use in mUC patients receiving pembrolizumab in the real-world context. The mechanism of this interaction warrants further elucidation.
