Hypoglycemic Drugs Research Articles

Analysing the effects of National Centralised Drug Procurement and Price Negotiation Policies on novel hypoglycaemic drug usage and costs in Shanghai, China: an interrupted time series analysis

ObjectivesTo analyse the impacts of multiple rounds of National Centralised Drug Procurement Policy (NCDP) and National Drug Price Negotiation Policy (NDPN) on the utilisation, expenditure and daily cost of novel...

Advanced AI-Driven Prediction of Pregnancy-Related Adverse Drug Reactions.

Ensuring drug safety during pregnancy is critical due to the potential risks to both the mother and fetus. However, the exclusion of pregnant women from clinical trials complicates the assessment of adverse drug reactions (ADRs) in this population. This study aimed to develop and validate risk prediction models for pregnancy-related ADRs of drugs using advanced Machine Learning (ML) and Deep Learning (DL) techniques, leveraging real-world data from the FDA Adverse Event Reporting System. We explored three methods─Information Component, Reporting Odds Ratio, and 95% confidence interval of ROR─for classifying drugs into high-risk and low-risk categories. DL models, including Directed Message Passing Neural Networks (DMPNN), Graph Neural Networks, and Graph Convolutional Networks, were developed and compared to traditional ML models like Random Forest, Support Vector Machines, and XGBoost. Among these, the DMPNN model, which integrated molecular graph information and molecular descriptors, exhibited the highest predictive performance, particularly at the preferred term level. The model was validated against external data sets from SIDER and DailyMed, demonstrating strong generalizability. Additionally, the model was applied to assess the risk of 22 oral hypoglycemic drugs, and potential substructure alerts for pregnancy-related ADRs were identified. These findings suggest that the DMPNN model is a valuable tool for predicting ADRs in pregnant women, offering significant advancement in drug safety assessment and providing crucial insights for safer medication use during pregnancy.

Synthesis and biological evaluation of esculetin derivatives as antidiabetic agents

Esculetin derivatives 4a-4j (including six novel hydroxylated/halogenated derivatives 4a, 4d, 4e, 4f, 4g, 4h) were synthesized through Perkin reaction with 2,4,5-trihydroxybenzaldehyde and appropriate phenylacetic acid as raw materials, and screened for α-glucosidase and α-amylase inhibitory activities. Among these compounds, compound 3-(3-iodophenyl)-6,7-dihydroxy-2H-chromen-2-one (4d) showed promising hypoglycaemic activity with half maximal inhibitory concentration (IC50) values of 0.18±0.03 mM and 1.82±0.18 mM against α-glucosidase and α-amylase, respectively, classifying it as a mixed-type inhibitor. Compound 4d could statically quench the intrinsic fluorescence of enzymes, which bound to enzymes mainly through hydrogen bonding and hydrophobic interactions affecting the microenvironment of proteins. Compound 4d also exhibited antioxidant activity, which demonstrated good scavenging effects for 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2, 2’-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) free radicals. Furthermore, compound 4d still maintained a certain degree of hypoglycemic and antioxidant activities after simulated gastrointestinal digestion. The oral toxicity study showed that compound 4d had no significant effect on the serum biochemical indices and organs of mice, indicating its safety profile. This study suggests that esculetin may be a potential skeleton to the development of hypoglycaemic drugs.

THE PROPER USE OF HYPOGLYCEMIC AGENTS, TYPES OF INSULIN AND TECHNOLOGICAL ADVANCES IN THE TREATMENT OF DIABETES. CASE REPORT OF A PATIENT WITH TYPE 1 DIABETES

The article entitled The Appropriate Use of Hypoglycemic Drugs, Types of Insulin and Technological Advances in the Treatment of Diabetes addresses the importance of correct management in the use of drugs and technologies to improve the treatment of diabetes. Focusing on hypoglycemic drugs and the different types of insulin, the text explores how the personalized and appropriate use of these substances helps to maintain patients' glycemic control and reduce associated complications. In addition, the article analyzes recent technological advances, such as insulin pumps and continuous glucose monitoring systems, which have made it possible to monitor glycemic rates more precisely and in real time, increasing patients' quality of life and autonomy. Together, these tools and innovations promote more effective treatment tailored to individual needs, allowing for greater safety and efficacy in diabetes management.

Androgen deprivation therapy and cardiological risks in patients with prostate cancer. Are all drugs the same?

Androgen deprivation therapy and cardiological risks in patients with prostate cancer. Are all drugs the same?

OXIDANTS AND BLOOD-RETINAL BARRIER: PROGRESSION AND MOLECULAR MECHANISMS OF DIABETIC RETINOPATHY

Diabetic retinopathy is a microvascular complication of the eye that arises as a consequence of poor control of hyperglycemia in patients with diabetes mellitus. This condition is characterized by progressive damage to the blood vessels of the retina, leading to increased vascular permeability, microaneurysms, intraretinal hemorrhages and, in more advanced stages, neovascularization. Depending on its degree of progression, it can be classified into a non-proliferative form, more frequent in the initial stages, and a proliferative form, which appears in advanced stages and is associated with a higher risk of severe visual loss. Regarding its pathophysiology, chronic hyperglycemia triggers a series of harmful metabolic and molecular pathways, such as the accumulation of reactive oxygen species, which cause oxidative stress and jointly contribute to endothelial damage and dysfunction of the blood-retinal barrier. Patients with this complication require strict and continuous glycemic control using hypoglycemic drugs capable of reducing the osmolar disturbances characteristic of diabetes, combined with specific ocular therapies such as endothelial growth factor inhibitors, which slow down neovascularization and consequently reduce the likelihood of blindness. However, even with treatment protocols, diabetic retinopathy remains the leading cause of blindness in adults worldwide, underlining the importance of prevention and early diagnosis. This study was based on the bibliographic method, collecting scientific medical data from specialized journals such as PUBMED and Scielo published between 2018 and 2023. The results highlight the close relationship between hyperglycemic states and diabetic retinopathy. Thus, it is concluded that it is essential to develop new therapies that attack not only the advanced symptoms of the disease, but also the early molecular changes that occur during the early stages of diabetic retinopathy, effectively combating the cause and effect of the pathology.

Risk of biliary diseases in patients with type 2 diabetes or obesity treated with tirzepatide: A meta-analysis.

To investigate the risk of biliary diseases in patients with type 2 diabetes mellitus (T2DM) or obesity treated with tirzepatide. Literature searches were performed using the PubMed, Web of Science, Cochrane Library, and CNKI databases until 20 May 2024. Randomized controlled studies (RCTs) investigating the safety of tirzepatide vs placebo/other hypoglycemic drugs in patients with T2DM or obesity were included. The safety outcomes mainly included the incidence of cholelithiasis, pancreatitis, cholecystitis, and gallbladder/biliary diseases. Cochrane Collaboration's tool for assessing the risk of bias was used to assess the quality of literature. Heterogeneity was evaluated using I2 statistics. A total of 12 high-quality RCTs (involving 12,351 patients) were included. The results of meta-analysis showed that tirzepatide was associated with gallbladder/biliary diseases (RR = 1.52; 95%CI: 1.17-1.98; I2 = 0%, P = 0.76) and cholelithiasis (RR = 1.67; 95%CI: 1.14-2.44; I2 = 0%, P = 0.95). Subgroup analysis based on the dose of tirzepatide found no dose-response relationship between different doses of tirzepatide and the risk of gallbladder/biliary diseases and cholelithiasis. Based on the data currently available, tirzepatide is associated with the development of cholelithiasis in patients. However, the findings from RCTs still need to be further investigated in many post-marketing safety surveillance programs.

Effects of metformin supplementation in high-carbohydrate diets on growth performance, glucose metabolism, intestinal flora, and PI3K/AKT signaling pathway of hybrid grouper (Epinephelus fuscoguttatus♀×Epinephelus lanceolatu♂)

Metformin, or 1,1-dimethylbiguanide, is a hypoglycemic drug that lowers blood glucose by reducing glycogen synthesis and increasing glucose uptake in peripheral tissues. Six diets with iso-nitrogenous and iso-lipid compositions were prepared, including a positive control (20 % carbohydrate, PC) and a negative control (30 % carbohydrate, T0). The experimental diets contained 0.2 % (T2), 0.4 % (T4), 0.6 % (T6), and 0.8 % (T8) metformin based on the negative control diet. A total of 540 hybrid groupers, with consistent size and health conditions, were randomly assigned to six groups. Each group contained 30 fish, with three replicates per group, and they were fed for eight weeks. The high-carbohydrate diet reduced weight gain, digestive enzyme activities and specific growth rates (P>0.05), while significantly increasing hepatosomatic indices (P<0.05). Metformin supplementation reduced both hepatosomatic and viscerosomatic indices (P<0.05). The high-carbohydrate diet led to increased levels of glucose, triglycerides, low-density lipoprotein, hepatic fructose 1,6-bisphosphatase, and glucose-6-phosphatase in the serum (P<0.05). In contrast, metformin supplementation significantly lowered glucose, insulin, triglycerides, and low-density lipoprotein levels (P<0.05), while enhancing the activities of hepatic glucokinase, phosphofructokinase-1, and pyruvate kinase (P<0.05). It significantly reduced the activities of PEPCK and G6Pase and downregulated the expression of ir, pi3k, pdk, ampkα1, and gs in fish on high-carbohydrate diets, while metformin supplementation upregulated the expression of ir, pi3k, pdk, ampkα1, and gs genes compared to the T0 group (P<0.05). In terms of microbiota, a high-carbohydrate diet increased pathogenic bacteria like Proteobacteria and Photobacterium, while metformin boosted beneficial bacteria such as Firmicutes and Brevibacillus. Overall, the high-carbohydrate diet impaired growth and insulin sensitivity, while metformin improved glucose metabolism, promoted beneficial bacteria, and supported intestinal health.

Time in tight range: A key metric for optimal glucose control in the era of advanced diabetes technologies and therapeutics.

Compared to glycated haemoglobin A1c (HbA1c), the rapidly developing continuous glucose monitoring (CGM) technology provides more detailed information about glycemic control. Amongst the new glucose metrics derived from CGM, time in target range of 3.9-10.0 mmol/L (time in range, TIR) has been widely used for the assessment of glucose control. In recent years, the rise of new technologies and therapies including advanced hybrid closed-loop automated insulin delivery systems and new hypoglycemic drugs has made it possible to achieve better glycemic control. In this context, the concept of time in tight range (TITR), defined as the percentage of time spent in target glucose range of 3.9-7.8 mmol/L, has gained increasing attention. Whilst TITR is highly correlated with TIR, there are still differences between the two metrics. These differences make TITR a more appropriate indicator in certain situations, such as when glucose levels are close to normal or when tighter glycemic control is required. This review summarizes recent studies related to TITR.

Enrichment, Antioxidant and Enzyme Inhibition Activities of Flavonoids from Artemisia Selengensis Turcz.

Macroporous resin was used to enrich flavonoids in the ethyl acetate extract of Artemisia Selengensis Turcz. Based on a single factor experiment, the enrichment process was optimized using the response surface method. The optimal parameters of the enrichment process were a sample concentration of 0.3 mg/mL, a loading rate of 1 mL/min, an elution flow rate of 2 mL/min, and a total flavonoid content of 155.38 ± 0.97 mg/g. The flavonoids enriched by AB-8 macroporous resin demonstrated significant scavenging activities against DPPH, ABTS+, and hydroxyl free radicals, and also exhibited certain inhibitory effects on α-amylase and α-glucosidase. Among them, the scavenging ability of the flavonoids enriched by AB-8 macroporous resin on hydroxyl free radical (IC50 = 30.31 ± 1.92 μg/mL) was the closest to Vc, and the inhibitory effect on α-glucosidase (IC50 = 16.19 ± 1.35 μg/mL) was the best. These findings confirmed the potential of Artemisia Selengensis Turcz. is a natural antioxidant and hypoglycemic drug.

Algal Active Ingredients and Their Involvement in Managing Diabetic Mellitus.

Diabetes mellitus (DM) is becoming increasingly prominent, posing a serious threat to human health. Its prevalence is rising every year, and often affects young people. In the past few decades, research on marine algae has been recognized as a major field of drug discovery. Seaweed active substances, including algal polysaccharides, algal polyphenols, algal unsaturated fatty acids, and algal dietary fiber, have unique biological activities. This article reviews the effects and mechanisms of the types, structures, and compositions of seaweed on inhibiting glucose and lipid metabolism disorders, with a focus on the inhibitory effect of active substances on blood glucose reduction. The aim is to provide a basis for the development of seaweed active substance hypoglycemic drugs.

Effects of new hypoglycemic drugs on patients with heart failure: a systematic review and network meta-analysis.

Currently, there is no relevant study comparing sodium-dependent glucose transporter 2 inhibitors (SGLT2i), glucagon-like peptide-1 receptor agonists (GLP-1RA), and dipeptidyl peptidase inhibitor (DPP4i) head to head to evaluate their comprehensive impact on heart failure patients. We conducted a comprehensive literature search across multiple databases. Utilizing the risk of bias tool from the Cochrane Collaboration, the methodological quality of included studies was critically assessed and potential publication bias was examined via funnel plots. All results are presented as mean difference; 95% confidence interval (MD; 95% CI). The network meta-analysis indicated that in regards to left ventricular function, there is a big difference in the left ventricular ejection fraction (LVEF) of Empagliflozin 25mg (13.64; 0.26, 27.01) compared to Canagliflozin 100mg; and significant differences in the left ventricular end-diastolic volume (LVEDV) and left ventricular end-systolic volume (LVESV) of Dapagliflozin 10mg (-0.76; -1.27, -0.25 and -0.95; -1.86, -0.05), Vildagliptin 50mg (-1.05; -1.47, -0.63 and -1.12; -2.19, -0.05), and Sitagliptin 100mg (-1.34; -2.31, -0.38 and -1.89; -3.50, -0.27) compared to Empagliflozin 10mg. In terms of the quality of life, there are significant differences in the N-terminal pro-B-type natriuretic peptide (NT-proBNP) and the Quality of life score of Sitagliptin 100mg (408.08; 213.59, 602.57 and 3.74; 1.57, 5.92) compared to Dapagliflozin 5mg. In terms of the cardiovascular outcome events, there is a significant difference in the heart failure rehospitalization rate of Dapagliflozin 10mg (0.45; 0.25, 0.82) and Empagliflozin 10mg (0.48; 0.28, 0.81) compared to Liraglutide 1.8mg. Further significant differences are found in the all-cause mortality of Dapagliflozin 10mg (0.81; 0.66, 0.98) compared to Vildagliptin 50mg; the cardiovascular death of Albiglutide 30mg (0.49; 0.28, 0.86) compared to Exenatide 2mg; and the arrhythmic events of Liraglutide 1.8mg (0.49; 0.26, 0.90) compared to Empagliflozin 10mg. The network meta-analysis of SGLT2i, GLP-1RA, and DPP4i as a class of drugs showed that GLP-1RA is superior to SGLT2i in improving LVEF and reducing myocardial infarction/acute coronary syndrome, whereas DPP4i is superior to SGLT2i in improving LVEDV and LVESV. GLP-1RA is superior to SGLT2i in improving LVEF and reducing myocardial infarction/acute coronary syndrome, whereas DPP4i is superior to SGLT2i in improving LVEDV and LVESV. Key message What is already known on this topic-It has been confirmed that three new hypoglycemic drugs have a protective effect on the cardiovascular system. Studies have shown that sodium-dependent glucose transporter 2 inhibitors (SGLT2i) can improve cardiovascular outcomes and enhance the quality of life of heart failure patients. Currently, SGLT2i is widely used in the clinical treatment of heart failure, and related studies have shown that glucagon-like peptide-1 receptor agonists (GLP-1RA) and dipeptidyl peptidase inhibitor (DPP4i) also play important roles in the treatment of heart failure. What this study adds-However, there is no relevant research on whether these drugs' clinical efficacy is dose-dependent. How this study might affect research, practice, or policy-This study included different doses of hypoglycemic drugs and used a network meta-analysis method to comprehensively evaluate the effects of three hypoglycemic drugs on heart function, quality of life, and prognosis in heart failure patients, providing a basis for clinical practice.

Effect of Sodium–Glucose Cotransporter 2 Inhibitors on Cardiovascular Outcomes in Patients with Acute Coronary Syndrome and Type 2 Diabetes

Effect of Sodium–Glucose Cotransporter 2 Inhibitors on Cardiovascular Outcomes in Patients with Acute Coronary Syndrome and Type 2 Diabetes

Modern aspects of therapy of metabolic associated liver disease in patients with type 2 diabetes mellitus

Metabolic associated fatty liver disease (MAFLD) is currently the most common liver disease. The main risk factors for its development are poor nutrition, sedentary lifestyle and obesity. MAFLD is associated with various cardiometabolic conditions – lipid metabolism disorders, cardiovascular pathology and carbohydrate metabolism disorders. The association of MAFLD and type 2 diabetes mellitus (DM) is common among patients, since these diseases have a common pathogenesis link – insulin resistance. The combination of these diseases has a mutual negative effect on each other and increases the risks of cardiovascular diseases, hospitalizations, as well as the risks of liver fibrosis progression. Therefore, the detection of MAFLD and its treatment in type 2 DM are extremely important to improve the patient’s prognosis. Diagnostics of MAFLD includes laboratory and instrumental research methods. The “gold standard” of diagnostics is considered to be liver biopsy, but due to the fact that this method is invasive, it is rarely used and only for differential diagnostics of MAFLD with other liver pathologies. The most accessible instrumental method for detecting liver steatosis is ultrasound. Treatment of MAFLD primarily involves lifestyle changes (rational nutrition with limitation of simple carbohydrates and animal fats, adequate physical activity) and weight loss. Also, hypoglycemic drugs used to treat type 2 diabetes (metformin, pioglitazone, glucagon-like peptide-1 agonists) can have a certain positive effect on MAFLD. Essential phospholipids, which have membrane-stabilizing, antioxidant and antifibrotic effects, are also an important component of MAFLD treatment. A number of domestic and foreign studies have shown the high efficiency of Essential Phospholipids both in relation to biochemical parameters in patients with a combination of type 2 diabetes and MAFLD, and in relation to ultrasound signs, improving the function and structure of the liver in MAFLD, as well as slowing the progression of liver fibrosis.

Relationship Between Dementia and Lifestyle Diseases

As society ages, the number of people with dementia increases worldwide, and the prevention of dementia has become increasingly important. Lifestyle diseases are associated with the development of dementia, and preventing or controlling lifestyle diseases in middle-aged individuals is particularly important. Hypertension, diabetes, and dyslipidemia are associated with dementia. Hypertension is strongly associated with dementia, and strict blood pressure control is required. Among the drugs used to treat lifestyle diseases, some antihypertensive drugs(e.g., dihydropyridine calcium channel blockers, angiotensin 2 receptor blockers), hypoglycemic drugs(e.g., glucagon-like peptide 1 receptor agonists and sodium-glucose co-transporter-2 inhibitors), and statins may reduce the incidence of dementia. However, individual interventions for lifestyle diseases have only a limited effect in reducing the incidence of dementia. Comprehensive interventions may have significant effects. Clinicians involved in the management of lifestyle diseases need to have sound knowledge of these diseases and provide comprehensive management at an early stage.

Oral administration of herbal oligonucleotide drug JGL-sRNA-h7 ameliorates hyperglycemia in db/db mice and beagle dogs.

Type 2 diabetes mellitus is a prevalent metabolic disease, posing a considerable threat to public health. Oligonucleotide drugs have proven to be a promising field of therapy for the diseases. In this study, we reported that a herbal small RNA (sRNA), JGL-sRNA-h7 (B34735529, F1439.L002444.A11), could exhibit potent hypoglycemic effects by targeting glucose-6-phosphatase. Oral administration of sphingosine (d18:1)-JGL-sRNA-h7 bencaosomes ameliorated hyperglycemia and diabetic kidney injury better than metformin in db/db mice. Furthermore, glucose tolerance was also improved in sphingosine (d18:1)-JGL-sRNA-h7 bencaosomes-treated beagle dogs. Our study indicates that JGL-sRNA-h7 could be a promising hypoglycemic oligonucleotide drug.

The Potential Impact of SGLT2-I in Diabetic Foot Prevention: Promising Pathophysiologic Implications, State of the Art, and Future Perspectives-A Narrative Review.

The impact of diabetic foot (DF) on the healthcare system represents a major public health problem, leading to a considerable clinical and economic burden. The factors contributing to DF's development and progression are strongly interconnected, including metabolic causes, neuropathy, arteriopathy, and inflammatory changes. Sodium-glucose cotransporter 2 inhibitors (SGLT2-i), novel oral hypoglycemic drugs used as an adjunct to standard treatment, have recently changed the pharmacological management of diabetes. Nevertheless, data about the risk of limb amputation, discordant and limited to canagliflozin, which is currently avoided in the case of peripheral artery disease, have potentially discouraged the design of specific studies targeting DF. There is good evidence for the single immunomodulatory, neuroprotective, and beneficial vascular effects of SGLT2-i. Still, there is no clinical evidence about the early use of SGLT2-i in diabetic foot due to the lack of longitudinal and prospective studies proving the effect of these drugs without confounders. This narrative review aims to discuss the main evidence about the impact of SGLT2-i on the three complications of diabetes implicated in the development of DF, the state of the art, and the potential future implications.

Cohort profile: the Nanjing Diabetes Cohort database – a population-based surveillance cohort

PurposeTo study epidemiology, complications, risk factors, clinical course and treatment patterns of diabetes, the Nanjing Diabetes Cohort (NDC) was established using anonymised electronic health records from 650 hospitals and primary...

Modern views on pathogenesis of cognitive impairment in patients with type 2 diabetes mellitus

Currently, the features of the pathogenesis of cognitive impairment in patients with diabetes mellitus are being actively studied. The study of the mutual influence of these pathologies is of particular relevant not only in connection with a decrease in cognitive functions in patients with diabetes mellitus, but also due to the fact that the management of diabetes mellitus requires a thorough approach to the implementation of doctor’s recommendations and self-control on the part of the patient himself. The degree of cognitive impairment has a direct impact on patient compliance and, consequently, on the management and control of the disease. A comprehensive strategy is necessary for the prevention and progression of cognitive impairments in patients with diabetes mellitus. This strategy should include minimizing modifiable risk factors, controlling comorbidities, maintaining a healthy lifestyle, following a diet, engaging in regular physical activity, and medication therapy. Also, one of the key aspects is the control of blood glucose levels. Regular monitoring and maintaining a stable level of sugar can significantly reduce the risk of developing cognitive impairments in diabetic patients. This review also analyzes the effects of oral hypoglycemic drugs, incretin-based therapy and insulin on the risk of developing cognitive impairments. This review examines important aspects of the role of pathogenetic links and clinical manifestations of type 2 diabetes mellitus in the development of cognitive impairment and the possibility of influencing their development and rate of progression. Understanding these relationships will help develop effective strategies for the prevention and treatment of cognitive impairments in patients with diabetes mellitus.

Treatment with Metformin Can Improve Insulin Resistance and Lipid Profile in Non-Diabetic Iraqi Women with Polycystic Ovary Syndrome

Abstract Background: Women with polycystic ovary syndrome (PCOS) are usually at increased risk of metabolic syndrome and insulin resistance (IR), regardless of their body weight, and the development of type 2 diabetes in those women is not uncommon. Metformin is an oral hypoglycemic drug with a significant role in improving IR and lipid profile in diabetic persons without causing hypoglycemia. Objectives: To study the effectiveness of metformin in reducing body weight, IR, and lipid profile in non-diabetic PCOS women. Materials and Methods: Two hundred women with PCOS were included in the study. Serum was taken from them, and measurement of insulin level, fasting blood sugar (FBS), glycosylated hemoglobin (HbA1c), and lipid profile were performed as a baseline. Metformin tabs of 500 mg twice daily were given for 3 months, and measurement of the previous parameters was also performed following treatment. The results were compared between pre- and post-treatment. Results: The study showed that body mass index was not changed following 3 months of metformin intake, while there was a significant reduction in FBS, serum level of insulin, HbA1c, and Homa-IR following treatment. Together and with the exception of a non-significant mild improvement in serum high-density lipoprotein level, serum levels of cholesterol, triglyceride, and low-density lipoprotein were improved with a significant reduction following metformin treatment. Conclusion: Regardless its ability to reduce body weight, metformin can be effectively used for lowering FBS, lipid profile, and improving IR in non-diabetic PCOS women and can be used as an effective intervention to improve the quality of life in women with PCOS.