Nonglycemic Outcomes of Antidiabetic Medications.
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ABSTRACT:
SUBMITTER: Morse C
PROVIDER: S-EPMC6468830 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:ImportanceDiabetic men appear to have a lower risk of prostate cancer. Whether antidiabetic medications are protective or potentially mask prostate cancer by lowering prostate-specific antigen (PSA) levels is unclear.ObjectiveTo examine the associations of antidiabetic medication use with (1) PSA levels, (2) frequency of PSA testing, (3) receipt of biopsy following elevated PSA results, and (4) prostate cancer detection at biopsy.Design, setting, and participantsPopulation-based cohort study using data from the Stockholm PSA and Biopsy Register. Participants were all prostate cancer-free men aged 40 to 79 years residing in Stockholm County, Sweden, between January 1, 2006, and December 31, 2015. Data were analyzed from November 2018 to March 2019.ExposuresOne or more prescription for metformin, sulfonylurea, or insulin, as recorded in Sweden's National Prescribed Drug Register.Main outcomes and measuresLevels of PSA following first exposure to antidiabetic medications were assessed using multivariable linear regression. Frequency of PSA testing was assessed via multivariable Poisson regression. Biopsy following elevated PSA (≥3.0 ng/mL) and prostate cancer detection at biopsy were assessed via multivariable logistic regression.ResultsThe cohort of 564 666 men (median [range] age, 65 [40-79] years) consisted of 4583 men initially exposed to metformin, 1104 exposed to sulfonylurea, and 978 exposed to insulin who were age matched with unexposed men (1:5). Exposed men had lower median (interquartile range) PSA levels before starting antidiabetic medications compared with unexposed men (1.2 [0.7-2.5] vs 1.6 [0.8-3.2] ng/mL). After accounting for baseline differences, PSA levels did not vary from those of unexposed men following exposure to antidiabetic medications. Frequency of PSA testing was higher for those receiving metformin (rate ratio, 1.07; 95% CI, 1.06-1.09) and sulfonylurea (rate ratio, 1.06; 95% CI, 1.03-1.08) but was lower for those receiving insulin (rate ratio, 0.79; 95% CI, 0.77- 0.81). Likelihood of biopsy after elevated PSA was lower among men receiving metformin (odds ratio, 0.87; 95% CI, 0.80-0.96) and insulin (odds ratio, 0.83; 95% CI, 0.74-0.93). There were no differences in prostate cancer detection at biopsy, regardless of PSA levels that triggered the biopsy.Conclusions and relevanceThis study's findings do not support the hypothesis that the inverse association between diabetes and prostate cancer is mediated through antidiabetic medications lowering PSA levels to mask prostate cancer. They do suggest potential detection bias due to fewer biopsies among men receiving antidiabetic medications, which may explain the lower prostate cancer risk in men with diabetes.
| S-EPMC6865613 | biostudies-literature
Project description:BackgroundIt is unknown whether observational studies evaluating the association between antidiabetic medications and mortality adequately account for frailty. Our objectives were to evaluate if frailty was a potential confounder in the relationship between antidiabetic medication regimen and mortality and how well administrative and clinical electronic health record (EHR) data account for frailty.MethodsWe conducted a retrospective cohort study in a single Veterans Health Administration (VHA) healthcare system of 500 hospitalizations-the majority due to heart failure-of Veterans who received regular VHA care and initiated type 2 diabetes treatment from 2001 to 2008. We measured frailty using a modified frailty index (FI, >0.21 frail). We obtained antidiabetic medication regimen and time-to-death from administrative sources. We compared FI among patients on different antidiabetic regimens. Stepwise Cox proportional hazards regression estimated time-to-death by demographic, administrative, clinical EHR, and FI data.ResultsMedian FI was 0.22 (interquartile range 0.18, 0.27). Frailty differed across antidiabetic regimens (p < .001). An FI increase of 0.05 was associated with an increased risk of death (hazard ratio 1.45, 95% confidence interval 1.32, 1.60). Cox proportional hazards model for time-to-death including demographic, administrative, and clinical EHR data had a c-statistic of 0.70; adding FI showed marginal improvement (c-statistic 0.72).ConclusionsFrailty was associated with antidiabetic regimen and death, and may confound that relationship. Demographic, administrative, and clinical EHR data, commonly used to balance differences among exposure groups, performed moderately well in assessing risk of death, with minimal gain from adding frailty. Study design and analytic techniques can help minimize potential confounding by frailty in observational studies.
| S-EPMC6625595 | biostudies-literature
Project description:Type 2 diabetes is a debilitating disease that impacts the life expectancy, quality of life, and health of an individual. Cardiovascular disease (CVD) is a common diabetes-associated complication and a principal cause for death in diabetic patients. This review aims to investigate and summarize the effect of Type 2 diabetes mellitus (T2DM) medications on CVD issues. A comprehensive literature review mainly from level 1 evidence was performed. Thirty-seven articles were extracted from Google Scholar, ScienceDirect, ProQuest, and PubMed Database using a combination of keywords. The findings suggest that different glucose-lowering agents have been tested for their efficacy and safety in T2DM with CVD. Some of the recent trials such as the "United Kingdom Prospective Diabetes Study," "Empagliflozin (EMPA) Cardiovascular (CV) Outcome Event Trial in T2DM Patients-Removing Excess Glucose" (EMPA-REG OUTCOME), "Liraglutide Effect and Action in Diabetes: Evaluation of CV Outcome Results," and "Trial to Evaluate CV and Other Long-term Outcomes with Semaglutide in Subjects with Type 2 Diabetes" (SUSTAIN6) have shed important light on this vital clinical concern, thus demonstrating a convincing effect of liraglutide, semaglutide, and EMPA on CVD outcomes, while metformin is thought to be the first-line optimal oral agent to manage Type 2 diabetics. Some classes of drugs demonstrate CV protection, some of them may be a result of a class effect, and some differences might be based on the population enrolled individually. Most of the trials failed to show a significant benefit with regard to mortality and morbidity in spite of intensive glycemic control. This study, therefore, enabled us to develop a guide of potential antidiabetic medication that can influence or promote CV health. Health professionals in future should weigh the CV risk against possible advantages while prescribing antidiabetic medications.
| S-EPMC6124835 | biostudies-other
Project description:Objective:The objectives of this study were to estimate influenza vaccination coverage among patients with diabetes mellitus in an Italian 250 000-inhabitant area in the 2017-2018 season and to assess whether glycaemic control and pharmacological treatment were associated with the likelihood of being vaccinated. Design:In this cross-sectional study, we analysed anonymous health administrative databases, linked with each other at the individual patient level through a stochastic key: diabetes mellitus registry, vaccinations, drug prescriptions and laboratory database. Setting:The study was conducted in the catchment area of the University Hospital of Udine ('the Udine area'), a 250 000-inhabitant area in the northeast of Italy. Participants:The study included all subjects included in the regional registry of patients with diabetes mellitus, living in the Udine area as of 1 October 2017. Main outcome measures:Vaccination coverage in the 2017-2018 influenza season was calculated. The association between patients' characteristics and the likelihood of being vaccinated was assessed through multivariate log binomial regression. Result:53.0% of 15?900 patients with diabetes living in the area were vaccinated. Coverage increased with age, approaching 75% at ?85 years. Patients lacking recent glycated haemoglobin testing were less likely to be vaccinated (43.4% vaccination coverage), as were those not treated pharmacologically (44.4% vaccination coverage). Patients treated with both insulin, metformin and other antidiabetic medications were more likely to be vaccinated than those treated with metformin alone (58.1% vaccination coverage; adjusted relative risk=1.07, 95%?CI 1.01 to 1.14). Conclusion:Influenza vaccination coverage was suboptimal in this Italian population of patients with diabetes. Strategies to improve diabetes management could in turn positively affect influenza coverage.
| S-EPMC6910755 | biostudies-literature
Project description:Experimental research has shown that herbal and traditional Chinese medicines (TCM) may serve as complements to Western medicine treatments in the control of blood glucose and cardiovascular complications, but population-based studies are limited. We investigated the association between TCM use and subsequent risk of stroke in older patients with diabetes. The database used in this cohort study contained longitudinal medical claims for one million subjects randomly selected among beneficiaries of a universal health care program in Taiwan. We identified a cohort of patients with diabetes aged 65 years and older who initiated anti-diabetic medications from 2000 to 2012. Patients who had at least two TCM outpatient visits after their initiation of anti-diabetic medications were considered TCM users. The incidence of stroke was measured until 2013. Cox regression models with TCM use as a time-dependent variable were used to calculate the adjusted hazard ratios (HRs) comparing TCM use with no use. Over the 13-year period, 17,015 patients were identified; 4912 (28.9%) of them were TCM users. The incidence of stroke during the follow-up (per 1000 person-years) was 22.8 in TCM users and 25.7 in non-users. TCM users had an adjusted HR of 0.93 for the incidence of ischemic stroke (95% confidence interval [CI] 0.83, 1.04) and of 0.89 for developing hemorrhagic stroke (95% CI 0.66, 1.19), compared with non-users. In this study, in older patients receiving Western medicine treatments for diabetes, TCM use was not associated with an increased risk of developing ischemic stroke and hemorrhagic stroke.
| S-EPMC6024911 | biostudies-literature
Project description:AIMS:To compare adherence and persistence to oral antidiabetic drugs (OAD) between patients who are new users of second generation antipsychotics (SGA) versus new users of other depression therapies in adults with type 2 diabetes mellitus (T2DM) and major depressive disorder (MDD). METHODS:Adults 18-64?years with previously-treated T2DM and MDD (past OAD and SSRI/SNRI use) who are new users of SGA or non-SGA therapies (bupropion, lithium, mirtazapine, thyroid hormone, tricyclic antidepressant) were identified in the 2009-2015 MarketScan® Commercial Claims and Encounters database. Multivariate regression models were used to determine the odds of a ?10% decline in OAD adherence over 180- and 365-days, and time to OAD discontinuation, adjusting for differences between groups. RESULTS:A total of 8664 (21.5% SGA), 8311 (22.1% SGA), and 17,524 (21.3% SGA) patients met inclusion criteria for the 180-day adherence, 365-day adherence, and persistence cohorts, respectively. Over 180-days, 16.6% of SGA and 13.3% of non-SGA initiators had a ?10% decline in OAD adherence (adjusted odds ratio [OR]?=?1.41, 95% CI 1.21-1.63). Over 365-days, 22.3% of SGA and 18.9% of non-SGA initiators had a???10% decline (OR?=?1.34, 95% CI 1.17-1.53). Time to OAD discontinuation was similar between groups (adjusted hazard ratio?=?1.03, 95% CI 0.94-1.12). CONCLUSION:Use of SGA was associated with a 1.3-1.4 times higher odds of a ?10% decline in OAD adherence. Adherence to OAD is critical for optimal diabetes control and reductions in this magnitude may impact A1C. Close monitoring of OAD adherence after SGA initiation is warranted.
| S-EPMC5920707 | biostudies-literature
Project description:Precision medicine is a scientific and medical practice for personalized therapy based on patients' individual genetic, environmental, and lifestyle characteristics. Pharmacogenetics and pharmacogenomics are also rapidly developing and expanding as a key element of precision medicine, in which the association between individual genetic variabilities and drug disposition and therapeutic responses are investigated. Type 2 diabetes (T2D) is a chronic metabolic disorder characterized by hyperglycemia mainly associated with insulin resistance, with the risk of clinically important cardiovascular, neurological, and renal complications. The latest consensus report from the American Diabetes Association and European Association for the Study of Diabetes (ADA-EASD) on the management of T2D recommends preferential use of glucagon-like peptide-1 (GLP-1) receptor agonists, sodium-glucose cotransporter-2 (SGLT2) inhibitors, and some dipeptidyl peptidase-4 (DPP-4) inhibitors after initial metformin monotherapy for diabetic patients with established atherosclerotic cardiovascular or chronic kidney disease, and with risk of hypoglycemia or body weight-related problems. In this review article, we summarized current progress on pharmacogenetics of newer second-line antidiabetic medications in clinical practices and discussed their therapeutic implications for precision medicine in T2D management. Several biomarkers associated with drug responses have been identified from extensive clinical pharmacogenetic studies, and functional variations in these genes have been shown to significantly affect drug-related glycemic control, adverse reactions, and risk of diabetic complications. More comprehensive pharmacogenetic research in various clinical settings will clarify the therapeutic implications of these genes, which may be useful tools for precision medicine in the treatment and prevention of T2D and its complications.
| S-EPMC6463061 | biostudies-literature
Project description:ImportanceUnderstanding cardiovascular outcomes of initiating second-line antidiabetic medications (ADMs) may help inform treatment decisions after metformin alone is not sufficient or not tolerated. To date, no studies have compared the cardiovascular effects of all major second-line ADMs during this early decision point in the pharmacologic management of type 2 diabetes.ObjectiveTo examine the association of second-line ADM classes with major adverse cardiovascular events.Design, setting, and participantsRetrospective cohort study among 132 737 insured adults with type 2 diabetes who started therapy with a second-line ADM after taking either metformin alone or no prior ADM. This study used 2011-2015 US nationwide administrative claims data. Data analysis was performed from January 2017 to October 2018.ExposuresDipeptidyl peptidase 4 (DPP-4) inhibitors, glucagon-like peptide-1 (GLP-1) receptor agonists, sodium-glucose cotransporter 2 (SGLT-2) inhibitors, thiazolidinediones (TZDs), basal insulin, and sulfonylureas or meglitinides (both referred to as sulfonylureas hereafter). The DPP-4 inhibitors served as the comparison group in all analyses.Main outcomes and measuresThe primary outcome was time to first cardiovascular event after starting the second-line ADM. This composite outcome was based on hospitalization for the following cardiovascular conditions: congestive heart failure, stroke, ischemic heart disease, or peripheral artery disease.ResultsAmong 132 737 insured adult patients with type 2 diabetes (men, 55%; aged 45-64 years, 58%; white, 63%), there were 3480 incident cardiovascular events during 169 384 person-years of follow-up. Patients were censored after the first cardiovascular event, discontinuation of insurance coverage, transition from International Classification of Diseases, Ninth Revision (ICD-9) to end of ICD-9 coding, or 2 years of follow-up. After adjusting for patient, prescriber, and health plan characteristics, the risk of composite cardiovascular events after starting GLP-1 receptor agonists was lower than DPP-4 inhibitors (hazard ratio [HR], 0.78; 95% CI, 0.63-0.96), but this finding was not significant in all sensitivity analyses. Cardiovascular event rates after starting treatment with SGLT-2 inhibitors (HR, 0.81; 95% CI, 0.57-1.53) and TZDs (HR, 0.92; 95% CI, 0.76-1.11) were not statistically different from DPP-4 inhibitors. The comparative risk of cardiovascular events was higher after starting treatment with sulfonylureas (HR, 1.36; 95% CI, 1.23-1.49) or basal insulin (HR, 2.03; 95% CI, 1.81-2.27) than DPP-4 inhibitors.Conclusions and relevanceAmong insured adult patients with type 2 diabetes initiating second-line ADM therapy, the short-term cardiovascular outcomes of GLP-1 receptor agonists, SGLT-2 inhibitors, and DPP-4 inhibitors were similar. Higher cardiovascular risk was associated with use of sulfonylureas or basal insulin compared with newer ADM classes. Clinicians may consider prescribing GLP-1 receptor agonists, SGLT-2 inhibitors, or DPP-4 inhibitors more routinely after metformin rather than sulfonylureas or basal insulin.
| S-EPMC6324353 | biostudies-literature
Project description:BackgroundType 2 diabetes mellitus has been associated with an excess risk of colorectal cancer, although the time-risk relationship is unclear, and there is limited information on the role of antidiabetic medications.AimWe examined the association between type 2 diabetes, antidiabetic medications, and the risk of colorectal cancer, considering also duration of exposures.MethodsWe analyzed data derived from two companion case-control studies conducted in Italy and Spain between 2007 and 2013 on 1,147 histologically confirmed colorectal cancer cases and 1,594 corresponding controls. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by unconditional multiple logistic regression models, adjusted for socioeconomic factors and major potential confounding factors.ResultsOverall, 14% of cases and 12% of controls reported a diagnosis of diabetes, corresponding to an OR of colorectal cancer of 1.21 (95% CI 0.95-1.55). The OR was 1.49 (95% CI 0.97-2.29) for a duration of diabetes of at least 15?years. The OR was 1.53 (95% CI 1.06-2.19) for proximal colon cancer, 0.94 (95% CI 0.66-1.36) for distal colon cancer, and 1.32 (95% CI 0.94-1.87) for rectal cancer. In comparison with no use, metformin use was associated with a decreased colorectal cancer risk (OR 0.47, 95% CI 0.24-0.92), while insulin use was associated with an increased risk (OR 2.20, 95% CI 1.12-4.33); these associations were stronger for longer use (OR 0.36 and 8.18 for ?10?years of use of metformin and insulin, respectively).ConclusionThis study shows evidence of a positive association between diabetes and colorectal cancer, mainly proximal colon cancer. Moreover, it indicates a negative association between colorectal cancer and metformin use and a positive association for insulin use.
| S-EPMC5052265 | biostudies-literature
Project description:BackgroundType 2 diabetes mellitus has been associated with an excess risk of pancreatic cancer, but the magnitude of the risk and the time-risk relationship are unclear, and there is limited information on the role of antidiabetic medications.Patients and methodsWe analyzed individual-level data from 15 case-control studies within the Pancreatic Cancer Case-Control Consortium, including 8305 cases and 13 987 controls. Pooled odds ratios (ORs) were estimated from multiple logistic regression models, adjusted for relevant covariates.ResultsOverall, 1155 (15%) cases and 1087 (8%) controls reported a diagnosis of diabetes 2 or more years before cancer diagnosis (or interview, for controls), corresponding to an OR of 1.90 (95% confidence interval, CI, 1.72-2.09). Consistent risk estimates were observed across strata of selected covariates, including body mass index and tobacco smoking. Pancreatic cancer risk decreased with duration of diabetes, but a significant excess risk was still evident 20 or more years after diabetes diagnosis (OR 1.30, 95% CI 1.03-1.63). Among diabetics, long duration of oral antidiabetic use was associated with a decreased pancreatic cancer risk (OR 0.31, 95% CI 0.14-0.69, for ?15 years). Conversely, insulin use was associated with a pancreatic cancer risk in the short term (OR 5.60, 95% CI 3.75-8.35, for <5 years), but not for longer duration of use (OR 0.95, 95% CI 0.53-1.70, for ?15 years).ConclusionThis study provides the most definitive quantification to date of an excess risk of pancreatic cancer among diabetics. It also shows that a 30% excess risk persists for more than two decades after diabetes diagnosis, thus supporting a causal role of diabetes in pancreatic cancer. Oral antidiabetics may decrease the risk of pancreatic cancer, whereas insulin showed an inconsistent duration-risk relationship.
| S-EPMC4176453 | biostudies-literature