Investigation of Concomitant Use of Alzheimer's Disease Drugs with Sulfonylureas and Serious Hypoglycemia.
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ABSTRACT:
SUBMITTER: Nam YH
PROVIDER: S-EPMC7708459 | biostudies-literature | 2021 Jan
REPOSITORIES: biostudies-literature
Publications
Investigation of Concomitant Use of Alzheimer's Disease Drugs with Sulfonylureas and Serious Hypoglycemia.
Nam Young Hee YH Brensinger Colleen M CM Bilker Warren B WB Leonard Charles E CE Hennessy Sean S
Epidemiology (Cambridge, Mass.) 20210101 1
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Project description:Prior research suggests that warfarin, when given concomitantly with some sulfonylureas, may increase the risk of serious hypoglycemia. However, the clinical significance remains unclear. We examined rate ratios (RRs) for the association between serious hypoglycemia and concomitant use of warfarin with either sulfonylureas or metformin using a self-controlled case series design and US Medicaid claims (supplemented with Medicare claims) from 1999 to 2011. Across all risk windows combined, warfarin was associated with an elevated rate of serious hypoglycemia when given concomitantly with glimepiride (RR, 1.47; 95% confidence interval (CI), 1.07-2.02) and metformin (RR, 1.73; 95% CI, 1.38-2.16). Particularly in the late risk window (>120 days since beginning concomitancy), most of the RRs for warfarin were elevated: glipizide (RR, 1.72; 95% CI, 1.29-2.29), glyburide (RR, 1.57; 95% CI, 1.15-2.15), metformin (RR, 2.26; 95% CI, 1.67-3.05), and glimepiride (RR, 1.56; 95% CI, 0.97-2.50). These results are consistent with a previously hypothesized hypoglycemic effect of warfarin in patients with type 2 diabetes through inhibition of the carboxylation of osteocalcin.
| S-EPMC6754096 | biostudies-literature
Project description:BackgroundIn a previous drug-drug interaction (DDI) screening study intended to generate hypotheses, clopidogrel + either eszopiclone or zolpidem (vs. clopidogrel alone) were associated with serious bleeding.ObjectivesTo confirm or refute these DDI signals and examine associations with other hypnotics in an independent population of United States Medicaid beneficiaries METHODS: We employed a bi-directional self-controlled case series design in eligible individuals concomitantly exposed to one of 12 hypnotics (precipitants, exposures of interest) plus either clopidogrel (the object drug) or pravastatin (the negative control object drug). The outcome was hospital presentation with serious bleeding. Using conditional Poisson regression, we calculated confounder-adjusted rate ratios (RRs) and 95% confidence intervals for serious bleeding during clopidogrel + precipitant use (vs. clopidogrel alone). To distinguish a DDI from a precipitant's inherent effect on bleeding, we divided effect measures by the adjusted RR for the corresponding pravastatin + precipitant pair to obtain ratios of RR (RRRs).ResultsAmong 23,194 users of clopidogrel and 3824 of pravastatin who experienced serious bleeding during an active prescription for one of these agents, confounder-adjusted RRRs for serious bleeding were 6.63 (0.39-113.01) and 0.77 (0.53-1.11) with eszopiclone and zolpidem, respectively, whereas confounder-adjusted RRRs for other hypnotics ranged from 0.18 (0.04-0.85) for triazolam to 1.79 (0.16-20.44) for zaleplon. Statistical imprecision therefore precluded us from confirming or refuting these prior signals with eszopiclone and zolpidem.ConclusionsWhile we could not confirm or refute previously identified DDI signals, numerically elevated RRRs for serious bleeding with several clopidogrel + hypnotic pairs warrant further examination.
| S-EPMC8187300 | biostudies-literature
Project description:Study questionIs warfarin use associated with an increased risk of serious hypoglycemic events among older people treated with the sulfonylureas glipizide and glimepiride?MethodsThis was a retrospective cohort analysis of pharmacy and medical claims from a 20% random sample of Medicare fee for service beneficiaries aged 65 years or older. It included 465,918 beneficiaries with diabetes who filled a prescription for glipizide or glimepiride between 2006 and 2011 (4,355,418 person quarters); 71,895 (15.4%) patients also filled a prescription for warfarin (416,479 person quarters with warfarin use). The main outcome measure was emergency department visit or hospital admission with a primary diagnosis of hypoglycemia in person quarters with concurrent fills of warfarin and glipizide/glimepiride compared with the rates in quarters with glipizide/glimepiride fills only, Multivariable logistic regression was used to adjust for individual characteristics. Secondary outcomes included fall related fracture and altered consciousness/mental status.Summary answer and limitationsIn quarters with glipizide/glimepiride use, hospital admissions or emergency department visits for hypoglycemia were more common in person quarters with concurrent warfarin use compared with quarters without warfarin use (294/416,479 v 1903/3,938,939; adjusted odds ratio 1.22, 95% confidence interval 1.05 to 1.42). The risk of hypoglycemia associated with concurrent use was higher among people using warfarin for the first time, as well as in those aged 65-74 years. Concurrent use of warfarin and glipizide/glimepiride was also associated with hospital admission or emergency department visit for fall related fractures (3919/416,479 v 20,759/3,938,939; adjusted odds ratio 1.47, 1.41 to 1.54) and altered consciousness/mental status (2490/416,479 v 14,414/3,938,939; adjusted odds ratio 1.22, 1.16 to 1.29). Unmeasured factors could be correlated with both warfarin use and serious hypoglycemic events, leading to confounding. The findings may not generalize beyond the elderly Medicare population.What this study addsA substantial positive association was seen between use of warfarin with glipizide/glimepiride and hospital admission/emergency department visits for hypoglycemia and related diagnoses, particularly in patients starting warfarin. The findings suggest the possibility of a significant drug interaction between these medications.Funding, competing interests, data sharingJAR and DPG receive support from the National Institute on Aging, the Commonwealth Fund, and the Leonard D. Schaeffer Center for Health Policy and Economics at the University of Southern California. ABJ receives support from the NIH Office of the Director. No additional data are available.
| S-EPMC4670968 | biostudies-literature
Project description:ImportanceCertain antimicrobial drugs interact with sulfonylureas to increase the risk of hypoglycemia.ObjectiveTo determine the risk of hypoglycemia and associated costs in older patients prescribed glipizide or glyburide who fill a prescription for an antimicrobial drug.Design, setting, and participantsThis was a retrospective cohort study of Texas Medicare claims from 2006 to 2009 for patients 66 years or older who were prescribed glipizide or glyburide and who also filled a prescription for 1 of the 16 antimicrobials most commonly prescribed for this population.MethodsWe assessed hypoglycemia events and associated Medicare costs in patients prescribed 1 of 7 antimicrobial agents thought to interact with sulfonylureas, using noninteracting antimicrobials as a comparison. We used a repeated measure logistic regression, controlling for age, sex, ethnicity, Medicaid eligibility, comorbidity, prior emergency department visits for hypoglycemia, prior hospitalizations for any cause, nursing home residence, and indication for the antimicrobial. We estimated odds of hypoglycemia, number needed to harm, deaths during hospitalization for hypoglycemia, and Medicare costs for hypoglycemia treatment.Main outcomes and measuresAny hospitalization or emergency department visit owing to hypoglycemia within 14 days of antimicrobial exposure.ResultsIn multivariable analyses controlling for patient characteristics and indication for antimicrobial drug use, clarithromycin (odds ratio [OR], 3.96 [95% CI, 2.42-6.49]), levofloxacin (OR, 2.60 [95% CI, 2.18-3.10]), sulfamethoxazole-trimethoprim (OR, 2.56 [95% CI, 2.12-3.10]), metronidazole (OR, 2.11 [95% CI, 1.28-3.47]), and ciprofloxacin (OR, 1.62 [95% CI, 1.33-1.97]) were associated with higher rates of hypoglycemia compared with a panel of noninteracting antimicrobials. The number needed to harm ranged from 71 for clarithromycin to 334 for ciprofloxacin. Patient factors associated with hypoglycemia included older age, female sex, black or Hispanic race/ethnicity, higher comorbidity, and prior hypoglycemic episode. In 2009, 28.3% of patients prescribed a sulfonylurea filled a prescription for 1 of these 5 antimicrobials, which were associated with 13.2% of all hypoglycemia events in patients taking sulfonylureas. The treatment of subsequent hypoglycemia adds $30.54 in additional Medicare costs to each prescription of 1 of those 5 antimicrobials given to patients taking sulfonylureas.Conclusions and relevancePrescription of interacting antimicrobial drugs to patients on sulfonylureas is very common, and is associated with substantial morbidity and increased costs.
| S-EPMC4878670 | biostudies-literature
Project description:The aggregation and accumulation of amyloid-? plaques and tau proteins in the brain have been central characteristics in the pathophysiology of Alzheimer's disease (AD), making them the focus of most of the research exploring potential therapeutics for this neurodegenerative disease. With success in interventions aimed at depleting amyloid-? peptides being limited at best, a greater understanding of the physiological role of amyloid-? peptides is needed. The development of amyloid-? plaques has been determined to occur 10-20 years prior to AD symptom manifestation, hence earlier interventions might be necessary to address presymptomatic AD. Furthermore, recent studies have suggested that amyloid-? peptides may play a role in innate immunity as an antimicrobial peptide. These findings, coupled with the evidence of pathogens such as viruses and bacteria in AD brains, suggests that the buildup of amyloid-? plaques could be a response to the presence of viruses and bacteria. This has led to the foundation of the antimicrobial hypothesis for AD. The present review will highlight the current understanding of amyloid-?, and the role of bacteria and viruses in AD, and will also explore the therapeutic potential of antimicrobial and antiviral drugs in Alzheimer's disease.
| S-EPMC7404195 | biostudies-literature
Project description:Alzheimer's disease (AD) is an age-dependent neurodegenerative disorder and the most common cause of dementia. The early stages of AD are characterized by short-term memory loss. Once the disease progresses, patients experience difficulties in sense of direction, oral communication, calculation, ability to learn, and cognitive thinking. The median duration of the disease is 10 years. The pathology is characterized by deposition of amyloid beta peptide (so-called senile plaques) and tau protein in the form of neurofibrillary tangles. Currently, two classes of drugs are licensed by the European Medicines Agency for the treatment of AD, ie, acetylcholinesterase inhibitors for mild to moderate AD, and memantine, an N-methyl-D-aspartate receptor antagonist, for moderate and severe AD. Treatment with acetylcholinesterase inhibitors or memantine aims at slowing progression and controlling symptoms, whereas drugs under development are intended to modify the pathologic steps leading to AD. Herein, we review the clinical features, pharmacologic properties, and cost-effectiveness of the available acetylcholinesterase inhibitors and memantine, and focus on disease-modifying drugs aiming to interfere with the amyloid beta peptide, including vaccination, passive immunization, and tau deposition.
| S-EPMC3862506 | biostudies-other
Project description:According to the World Alzheimer's report, dementia was estimated to affect 50 million worldwide in 2018, number expected to increase to more than 150 million within 30 years. Alzheimer's disease is the most common type of dementia, accounting on its own for 2/3 of all dementia cases. The initial signs and symptoms of Alzheimer's disease relate to progressive cognitive decline, inexorably progressing until the loss of independence. Neuropsychiatric and behavioral symptoms may occur during the progression of the disease; around 20% of patients without any behavioral symptoms at the diagnosis will experience some of them within 2 years. Consequences are early institutionalization, lower quality of life, of both patients and carers, and more severe cognitive impairment. Treatment options for behavioral symptoms include pharmacological and non-pharmacological approaches. The latter are usually preferred, since antipsychotic therapy is not free from several, and often serious, adverse events. However, behavioral symptoms are not always controllable with non-pharmacological intervention. The psychotropic class of medication more frequently prescribed for behavioral symptoms are atypical antipsychotics; among them, risperidone is the only one licensed for the treatment of aggression, in Europe but not in the USA. On that regard, the use of antipsychotic drugs should be limited, due to the increased risk of mortality, stroke, hallucination, and higher risk of relapse after discontinuation. Some new agents are under evaluation, such as pimavanserin and lumateperone. In this review, we are evaluating the current available pharmacological options to treat behavioral symptoms as well as the forthcoming new agents.
| S-EPMC6915160 | biostudies-literature
Project description:We provide an overview of rehabilitation in neurological diseases. A large amount of literature available on neurorehabilitation is based from the rehabilitative work on stroke and spinal cord injuries. After a brief description of rehabilitation, the potential application of neurorehabilitation in neurodegenerative diseases specifically multiple sclerosis (MS) is summarized. Since MS causes a wide variety of symptoms, the rehabilitation in MS patients may benefit from an interdisciplinary approach that encloses physiotherapy, cognitive rehabilitation, psychological therapy, occupational therapy, and other methods to improve fatigue. Neurorehabilitation helps patients to reach and maintain their optimal physical, psychological and intellectual, levels but it does not reverse long-term disabilities that arise from neurological disorders. This calls for the need of better neuroregenerative and neuroprotective treatment strategies in addition to neurorehabilitation. We discuss neuroprotective drugs aimed at preventing axonal, neuronal, myelin and oligodendrocyte damage and cell death that are approved and others that are currently in clinical trials, with an emphasis on human derived natural antibodies with remyleination potential. Our investigative group developed recombinant natural human IgM antibodies against oligodendrocytes and neurons with a potential for CNS repair and remyleination. One such recombinant antibody, rHIgM22 completed a phase 1 clinical trial with no toxicity and with an objective of promoting remyleination in multiple sclerosis. Inclusion of these drugs as a multifaceted approach may further enhance the efficacy of neurorehabilitation in neuroinflammatory and neurodegenerative disorders.
| S-EPMC5006625 | biostudies-literature
Project description:In a prior screening study, saxagliptin, a dipeptidyl peptidase-4 inhibitor (DPP-4i), was found to have an increased rate of serious bleeding when used concomitantly with several oral anticoagulants (OACs). We aimed to confirm or refute the associations between concomitant use of individual OACs and DPP-4is and serious bleeding in a large US database, using self-controlled case series (SCCS) and case-crossover (CCO) designs. The study population was eligible Medicare beneficiaries co-exposed to a DPP-4i (precipitant) and either an OAC (object drug) or lisinopril (negative control object drug) in 2016-2020. For the SCCS, we used conditional Poisson regression to estimate adjusted rate ratios (RRs) between each co-exposure (vs. not) and serious bleeding and divided the RR by the adjusted RR for the corresponding lisinopril + precipitant pair to obtain ratios of RRs (RRRs). For the CCO, we estimated the adjusted odds ratios (ORs) of exposure to the precipitant in the focal window vs. referent window using multivariable conditional logistic regression and divided the ORs in the object drug-exposed cases over the ORs in negative object drug-exposed cases to obtain the ratios of ORs (RORs). The adjusted RRRs for serious bleeding ranged from 0.32 (0.05-1.91) for apixaban/lisinopril + saxagliptin to 3.49 (1.29-9.48) for warfarin/lisinopril + linagliptin. The adjusted RORs ranged from 0.01 (0.00-0.20) for rivaroxaban/lisinopril + saxagliptin to 2.99 (0.74-12.11) for apixaban/lisinopril + linagliptin. While we could not confirm previously identified signals because of statistical imprecision, several numerically elevated estimates still warrant caution in concomitant use and further examination.
| S-EPMC11893511 | biostudies-literature
Project description:ObjectiveTo investigate the association of concurrent use of oral anticoagulants (OACs) and sulfonylureas and the risk of hypoglycemia in individuals with type 2 diabetes mellitus (T2DM).Research design and methodsA retrospective cohort study was conducted between 2001 and 2017 using electronic primary healthcare data from the IQVIA Medical Research Data (IMRD) that incorporates data supplied by The Health Improvement Network (THIN), a propriety database of Cegedim SA. Individuals with T2DM who received OAC prescription and sulfonylureas were included. We compared the risk of hypoglycemia with sulfonylureas and OACs using propensity score matching and Cox regression.Results109,040 individuals using warfarin and sulfonylureas and 77,296 using direct oral anticoagulants (DOACs) and sulfonylureas were identified and included. There were 285 hypoglycemia events in the warfarin with sulfonylureas group (incidence rate = 17.8 per 1,000 person-years), while in the sulfonylureas only, 304 hypoglycemia events were observed (incidence rate = 14.4 per 1,000 person-years). There were 14 hypoglycemic events in the DOACs with sulfonylureas group (incidence rates = 14.8 per 1,000 person-years), while in the sulfonylureas alone group, 60 hypoglycemia events were observed (incidence rate =23.7 per 1,000 person-years). Concurrent use of warfarin and sulfonylureas was associated with increased risk of hypoglycemia compared with sulfonylureas alone (HR 1.38; 95% CI 1.10-1.75). However, we found no evidence of an association between concurrent use of DOACs and sulfonylureas and risk of hypoglycemia (HR 0.54; 95% CI, 0.27-1.10) when compared with sulfonylureas only.ConclusionsWe provide real-world evidence of possible drug-drug interactions between warfarin and sulfonylureas. The decision to prescribe warfarin with coexistent sulfonylureas to individuals with T2DM should be carefully evaluated in the context of other risk factors of hypoglycemia, and availability of alternative medications.
| S-EPMC9445245 | biostudies-literature