Sodium-glucose cotranspor ter 2 (SGLT2) inhibitors in nephrolithiasis: should we "gliflozin" patients with kidney stone disease? / Inibidores de cotransportadores sódio-glicose-2 (SGLT2) na nefrolitíase - devemos "gliflozinar" os litiásicos?

ABSTRACT The prevalence of nephrolithiasis is increasing worldwide. Despite advances in understanding the pathogenesis of lithiasis, few studies have demonstrated that specific clinical interventions reduce the recurrence of nephrolithiasis. The aim of this review is to analyze the current data and potential effects of iSGLT2 in lithogenesis and try to answer the question: Should we also "gliflozin" our patients with kidney stone disease?

RESUMO A prevalência da nefrolitíase está aumentando em todo o mundo. Apesar dos avanços na compreensão da patogênese da doença litiásica, poucos estudos demonstraram que intervenções clínicas específicas diminuem a recorrência da nefrolitíase. O objetivo desta revisão é analisar os dados atuais e efeitos potenciais dos iSGLT2 na doença litiásica e tentar responder à pergunta: devemos também "gliflozinar" os litiásicos?

Pathogenic gating pore current conducted by autism-related mutations in the NaV1.2 brain sodium channel.

Autism spectrum disorder (ASD) is a complex neurodevelopmental condition characterized by social and communication deficits and repetitive behaviors. The genetic heterogeneity of ASD presents a challenge to the development of an effective treatment targeting the underlying molecular defects. ASD gating charge mutations in the KCNQ/KV7 potassium channel cause gating pore currents (Igp) and impair action potential (AP) firing of dopaminergic neurons in brain slices. Here, we investigated ASD gating charge mutations of the voltage-gated SCN2A/NaV1.2 brain sodium channel, which ranked high among the ion channel genes with mutations in individuals with ASD. Our results show that ASD mutations in the gating charges R2 in Domain-II (R853Q), and R1 (R1626Q) and R2 (R1629H) in Domain-IV of NaV1.2 caused Igp in the resting state of ~0.1% of the amplitude of central pore current. The R1626Q mutant also caused significant changes in the voltage dependence of fast inactivation, and the R1629H mutant conducted proton-selective Igp. These potentially pathogenic Igp were exacerbated by the absence of the extracellular Mg2+ and Ca2+. In silico simulation of the effects of these mutations in a conductance-based single-compartment cortical neuron model suggests that the inward Igp reduces the time to peak for the first AP in a train, increases AP rates during a train of stimuli, and reduces the interstimulus interval between consecutive APs, consistent with increased neural excitability and altered input/output relationships. Understanding this common pathophysiological mechanism among different voltage-gated ion channels at the circuit level will give insights into the underlying mechanisms of ASD.

Monolithic Interphase Enables Fast Kinetics for High-Performance Sodium-Ion Batteries at Subzero Temperature.

In spite of the competitive performance at room temperature, the development of sodium-ion batteries (SIBs) is still hindered by sluggish electrochemical reaction kinetics and unstable electrode/electrolyte interphase under subzero environments. Herein, a low-concentration electrolyte, consisting of 0.5M NaPF6 dissolving in diethylene glycol dimethyl ether solvent, is proposed for SIBs working at low temperature. Such an electrolyte generates a thin, amorphous, and homogeneous cathode/electrolyte interphase at low temperature. The interphase is monolithic and rich in organic components, reducing the limitation of Na+ migration through inorganic crystals, thereby facilitating the interfacial Na+ dynamics at low temperature. Furthermore, it effectively blocks the unfavorable side reactions between active materials and electrolytes, improving the structural stability. Consequently, Na0.7Li0.03Mg0.03Ni0.27Mn0.6Ti0.07O2//Na and hard carbon//Na cells deliver a high capacity retention of 90.8 % after 900 cycles at 1C, a capacity over 310 mAh g-1 under -30 °C, respectively, showing long-term cycling stability and great rate capability at low temperature.

FeS2 nanosheets-luminol-O2 chemiluminescence method for determination of venlafaxine hydrochloride, imipramine hydrochloride, and cefazolin sodium.

This study introduces a novel chemiluminescence (CL) approach utilizing FeS2 nanosheets (NSs) catalyzed luminol-O2 CL reaction for the measurement of three pharmaceuticals, namely venlafaxine hydrochloride (VFX), imipramine hydrochloride (IPM), and cefazolin sodium (CEF). The CL method involved the phenomenon of quenching induced by the pharmaceuticals in the CL reaction. To achieve the most quenching efficacy of the pharmaceuticals in the CL reaction, the concentrations of reactants comprising luminol, NaOH, and FeS2 NSs were optimized accordingly. The calibration curves demonstrated exceptional linearity within the concentration range spanning from 4.00 × 10-7 to 1.00 × 10-3 mol L-1, 1.00 × 10-7 to 1.00 × 10-4 mol L-1, and 4.00 × 10-6 to 2.00 × 10-4 mol L-1 with detection limits (3σ) of 3.54 × 10-7, 1.08 × 10-8, and 2.63 × 10-6 mol L-1 for VFX, IPM, and CEF, respectively. This study synthesized FeS2 NSs using a facile hydrothermal approach, and then the synthesized FeS2 NSs were subjected to a comprehensive characterization using a range of spectroscopic methods. The proposed CL method was effective in measuring the aforementioned pharmaceuticals in pharmaceutical formulations as well as different water samples. The mechanism of the CL system has been elucidated.

Pulmonary thrombotic pulmonary hypertension managed using antithrombotic and pulmonary vasodilator treatment.

An 8-year-old Leonberger receiving immunosuppressive treatment with clinical signs of acute dyspnea, cyanosis, and difficulty standing was referred to our institution (Day 1). Treatment including oxygen, clopidogrel, and low-molecular-weight heparin was initiated for suspected pulmonary thrombosis. However, exertional dyspnea persisted until Day 10, and increased tricuspid regurgitation velocity, pulmonary vascular resistance, and McConnell's signs also were observed. Thus, beraprost sodium was administered PO on Day 11 to treat suspected pulmonary hypertension. On Day 13, contrast-enhanced computed tomography identified extensive contrast defects in the pulmonary arteries, and IV monteplase was administered on Days 14 and 18, with marked improvement in respiratory status and exertional dyspnea on Day 20. Right ventricular function and McConnell signs also improved, and tricuspid regurgitation velocity and pulmonary vascular resistance decreased. On Day 250, echocardiography indicated further improvement in pulmonary hypertension pathophysiology. The patient was still progressing well with antithrombotic and pulmonary vasodilator treatment 400 days later.

Removal of Cu(II) by sodium hexametaphosphate and nano zero-valent iron modified calcium bentonite: characteristic, adsorption performance and mechanism.

Cu (II) is a toxic heavy metal commonly identified in groundwater contaminants. Bentonite-based cutoff wall is the most used method in isolating and adsorbing contaminants, while the bentonite in it easily to fail due to Cu(II) exchange. This study synthesized a novel material through the modification of calcium bentonite (CaB) utilizing sodium hexametaphosphate (SHMP) and nano zero-valent iron (NZVI). The characteristics, adsorption performance, and mechanism of the NZVI/SHMP-CaB were investigated comprehensively. The results showed that SHMP can disperse CaB and reduce flocculation, while NZVI can be further stabilized without agglomeration. The best adsorption performance of NZVI/SHMP-CaB could be obtained at the dosage of 2% SHMP and 4% NZVI. The NZVI/SHMP-CaB exhibited an outstanding removal efficiency of over 60% and 90% at a high Cu(II) concentration (pH = 6, Cu(II) = 300 mg/L) and acidic conditions (pH = 3-6, Cu(II) = 50 mg/L), respectively. The adsorption of Cu(II) by NZVI/SHMP-CaB followed a pseudo-second-order kinetic model, and fitting results from the Freundlich isothermal model suggested that the adsorption process occurred spontaneously. Besides the rapid surface adsorption on the NZVI/SHMP-CaB and ion exchange with interlayer ions in bentonite, the removal mechanism of Cu(II) also involved the chemical reduction to insoluble forms such as Cu0 and Cu2O. The generated FePO4 covered the surface of the homogenized NZVI particles, enhancing the resistance of NZVI/SHMP-CaB to acidic and oxidative environments. This study indicates that NZVI/SHMP-CaB is a promising alternative material which can be used for heavy metal removal from contaminated soil and water.

Influence of Sodium Chloride on Human Bitter Taste Receptor Responses.

In the past, taste interactions between sodium chloride (NaCl) and bitter tastants were investigated in human sensory studies, and the suppression of bitterness by sodium was observed. It is currently not clear if this phenomenon occurs predominantly peripherally or centrally and if the effect is general or only particular bitter compounds are blocked. Therefore, the influence of NaCl at the receptor level was tested by functional expression assays using four out of ∼25 human bitter taste receptors together with prototypical agonists. It was observed that NaCl affected only the responses of particular bitter taste receptor-compound pairs, whereas other bitter responses remained unchanged upon variations of the sodium concentrations. Among the tested receptors, TAS2R16 showed a reduction in signaling in the presence of NaCl. This demonstrates that for some receptor-agonist pairs, NaCl reduces the activation at the receptor level, whereas central effects may dominate the NaCl-induced bitter taste inhibition for other substances.

Photo trapping voltage-gated cardiac sodium channels: inferring local motions at the 'inactivation gate'.

Rapid and effectual inactivation in voltage-gated sodium channels is required for canonical action-potential firing. This "fast" inactivation arises from swift and reversible protein conformational changes that utilize transmembrane segments and the cytoplasmic linker between channel domains III and IV. Until recently, fast inactivation had been accepted to rely on a "ball and chain" mechanism whereby a hydrophobic triplet of DIII-IV amino acids (IFM) impairs conductance by binding to a site in central pore of the channel made available by channel opening. New structures of sodium channel have upended this model. Specifically, cryo-EM structures of eukaryotic sodium channels depict a peripheral binding site for the IFM motif, outside of the pore, opening the possibility of a yet unidentified allosteric mechanism of fast inactivation gating. We set out to study fast inactivation by photo-trapping human sodium channels in various functional states under voltage control. This was achieved by genetically encoding the cross-linking unnatural amino acid benzophenone-phenylalanine at various sites within the DIII-IV linker in the cardiac sodium channel NaV1.5. These data show dynamic state and positional dependent trapping of the transient conformations associated with fast inactivation, each yielding different phenotypes and rates of trapping. These data reveal distinct conformational changes that underly fast inactivation and point to a dynamic environment around the IFM locus.

Exploring the Efficacy of Sotagliflozin on Heart and Kidney Health in Diabetic Patients: A Comprehensive Meta-Analysis.

Evidence for reducing cardiovascular and renal events with sotagliflozin is uncertain among type 2 diabetes mellitus (T2DM) patients. To gather more evidence, this meta-analysis assesses the beneficial effects of sotagliflozin, a dual sodium-glucose cotransporter 1 and 2 inhibitor, in reducing the cardiovascular and renal events in diabetic patients with or without chronic kidney disease (CKD). Scopus, Google Scholar, Cochrane Central Register of Controlled Trials (CENTRAL), and PubMed were the databases used to search. The studies published from January 1, 2018, to January 30, 2022, were considered. The eligibility of studies was assessed independently. The data were collected in a modified Cochrane data extraction form. The included studies' quality was assessed with the Cochrane risk-of-bias tool. The quality of evidence for renal and cardiovascular outcomes was evaluated using GRADEpro software. The number of events of urgent visits to the hospital and requiring hospitalization was reduced (RR: 0.73; 95% CI: 0.69, 0.78; P value <0.00001). The mortality rate because of cardiovascular events was decreased with sotagliflozin (RR: 0.73; 95% CI: 0.67, 0.80; P value <0.00001). Patients taking sotagliflozin had a drastic decline in the number of deaths due to stroke and non-fatal myocardial infarction. Yet, there is no difference between the groups in terms of changes in mortality due to other causes or the glomerular filtration rate (GFR). Sotagliflozin demonstrated effectiveness in reducing the mortality rate related to heart failure and cardiovascular events when the dose was increased from 200 mg to 400 mg. Despite this, evidence is still needed to prove the renal protective action.

Inhibitory effects of glutathione peroxidase on microbial spoilage of crayfish (Procambarus clarkii) during refrigerated storage.

The variety of enzyme-based biological preservatives is limited. This study evaluated the effects of glutathione peroxidase (GSH-Px) on the quality of crayfish during refrigerated storage by measuring the pH, total volatile basic nitrogen, trimethylamine, and microbial contamination in crayfish muscle simulation system. The results revealed that 0.3% GSH-Px (CK3) not only suppressed the degradation of nitrogenous substances but also decreased the contamination levels of total viable, Enterobacteriaceae, and Pseudomonas counts (P < 0.05). Furthermore, the populations of Lactococcus, Aeromonas, and Massilia differed in the CK3 group compared to the other groups (P < 0.05) at the end of the storage (day 15). Moreover, the principal coordinate analysis showed that the colony composition of CK3 stored for 15 days was similar to that of the control group stored for 10 days. Therefore, GSH-Px exhibits antibacterial activity against Gram-negative bacteria and has good application potential in freshwater aquatic product preservation.

Application of sodium alginate-based edible coating with citric acid to improve the safety and quality of fresh-cut melon (Cucumis melo L.) during cold storage.

The safety and quality of fresh-cut melons is reduced by a series of decay processes by enzymatic browning and microbial contamination. This study aimed to assess the impact of a 2% sodium alginate-based edible coating (ALC) combined with different concentrations of citric acid (CA; 0.5%, 1%, 2%, and 3%) on the microbial safety and physical quality of fresh-cut melons during a 7-day storage period at 10 °C. The findings revealed that the combination of ALC and 3% CA was successful in preventing the growth of pathogenic bacteria (Escherichia coli O157:H7, Salmonella spp., Listeria monocytogenes, and Staphylococcus aureus) and natural microflora on fresh-cut melons during storage. In addition, treating fresh-cut melons with ALC containing 3% CA improved their quality by reducing browning and softening during storage at 10 °C. Based on these findings, it can be concluded that using ALC with 3% CA is an effective method to improve the safety and quality of fresh-cut melons.

Relationship between microstructure formation and in vitro starch digestibility in baked gluten-starch matrices.

Increased prevalence of diabetes prompts the development of foods with reduced starch digestibility. This study analyzed the impact of adding soluble dietary fiber (inulin-IN; polydextrose-PD) to baked gluten-starch matrices (7.5-13%) on microstructure formation and in vitro starch digestibility. IN and PD enhanced water-holding capacity, the hardness of baked matrices, and lowered water activity in the formulated matrices, potentially explaining the reduced starch gelatinization degree as IN or PD concentration increased. A maximum gelatinization decrease (26%) occurred in formulations with 13% IN. Micro-CT analysis showed a reduction in total and open porosity, which, along with the lower gelatinization degree, may account for the reduced in vitro starch digestibility. Samples with 13% IN exhibited a significantly lower rapidly available glucose fraction (8.56 g/100 g) and higher unavailable glucose fraction (87.76 g/100 g) compared to the control (34.85 g/100 g and 47.59 g/100 g, respectively). These findings suggest the potential for developing healthier, starch-rich baked foods with a reduced glycemic impact.

Antimicrobial efficacy of two commercially available herbal products with and without ultrasonic activation in primary endodontic infections: A randomized clinical trial.

Background: Effective irrigation is crucial for successful endodontic treatment. Traditional irrigants like sodium hypochlorite (NaOCl) have been widely used, but there is a growing interest in exploring natural alternatives for their potential antimicrobial properties. Objective: The study aims to compare the antimicrobial efficacy of Neem, Bitter Gourd, and NaOCl, with and without ultrasonic activation in managing primary endodontic infections. Materials and Methods: Ninety patients were randomly assigned six groups (n = 15) Group 1: NaOCl, Group 2: NaOCl with passive ultrasonic irrigation (PUI), Group 3: Neem juice, Group 4: Neem juice with PUI, Group 5: Bitter gourd juice, and Group 6: Bitter gourd juice with PUI. Bacteriological samples were collected before (S1) and after (S2) shaping, plated on brain heart infusion agar, and colony counting was done after 24 h. Statistical Analysis Used: Shapiro-Wilk test, one-way ANOVA, post hoc Tukey analysis, and paired t-test. Results: All the groups demonstrated a significant reduction in bacterial count. Groups with PUI (2, 4, 6) demonstrated higher mean bacterial reduction than their counterparts without PUI (1, 3, 5). Conclusion: Neem and Bitter gourd juices, particularly when used with PUI, demonstrated antimicrobial efficacy comparable to NaOCl with PUI.

Summary of Research: Efficacy and Safety of the SGLT2 Inhibitor Empagliflozin Versus Placebo and the DPP-4 Inhibitor Linagliptin Versus Placebo in Young People with Type 2 Diabetes (DINAMO): A Multicentre, Randomised, Double-Blind, Parallel Group, Phase 3 Trial.

The increasing occurrence of childhood overweight and obesity has been followed by a substantial increase in youth-onset type 2 diabetes (T2D). Pharmacological treatment options for youth-onset T2D remain limited, with a clear unmet need for additional oral agents. This summary of research reports on the efficacy and safety of empagliflozin and linagliptin on glycaemic control in children and adolescents aged 10-17 years with T2D in the randomised, double-blind, parallel group, phase 3 DINAMO trial. Empagliflozin provided a clinically relevant, statistically significant, and durable improvement in glycaemic control; however, linagliptin did not. The safety profile of both empagliflozin and linagliptin was comparable to those observed in studies in adults. These results suggest that empagliflozin could be a new oral therapy option for youth-onset T2D.

SGLT2 Inhibitors - The New Standard of Care for Cardiovascular, Renal and Metabolic Protection in Type 2 Diabetes: A Narrative Review.

A substantial evidence base supports the use of sodium-glucose cotransporter-2 inhibitors (SGLT2is) in the treatment of type 2 diabetes mellitus (T2DM). This class of medicines has demonstrated important benefits that extend beyond glucose-lowering efficacy to protective mechanisms capable of slowing or preventing the onset of long-term cardiovascular, renal and metabolic (CVRM) complications, making their use highly applicable for organ protection and the maintenance of long-term health outcomes. SGLT2is have shown cost-effectiveness in T2DM management and economic savings over other glucose-lowering therapies due to reduced incidence of cardiovascular and renal events. National and international guidelines advocate SGLT2i use early in the T2DM management pathway, based upon a plethora of supporting data from large-scale cardiovascular outcome trials, renal outcomes trials and real-world studies. While most people with T2DM would benefit from CVRM protection through SGLT2i use, prescribing hesitancy remains, potentially due to confusion concerning their place in the complex therapeutic paradigm, variation in licensed indications or safety perceptions/misunderstandings associated with historical data that have since been superseded by robust clinical evidence and long-term pharmacovigilance reporting. This latest narrative review developed by the Improving Diabetes Steering Committee (IDSC) outlines the place of SGLT2is within current evidence-informed guidelines, examines their potential as the standard of care for the majority of newly diagnosed people with T2DM and sets into context the perceived risks and proven advantages of SGLT2is in terms of sustained health outcomes. The authors discuss the cost-effectiveness case for SGLT2is and provide user-friendly tools to support healthcare professionals in the correct application of these medicines in T2DM management. The previously published IDSC SGLT2i Prescribing Tool for T2DM Management has undergone updates and reformatting and is now available as a Decision Tool in an interactive pdf format as well as an abbreviated printable A4 poster/wall chart.

Association of sodium-glucose cotransporter-2 inhibitors and the risk of retinal vascular occlusion: A real-world retrospective cohort study in Taiwan.

AIMS: Sodium-glucose cotransporter-2 inhibitors (SGLT2is) are proposed to alleviate the development of inflammatory eye diseases. However, the association between SGLT2i and retinal vascular occlusion remains unclear. Therefore, this study aims to explore the effects of SGLT2i on the incidence of retinal vascular occlusion. MATERIALS AND METHODS: This retrospective cohort study analysed electronic medical records data from the largest multi-institutional database in Taiwan. Individuals who initiated SGLT2is and dipeptidyl peptidase 4 inhibitors (DPP4is) between 2016 and 2019 were included in our analysis. To conduct a homogenous comparison, inverse probability of treatment weighting with propensity scoring was employed. The primary outcome was retinal vascular occlusion, and the secondary outcomes were retinal vascular occlusion-related complications (macular oedema, vitreous haemorrhage, and tractional retinal detachment) and conditions requiring vitreoretinal intervention (intravitreal injection, retinal laser therapy, and vitrectomy). RESULTS: In total, 12,074 SGLT2i users and 39,318 DPP4i users were included. The incidence rate of retinal vascular occlusion in the SGLT2i and DPP4i groups was 1.2 (95% confidence interval [CI], 0.9-1.4) and 1.6 (95% CI, 1.3-1.8) events per 1000 person-years, respectively, which yielded a subdistribution hazard ratio (SHR) of 0.74 (95% CI, 0.55-0.99). Similar risk reductions were observed in the retinal vascular occlusion-related complications (SHR, 0.76; 95% CI, 0.69-0.84) and conditions requiring vitreoretinal intervention (SHR, 0.84; 95% CI, 0.77-0.94). CONCLUSIONS: In this multi-institutional study in Taiwan, SGLT2i use was associated with a reduced risk of retinal vascular occlusion. Further prospective studies are required to ascertain this association.

The association between sodium glucose cotransporter-2 inhibitors vs dipeptidyl peptidase-4 inhibitors and renal outcomes in people discharged from hospital with type 2 diabetes: A population-based cohort study.

BACKGROUND: We investigated the association between post-hospital discharge use of sodium glucose cotransporter-2 inhibitors (SGLT-2is) compared to dipeptidyl peptidase-4 inhibitors (DPP-4is) and the incidence of hospitalization for acute renal failure (ARF) and chronic kidney disease (CKD) in people with type 2 diabetes. METHODS: We conducted a retrospective cohort study using linked hospital and prescription data. Our cohort included people aged ≥30 years with type 2 diabetes discharged from a hospital in Victoria, Australia, from December 2013 to June 2018. We compared new users of SGLT-2is with new users of DPP-4is following discharge. People were followed from first dispensing of a SGLT-2i or DPP-4i to a subsequent hospital admission for ARF or CKD. We used competing risk models with inverse probability of treatment weighting (IPTW) to estimate subhazard ratios. RESULTS: In total, 9620 people initiated SGLT-2is and 9962 initiated DPP-4is. The incidence rate of ARF was 12.3 per 1000 person-years (median years of follow-up [interquartile range [IQR] 1.4 [0.7-2.2]) among SGLT-2i initiators and 18.9 per 1000 person-years (median years of follow-up [IQR] 1.7 [0.8-2.6]) among DPP-4i initiators (adjusted subhazard ratio with IPTW 0.78; 95% confidence interval [CI] 0.70-0.86). The incidence rate of CKD was 6.0 per 1000 person-years (median years of follow-up [IQR] 1.4 [0.7-2.2]) among SGLT-2i initiators and 8.9 per 1000 person-years (median years of follow-up [IQR] 1.7 [0.8-2.6]) among DPP-4i initiators (adjusted subhazard ratio with IPTW 0.83; 95% CI 0.73-0.94). CONCLUSIONS: Real-world data support using SGLT-2is over DPP-4is for preventing acute and chronic renal events in people with type 2 diabetes.

No change in 24-h sodium intake estimated from spot urine in Norwegian adults from 2006 to 2019: the population-based Trøndelag Health Study (HUNT).

OBJECTIVE: Monitoring time trends in salt consumption is important for evaluating the impact of salt reduction initiatives on public health outcomes. There has so far not been available data to indicate if salt consumption in Norway has changed during the previous decade. We aimed to assess whether average 24-h salt intake estimated from spot urine samples in the adult population of mid-Norway changed from 2006-2008 to 2017-2019 and to describe variations by sex, age and educational level. DESIGN: Repeated cross-sectional studies. SETTING: The population-based Trøndelag Health Study (HUNT). PARTICIPANTS: In each of two consecutive waves (HUNT3: 2006-2008 and HUNT4: 2017-2019), spot urine samples were collected from 500 men and women aged 25-64 years, in addition to 250 men and women aged 70-79 years in HUNT4. Based on spot urine concentrations of Na, K and creatinine and age, sex and BMI, we estimated 24-h Na intake using the International Cooperative Study on Salt and Blood Pressure (INTERSALT) equation for the Northern European region. RESULTS: Mean (95 % CI) estimated 24-h salt intakes in men were 11·1 (95 % CI 10·8, 11·3) g in HUNT3 and 10·9 (95 % CI 10·6, 11·1) g in HUNT4, P = 0·25. Corresponding values in women were 7·7 (95 % CI 7·5, 7·9) g and 7·7 (95 % CI 7·5, 7·9) g, P = 0·88. Mean estimated salt intake in HUNT4 decreased with increasing age in women, but not in men, and it did not differ significantly across educational level in either sex. CONCLUSIONS: Estimated 24-h salt intake in adult men and women in mid-Norway did not change from 2006-2008 to 2017-2019.

Trends and regional differences in antidiabetic medication use: a nationwide retrospective observational study.

BACKGROUND: The prevalence of diabetes is increasing, and several new drug groups have been authorized and used successfully in the treatment of diabetes, while older drug groups are still in use. Our aim was to assess the utilization tendencies and regional differences in antidiabetic medication consumption in Hungary between 2015 and 2021 and to identify the possible determinants of regional differences in antidiabetic medication use. METHODS: For this retrospective drug utilization study, yearly wholesale database was used, which provides total coverage for ambulatory antidiabetic drug sales in Hungary, including both reimbursed and non-reimbursed medications. Data were expressed as Defined Daily Dose per 1000 inhabitants per day (DDD/TID), percentage of total use and the ratio of the highest and lowest utilization values among the counties (max/min ratio). To assess the potential reasons for regional differences in antidiabetic drug use, we analyzed the associations between regional drug utilization data and possible determinants. RESULTS: The total national antidiabetic medication use has increased by 7.6% and reached 94.8 DDD/TID in 2021. Regarding antidiabetic subgroups, the use of metformin and novel antidiabetics (DPP4Is, GLP1As and SGLT2Is) and their combinations increased in all counties, while sulfonylurea consumption decreased, and insulin use was stable. In 2021, 19.2-24.1% of the total antidiabetic medication consumption was novel antidiabetics, 39.1-47.2% metformin, 14.8-25.8% sulfonylureas and 23.6-30.5% were insulins. Regional differences in antidiabetic medication consumption were considerable mainly in the case of GLP1As (max/min ratio:3.00), sulfonylureas (2.03) and SGLT2Is (1.92) in 2021. The association between antidiabetic medication use and possible determinants was confirmed in the case of unemployment rate and sulfonylurea use, the number of public medical card holders per ten thousand inhabitants and human insulin and sulfonylurea use. GLP1As were the only antidiabetic drug group that did not correlate with any of the investigated factors. CONCLUSIONS: Although novel antidiabetic drug use was growing dynamically in Hungary, sulfonylurea use is still considerable. Differences in antidiabetic drug consumption were substantial between the regions.