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BMJ Open Diabetes Research & Care May 2024We aimed to compare the effectiveness and cost-effectiveness profiles of glucagon-like peptide-1 receptor agonist (GLP-1-RA), sodium-glucose cotransporter 2 inhibitor... (Comparative Study)
Comparative Study
INTRODUCTION
We aimed to compare the effectiveness and cost-effectiveness profiles of glucagon-like peptide-1 receptor agonist (GLP-1-RA), sodium-glucose cotransporter 2 inhibitor (SGLT2i), and dipeptidyl peptidase-4 inhibitor (DPP-4i) compared with sulfonylureas and glinides (SU).
RESEARCH DESIGN AND METHODS
Population-based retrospective cohort study based on linked regional healthcare utilization databases. The cohort included all residents in Lombardy aged ≥40 years, treated with metformin in 2014, who started a second-line treatment between 2015 and 2018 with SU, GLP-1-RA, SGLT2i, or DPP-4i. For each cohort member who started SU, one patient who began other second-line treatments was randomly selected and matched for sex, age, Multisource Comorbidity Score, and previous duration of metformin treatment. Cohort members were followed up until December 31, 2022. The association between second-line treatment and clinical outcomes was assessed using Cox proportional hazards models. The incremental cost-effectiveness ratios (ICERs) were calculated and compared between newer diabetes drugs and SU.
RESULTS
Overall, 22 867 patients with diabetes were included in the cohort, among which 10 577, 8125, 2893 and 1272 started a second-line treatment with SU, DPP-4i, SGLT2i and GLP-1-RA, respectively. Among these, 1208 patients for each group were included in the matched cohort. As compared with SU, those treated with DPP-4i, SGLT2i and GLP-1-RA were associated to a risk reduction for hospitalization for major adverse cardiovascular events (MACE) of 22% (95% CI 3% to 37%), 29% (95% CI 12% to 44%) and 41% (95% CI 26% to 53%), respectively. The ICER values indicated an average gain of €96.2 and €75.7 each month free from MACE for patients on DPP-4i and SGLT2i, respectively.
CONCLUSIONS
Newer diabetes drugs are more effective and cost-effective second-line options for the treatment of type 2 diabetes than SUs.
Topics: Humans; Diabetes Mellitus, Type 2; Male; Cost-Benefit Analysis; Female; Sulfonylurea Compounds; Retrospective Studies; Hypoglycemic Agents; Middle Aged; Aged; Dipeptidyl-Peptidase IV Inhibitors; Sodium-Glucose Transporter 2 Inhibitors; Follow-Up Studies; Treatment Outcome; Adult; Blood Glucose
PubMed: 38802266
DOI: 10.1136/bmjdrc-2023-003991 -
Revista Brasileira de Ginecologia E... 2024Potassium channels have an important role in the vascular adaptation during pregnancy and a reduction in the expression of adenosine triphosphate-sensitive potassium...
OBJECTIVE
Potassium channels have an important role in the vascular adaptation during pregnancy and a reduction in the expression of adenosine triphosphate-sensitive potassium channels (Katp) has been linked to preeclampsia. Activation of Katp induces vasodilation; however, no previous study has been conducted to evaluate the effects of the inhibition of these channels in the contractility of preeclamptic arteries. Glibenclamide is an oral antihyperglycemic agent that inhibits Katp and has been widely used in vascular studies.
METHODS
To investigate the effects of the inhibition of K, umbilical arteries of preeclamptic women and women with healthy pregnancies were assessed by vascular contractility experiments, in the presence or absence of glibenclamide. The umbilical arteries were challenged with cumulative concentrations of potassium chloride (KCl) and serotonin.
RESULTS
There were no differences between the groups concerning the maternal age and gestational age of the patients. The percentage of smokers, caucasians and primiparae per group was also similar. On the other hand, blood pressure parameters were elevated in the preeclamptic group. In addition, the preeclamptic group presented a significantly higher body mass index. The newborns of both groups presented similar APGAR scores and weights.
CONCLUSION
In the presence of glibenclamide, there was an increase in the KCl-induced contractions only in vessels from the PE group, showing a possible involvement of these channels in the disorder.
Topics: Humans; Female; Pregnancy; Pre-Eclampsia; Umbilical Arteries; Adult; Glyburide; Vasoconstriction; Young Adult; KATP Channels; Potassium Chloride
PubMed: 38765503
DOI: 10.61622/rbgo/2024AO02 -
Saudi Journal of Kidney Diseases and... Nov 2023Diabetic renal injury is a microvascular complication associated with inflammation and oxidative stress, culminating in renal dysfunction. Conventionally, it is treated...
Diabetic renal injury is a microvascular complication associated with inflammation and oxidative stress, culminating in renal dysfunction. Conventionally, it is treated with hypoglycemic agents to address metabolic perturbations. However, the way to mitigate immunological, inflammation, and oxidative stress have seldom been studied. Hence, in the present study, the nephroprotective role of immunosuppressive and anti-inflammatory drugs, mycophenolate mofetil (MMF) in combination with the oral hypoglycemic agent glibenclamide, on streptozotocin (STZ)- induced diabetic renal damage was studied. Bodyweight, fasting blood glucose, and glycosylated hemoglobin levels were altered in the diabetic rats. Furthermore, renal injury was indicated by abnormal levels of urinary protein and creatinine and serum markers of renal function in diabetic rats. Hyperglycemia-induced oxidative stress and inflammation were also observed in the diabetic rats. The combination of MMF and glibenclamide treatment significantly attenuated the abnormal effects of hyperglycemia, oxidative stress, and inflammation-induced renal injury in diabetic rats. Histopathological studies confirmed the nephroprotective role of MMF and glibenclamide by reversing renal injury in diabetic rats. The present study suggests that MMF and glibenclamide have a protective role in STZ-induced diabetic renal damage.
Topics: Animals; Glyburide; Diabetes Mellitus, Experimental; Mycophenolic Acid; Oxidative Stress; Male; Diabetic Nephropathies; Kidney; Hypoglycemic Agents; Rats, Wistar; Blood Glucose; Immunosuppressive Agents; Streptozocin; Drug Therapy, Combination; Rats; Biomarkers; Anti-Inflammatory Agents
PubMed: 38725211
DOI: 10.4103/sjkdt.sjkdt_611_20 -
Saudi Journal of Kidney Diseases and... Nov 2023Oxidative stress, imbalanced antioxidants, and dysregulated renal lipids are closely linked with diabetic nephropathy and eventual cause of end-stage renal failure. This...
Oxidative stress, imbalanced antioxidants, and dysregulated renal lipids are closely linked with diabetic nephropathy and eventual cause of end-stage renal failure. This study was performed to investigate the protective effect of bacoside-A on markers of lipid peroxidation, renal lipids, and markers of renal function in diabetic rats. Experimental diabetes was induced in Wistar rats by a single dose of streptozotocin [40 mg/kg body weight (BW)] via intraperitoneal injection. Oral administration of bacoside-A (10 mg/kg BW) and glibenclamide, a reference drug, continued for 45 days. Diabetic rats showed a significant increase in the levels of plasma glucose, renal lipids, markers of renal lipid peroxidation, and plasma biomarkers of renal function such as urea, uric acid, and creatinine. A significant decrease in the levels of plasma insulin, nonenzymatic antioxidants, and the activity of enzymatic antioxidants was seen compared with the normal controls. Bacoside-A (10 mg/kg BW) and glibenclamide (600 μg/kg BW) administered to diabetic rats resulted in a significant decrease in plasma glucose and renal lipids but a significant increase in the plasma insulin level. In addition, bacoside-A achieved a remarkable increase in the activity of enzymatic antioxidants and the levels of nonenzymatic antioxidants in the renal tissue of diabetic rats, along with significant decreases in the markers of lipid peroxidation and those of renal function, consequently substantiating the protecting effectiveness of bacoside-A in a diabetic state. These biochemical observations were supported by a histopathological study of the renal tissue. The present study suggested that bacoside-A, a triterpenoid, offers a higher renoprotective effect to counter abnormal parameters of renal function in diabetes-induced renal injury.
Topics: Animals; Oxidative Stress; Rats, Wistar; Diabetes Mellitus, Experimental; Antioxidants; Kidney; Biomarkers; Male; Lipid Peroxidation; Diabetic Nephropathies; Triterpenes; Blood Glucose; Saponins; Diabetes Mellitus, Type 2; Rats; Glyburide; Insulin; Hypoglycemic Agents
PubMed: 38725204
DOI: 10.4103/sjkdt.sjkdt_163_21 -
BMJ (Clinical Research Ed.) May 2024To compare the effectiveness of three commonly prescribed oral antidiabetic drugs added to metformin for people with type 2 diabetes mellitus requiring second line... (Comparative Study)
Comparative Study
Comparative effectiveness of second line oral antidiabetic treatments among people with type 2 diabetes mellitus: emulation of a target trial using routinely collected health data.
OBJECTIVE
To compare the effectiveness of three commonly prescribed oral antidiabetic drugs added to metformin for people with type 2 diabetes mellitus requiring second line treatment in routine clinical practice.
DESIGN
Cohort study emulating a comparative effectiveness trial (target trial).
SETTING
Linked primary care, hospital, and death data in England, 2015-21.
PARTICIPANTS
75 739 adults with type 2 diabetes mellitus who initiated second line oral antidiabetic treatment with a sulfonylurea, DPP-4 inhibitor, or SGLT-2 inhibitor added to metformin.
MAIN OUTCOME MEASURES
Primary outcome was absolute change in glycated haemoglobin A (HbA) between baseline and one year follow-up. Secondary outcomes were change in body mass index (BMI), systolic blood pressure, and estimated glomerular filtration rate (eGFR) at one year and two years, change in HbA at two years, and time to ≥40% decline in eGFR, major adverse kidney event, hospital admission for heart failure, major adverse cardiovascular event (MACE), and all cause mortality. Instrumental variable analysis was used to reduce the risk of confounding due to unobserved baseline measures.
RESULTS
75 739 people initiated second line oral antidiabetic treatment with sulfonylureas (n=25 693, 33.9%), DPP-4 inhibitors (n=34 464 ,45.5%), or SGLT-2 inhibitors (n=15 582, 20.6%). SGLT-2 inhibitors were more effective than DPP-4 inhibitors or sulfonylureas in reducing mean HbA values between baseline and one year. After the instrumental variable analysis, the mean differences in HbA change between baseline and one year were -2.5 mmol/mol (95% confidence interval (CI) -3.7 to -1.3) for SGLT-2 inhibitors versus sulfonylureas and -3.2 mmol/mol (-4.6 to -1.8) for SGLT-2 inhibitors versus DPP-4 inhibitors. SGLT-2 inhibitors were more effective than sulfonylureas or DPP-4 inhibitors in reducing BMI and systolic blood pressure. For some secondary endpoints, evidence for SGLT-2 inhibitors being more effective was lacking-the hazard ratio for MACE, for example, was 0.99 (95% CI 0.61 to 1.62) versus sulfonylureas and 0.91 (0.51 to 1.63) versus DPP-4 inhibitors. SGLT-2 inhibitors had reduced hazards of hospital admission for heart failure compared with DPP-4 inhibitors (0.32, 0.12 to 0.90) and sulfonylureas (0.46, 0.20 to 1.05). The hazard ratio for a ≥40% decline in eGFR indicated a protective effect versus sulfonylureas (0.42, 0.22 to 0.82), with high uncertainty in the estimated hazard ratio versus DPP-4 inhibitors (0.64, 0.29 to 1.43).
CONCLUSIONS
This emulation study of a target trial found that SGLT-2 inhibitors were more effective than sulfonylureas or DPP-4 inhibitors in lowering mean HbA, BMI, and systolic blood pressure and in reducing the hazards of hospital admission for heart failure ( DPP-4 inhibitors) and kidney disease progression ( sulfonylureas), with no evidence of differences in other clinical endpoints.
Topics: Humans; Diabetes Mellitus, Type 2; Hypoglycemic Agents; Male; Female; Middle Aged; Sulfonylurea Compounds; Aged; Metformin; Glycated Hemoglobin; Dipeptidyl-Peptidase IV Inhibitors; Sodium-Glucose Transporter 2 Inhibitors; Administration, Oral; Glomerular Filtration Rate; England; Drug Therapy, Combination; Treatment Outcome; Cohort Studies; Comparative Effectiveness Research; Body Mass Index; Blood Pressure
PubMed: 38719492
DOI: 10.1136/bmj-2023-077097 -
Rhode Island Medical Journal (2013) May 2024Illicit drug supply adulteration can heighten the risk for adverse health outcomes. Sulfonylurea medications are widely used in the treatment of diabetes mellitus (DM)....
Illicit drug supply adulteration can heighten the risk for adverse health outcomes. Sulfonylurea medications are widely used in the treatment of diabetes mellitus (DM). Unintentional or intentional overdose of sulfonylureas can cause refractory hypoglycemia. This case report describes a 62-year-old male patient who presented to the emergency department (ED) after being found on the ground with signs of mild trauma. He was noted to be persistently hypoglycemic despite boluses of intravenous dextrose, a dextrose infusion, and oral nutrition. The patient did report purchase and oral ingestion of pills sold as oxycodone and that the pill shape and color were different from his usual supply. The patient was empirically treated with octreotide resulting in normalization of his serum glucose. Testing demonstrated a serum glipizide concentration six times the reporting range. This case represents unintentional sulfonylurea exposure in the setting of non-prescribed oxycodone use, resulting in hypoglycemia refractory to intravenous dextrose and oral nutrition. Octreotide is an additional potential treatment for this condition. As in this case, ingestion of street drugs may present a potential source of sulfonylurea exposure. Opioid contamination with sulfonylureas has not been widely reported in the literature and knowledge about this potential exposure is important for the prompt recognition and treatment of these patients by emergency physicians.
Topics: Humans; Male; Middle Aged; Hypoglycemia; Oxycodone; Analgesics, Opioid; Drug Contamination; Hypoglycemic Agents; Sulfonylurea Compounds; Illicit Drugs; Drug Overdose; Glipizide; Octreotide
PubMed: 38687261
DOI: No ID Found -
Journal of Hazardous Materials Jun 2024Microbial herbicide degradation is an efficient bioremediation method. In this study, a strain of Streptomyces nigra, LM01, which efficiently degrades atrazine and...
Microbial herbicide degradation is an efficient bioremediation method. In this study, a strain of Streptomyces nigra, LM01, which efficiently degrades atrazine and nicosulfuron, was isolated from a corn field using a direct isolation method. The degradation effects of the identified strain on two herbicides were investigated and optimized using an artificial neural network. The maximum degradation rates of S. nigra LM01 were 58.09 % and 42.97 % for atrazine and nicosulfuron, respectively. The degradation rate of atrazine in the soil reached 67.94 % when the concentration was 10 CFU/g after 5 d and was less effective than that of nicosulfuron. Whole genome sequencing of strain LM01 helped elucidate the possible degradation pathways of atrazine and nicosulfuron. The protein sequences of strain LM01 were aligned with the sequences of the degraded proteins of the two herbicides by using the National Center for Biotechnology Information platform. The sequence (GE005358, GE001556, GE004212, GE005218, GE004846, GE002487) with the highest query cover was retained and docked with the small-molecule ligands of the herbicides. The results revealed a binding energy of - 6.23 kcal/mol between GE005358 and the atrazine ligand and - 6.66 kcal/mol between GE002487 and the nicosulfuron ligand.
Topics: Atrazine; Streptomyces; Biodegradation, Environmental; Herbicides; Sulfonylurea Compounds; Pyridines; Soil Pollutants; Genes, Bacterial; Neural Networks, Computer
PubMed: 38640665
DOI: 10.1016/j.jhazmat.2024.134336 -
BMJ Open Apr 2024To investigate the risk of cardiovascular events associated with commonly used dual and triple therapies of evogliptin, a recently introduced dipeptidyl peptidase-4...
OBJECTIVE
To investigate the risk of cardiovascular events associated with commonly used dual and triple therapies of evogliptin, a recently introduced dipeptidyl peptidase-4 inhibitor (DPP4i), for managing type 2 diabetes in routine clinical practice.
DESIGN
A retrospective cohort study.
SETTING
Korean Health Insurance Review and Assessment database.
PARTICIPANTS
Patients who initiated metformin-based dual therapy and metformin+sulfonylurea-based triple therapy in South Korea from 2014 to 2018.
INTERVENTIONS
Initiation of combination therapy with evogliptin.
PRIMARY AND SECONDARY OUTCOME MEASURES
Hazards of cardiovascular events, a composite endpoint of myocardial infarction, heart failure and cerebrovascular events, and its individual components. Cox proportional hazards model with propensity score-based inverse probability of treatment weighting were used to estimate HRs and 95% CIs.
RESULTS
From the dual and triple therapy cohorts, 5830 metformin+evogliptin users and 2198 metformin+sulfonylurea+evogliptin users were identified, respectively. Metformin+evogliptin users, as compared with metformin+non-DPP4i, had a 29% reduced risk of cardiovascular events (HR 0.71, 95% CI 0.62 to 0.82); HRs for individual outcomes were cerebrovascular events (0.71, 95% CI 0.53 to 0.95), heart failure (0.70, 95% CI 0.59 to 0.82), myocardial infarction (0.89, 95% CI 0.60 to 1.31). Metformin+sulfonylurea+evogliptin users, compared with metformin+sulfonylurea+non-DPP4i, had a 24% reduced risk of cardiovascular events (0.76, 95% CI 0.59 to 0.97); HRs for individual outcomes were myocardial infarction (0.57, 95% CI 0.27 to 1.19), heart failure (0.74, 95% CI 0.55 to 1.01), cerebrovascular events (0.96, 95% CI 0.61 to 1.51).
CONCLUSIONS
These findings suggest that dual or triple therapies of evogliptin for the management of type 2 diabetes in routine clinical practice present no cardiovascular harms, but could alternatively offer cardiovascular benefits in this patient population.
Topics: Humans; Diabetes Mellitus, Type 2; Cohort Studies; Retrospective Studies; Treatment Outcome; Hypoglycemic Agents; Metformin; Sulfonylurea Compounds; Dipeptidyl-Peptidase IV Inhibitors; Myocardial Infarction; Heart Failure; Piperazines
PubMed: 38626972
DOI: 10.1136/bmjopen-2023-077084 -
International Journal of Molecular... Apr 2024A novel organic-inorganic gliclazide-loaded composite bead was developed by an ionic gelation process using acidified CaCl, chitosan and tetraethylorthosilicate (TEOS)...
A novel organic-inorganic gliclazide-loaded composite bead was developed by an ionic gelation process using acidified CaCl, chitosan and tetraethylorthosilicate (TEOS) as a crosslinker. The beads were manufactured by crosslinking an inorganic silicone elastomer (-OH terminated polydimethylsiloxane, PDMS) with TEOS at different ratios before grafting onto an organic backbone (Na-alginate) using a 3 factorial experimental design. Gliclazide's encapsulation efficiency (EE%) and drug release over 8 h (% DR 8 h) were set as dependent responses for the optimisation of a pharmaceutical formula (herein referred to as 'G op') by response surface methodology. EE % and %DR 8 h of G op were 93.48% ± 0.19 and 70.29% ± 0.18, respectively. G op exhibited a controlled release of gliclazide that follows the Korsmeyer-Peppas kinetic model (R = 0.95) with super case II transport and pH-dependent swelling behaviour. In vitro testing of G op showed 92.17% ± 1.18 cell viability upon testing on C2C12 myoblasts, indicating the compatibility of this novel biomaterial platform with skeletal muscle drug delivery.
Topics: Gliclazide; Dimethylpolysiloxanes; Alginates; Biocompatible Materials
PubMed: 38612802
DOI: 10.3390/ijms25073991 -
Medicina (Kaunas, Lithuania) Feb 2024This review summarizes the complex relationship between medications used to treat type 2 diabetes and bone health. T2DM patients face an increased fracture risk despite... (Review)
Review
This review summarizes the complex relationship between medications used to treat type 2 diabetes and bone health. T2DM patients face an increased fracture risk despite higher bone mineral density; thus, we analyzed the impact of key drug classes, including Metformin, Sulphonylureas, SGLT-2 inhibitors, DPP-4 inhibitors, GLP-1 agonists, and Thiazolidinediones. Metformin, despite promising preclinical results, lacks a clear consensus on its role in reducing fracture risk. Sulphonylureas present conflicting data, with potential neutral effects on bone. SGLT-2 inhibitors seem to have a transient impact on serum calcium and phosphorus, but evidence on their fracture association is inconclusive. DPP-4 inhibitors emerge as promising contributors to bone health, and GLP-1 agonists exhibit positive effects on bone metabolism, reducing fracture risk. Thiazolidinediones, however, demonstrate adverse impacts on bone, inducing loss through mesenchymal stem cell effects. Insulin presents a complex relationship with bone health. While it has an anabolic effect on bone mineral density, its role in fracture risk remains inconsistent. In conclusion, a comprehensive understanding of diabetes medications' impact on bone health is crucial. Further research is needed to formulate clear guidelines for managing bone health in diabetic patients, considering individual profiles, glycemic control, and potential medication-related effects on bone.
Topics: Humans; Diabetes Mellitus, Type 2; Bone Density; Hypoglycemic Agents; Dipeptidyl-Peptidase IV Inhibitors; Sodium-Glucose Transporter 2 Inhibitors; Fractures, Bone; Metformin; Sulfonylurea Compounds; Glucagon-Like Peptide 1; Thiazolidinediones
PubMed: 38541119
DOI: 10.3390/medicina60030393