Users Of Glucose-lowering Drugs Research Articles

DOP57 GLP-1 based therapies and risk of Inflammatory Bowel Disease: real world evidence from a nationwide cohort study

Abstract Background Glucagon-like peptide-1 (GLP-1) based therapies, including GLP-1 receptor agonists (GLP-1RA) and dipeptidyl peptidase-4 inhibitors (DPP4i), are incretin therapies used to treat type 2 diabetes. In addition to incretin effects, GLP-1 based therapies exhibit anti-inflammatory effects. Nevertheless, a previous study reported increased risk of inflammatory bowel disease (IBD) associated with DPP4i use, while two other studies reported no altered risk. No previous studies have investigated the use of GLP-1RA and risk of IBD. In this study we investigated whether use of GLP-1 based therapies alters the risk of developing IBD among individuals with type 2 diabetes. Methods In the setting of a prospective Danish nationwide cohort study (January 1, 2007 - December 31, 2018), we applied a new user active comparator design to compare the risk of IBD in users of GLP-1 based therapies with users of other glucose-lowering drugs. Considering exposure to GLP-1 based therapies as a time-varying covariate, we used a Cox proportional hazards model adjusted for sex, age, socio-economic status, urbanisation, and metformin use to estimate hazard ratios (HRs) of IBD. Results Among 177,950 new users of glucose-lowering drugs, 412 individuals developed IBD during a median follow-up period of 4.84 (95% CI 4.82 to 4.87) years. We found no altered risk of IBD associated with the use of GLP-1 based therapies with an adjusted HR of 0.96 (95% CI 0.72 to 1.27). Adjusted HRs of IBD were 1.30 (95% CI 0.86 to 1.96) for new users of GLP-1RA and 0.84 (95% CI 0.59 to 1.19) for new users of DPP4i compared to new users of other glucose lowering drugs. Findings were consistent in all analyses, including separate analyses of Crohn’s disease and ulcerative colitis. Conclusion In a population-based cohort of individuals with type 2 diabetes, we did not find an altered risk of IBD associated with the overall use of GLP-1 based therapies. Specifically, we did not confirm the previously reported increased risk of IBD associated with DPP4i. The influence of GLP-1RA on IBD needs further examination.

Record linkage of claims and cancer registries data-Evaluation of a deterministic linkage approach based on indirect personal identifiers.

In Germany, record linkage of claims and cancer registry data is cost- and time-consuming, since up until recently no unique personal identifier was available in both data sources. The aim of this study was to evaluate the feasibility and performance of a deterministic linkage procedure based on indirect personal identifiers included in the data sources. We identified users of glucose-lowering drugs with residence in four federal states in Northern and Southern Germany (Bavaria, Bremen, Hamburg, Lower Saxony) in the German Pharmacoepidemiological Research Database (GePaRD) and assessed colorectal and thyroid cancer cases. Cancer registries of the federal states selected all colorectal and thyroid cancer cases between 2004 and 2015. A deterministic linkage approach was performed based on indirect personal identifiers such as year of birth, sex, area of residence, type of cancer and an absolute difference between the dates of cancer diagnosis in both data sources of at most 90 days. Results were compared to a probabilistic linkage using "direct" personal identifiers (gold standard). The deterministic linkage procedure yielded a sensitivity of 71.8% for colorectal cancer and 66.6% for thyroid cancer. For thyroid cancer, the sensitivity improved when using only inpatient diagnosis to define cancer in GePaRD (71.4%). Specificity was always above 99%. Using the probabilistic linkage to define cancer cases, the risk for colorectal cancer was estimated 10 percentage points lower than when using the deterministic approach. Sensitivity of the deterministic linkage approach appears to be too low to be considered as reasonable alternative to the probabilistic linkage procedure.

Mortality and other adverse outcomes in patients with type 2 diabetes mellitus admitted for COVID-19 in association with glucose-lowering drugs: a nationwide cohort study

BackgroundLimited evidence exists on the role of glucose-lowering drugs in patients with COVID-19. Our main objective was to examine the association between in-hospital death and each routine at-home glucose-lowering drug both individually and in combination with metformin in patients with type 2 diabetes mellitus admitted for COVID-19. We also evaluated their association with the composite outcome of the need for ICU admission, invasive and non-invasive mechanical ventilation, or in-hospital death as well as on the development of in-hospital complications and a long-time hospital stay.MethodsWe selected all patients with type 2 diabetes mellitus in the Spanish Society of Internal Medicine’s registry of COVID-19 patients (SEMI-COVID-19 Registry). It is an ongoing, observational, multicenter, nationwide cohort of patients admitted for COVID-19 in Spain from March 1, 2020. Each glucose-lowering drug user was matched with a user of other glucose-lowering drugs in a 1:1 manner by propensity scores. In order to assess the adequacy of propensity score matching, we used the standardized mean difference found in patient characteristics after matching. There was considered to be a significant imbalance in the group if a standardized mean difference > 10% was found. To evaluate the association between treatment and study outcomes, both conditional logit and mixed effect logistic regressions were used when the sample size was ≥ 100.ResultsA total of 2666 patients were found in the SEMI-COVID-19 Registry, 1297 on glucose-lowering drugs in monotherapy and 465 in combination with metformin. After propensity matching, 249 patients on metformin, 105 on dipeptidyl peptidase-4 inhibitors, 129 on insulin, 127 on metformin/dipeptidyl peptidase-4 inhibitors, 34 on metformin/sodium-glucose cotransporter 2 inhibitor, and 67 on metformin/insulin were selected. No at-home glucose-lowering drugs showed a significant association with in-hospital death; the composite outcome of the need of intensive care unit admission, mechanical ventilation, or in-hospital death; in-hospital complications; or long-time hospital stays.ConclusionsIn patients with type 2 diabetes mellitus admitted for COVID-19, at-home glucose-lowering drugs showed no significant association with mortality and adverse outcomes. Given the close relationship between diabetes and COVID-19 and the limited evidence on the role of glucose-lowering drugs, prospective studies are needed.

Intensive monitoring of adverse drug events associated with the use of new glucose‐lowering drugs: results from an inception cohort study in Portugal

To determine the frequency and the time-course profile of adverse drug events associated with new glucose-lowering drugs in daily practice and to explore factors potentially associated to these events. An inception cohort study was implemented. Adults with type 2 diabetes mellitus initiating a dipeptidyl peptidase-4 inhibitor, a glucagon-like peptide-1 receptor agonist or a sodium-glucose co-transporter-2 inhibitor were eligible for inclusion. Data were collected through baseline and follow-up telephone questionnaires, administered at 2 weeks, 3 months and 6 months. Kaplan-Meier curves and log-rank were computed to compare the time to adverse drug event onset. Cox models were used to explore potential factors associated with adverse drug events. A total of 1328 participants were recruited to the study. In all, 1118 adverse drug events were reported (of which 36% were not listed in the summary of product characteristics) by 41% of participants. The median latency time of adverse drug events reported in ≥1% of participants ranged from 0 to 2 days. Glucagon-like peptide-1 receptor agonist and sodium-glucose co-transporter-2 inhibitor subgroups were associated with an increased likelihood of adverse drug event reporting when compared with the dipeptidyl peptidase-4 inhibitor subgroup. A total of 328 glucose-lowering drugs were withdrawn, more than half as a result of an adverse drug event. More than two-fifths of participants reported an adverse drug event; dipeptidyl peptidase-4 inhibitors led to the highest proportion of unlabelled adverse drug events. Adverse drug event latency time data show that counselling and adverse drug event management should be proactively addressed from treatment initiation. There should be greater focus on prevalent new users of glucose-lowering drugs, who were more complex participants in this study in terms of type 2 diabetes disease, as they were more likely to report an adverse drug event than the incident new users.

Glucose-Lowering Drugs Linked to Increased Fracture Risk in Patients With Diabetes

Researchers in Denmark have concluded that use of glucose-lowering sulfonylureas and glitazones within 90 days increased the risk for hip fractures in elderly patients with type 2 diabetes. Current use of sulfonylureas was also associated with an increased risk of other fractures including vertebral and forearm. “Current use of sulfonylureas and glitazones was associated with increased risk of a hip fracture, and the risk remained increased after adjustment for comorbidities and previous admissions due to falls and hypoglycemic events,” the researchers concluded (Bone 2017:95;136–42). “By contrast, hip fracture risk was not increased in ever users of glucose-lowering drugs among patients with incident type 2 diabetes.” Previous research has shown that patients with type 2 diabetes are at 1.4-fold increased risk for hip fracture, but there are conflicting data on the effect of sulfonylureas. Researchers led by Jakob Starup-Linde, PhD, selected 5244 patients from a cohort of diabetes patients (n = 501,724) entered into the Danish National Patient Register and the Register of Medicinal Product Statistics from January 1996 to December 2011. Patients with type 1 diabetes were excluded. Researchers followed the cohort from the time of diabetes diagnosis to time of fracture or date of death, emigration, or end of study. Mean follow-up was 5.5 years for patients with a hip fracture and 6.4 years for patients who did not have a fracture. Mean follow-up was 5.2 years for patients with a fracture at a major osteoporotic site, 5 years for any fracture, 5.2 years for vertebral fractures, and 5.2 years for forearm fractures. Compared with non-diabetic patients, major osteoporotic fractures and any fractures were more common than hip fractures in patients with type 2 diabetes. Patients who suffered a hip fracture were significantly older than those without a hip fracture, and women with type 2 diabetes were at greater risk for hip fracture than men. “The most plausible reason for an increased risk of fracture within sulfonylurea users are hypoglycemic events,” Dr. Starup-Linde, from the department of endocrinology and internal medicine, Aarhus University Hospital, Denmark, told Caring. “Sulfonylureas are known to cause hypoglycemia by increasing beta cell insulin release. Hypoglycemia may lead to falls and thereby fractures.” Previous and current use of sulfonylureas were associated with an increased risk for hip fracture in the unadjusted model (HR, 1.08). Current use of sulfonylureas increased the risk for hip fracture in all models. However, ever use of sulfonylurea use was associated with a lower fracture risk in the adjusted (HR, 0.81) and propensity adjusted (HR, 0.91) models. Ever use of glitazones was associated with a higher risk of a hip fracture in the unadjusted model (HR, 0.28) but the effect was neutral in the adjusted models. Current use of glitazones was associated with a lower risk of hip fracture in the unadjusted model, but researchers said glitazones were a strong risk factor for fracture in the 90-day propensity adjusted models (HR, 2.07). When researchers examined the effect of new use of a glucose-lowering drug, sulfonylureas (HR, 1.91) and glitazones (HR, 7.18) were associated with an increased risk for hip fracture. Current use of sulfonylureas was associated with an increased risk for any fracture (HR, 1.44), major osteoporotic fracture (HR, 1.54), vertebral fracture (HR, 1.47; 95% CI, 1.24–1.74), and forearm fracture (HR, 1.55). Current use of glitazones was associated with an increased risk for any fracture (HR, 3.01), major osteoporotic fracture (HR, 3.71), vertebral fracture (HR, 4.53), and forearm fracture (HR, 4.89). In contrast, current use of metformin, dipeptidyl peptidase IV-inhibitors, or peptide-1 receptor agonists was associated with reduced risk for decreased risk of any fracture, major osteoporotic fracture, vertebral fracture, and forearm fracture. “To the best of our knowledge, this is the largest study on incident hip and osteoporotic fractures among incident cases of type 2 diabetes,” the researchers wrote. “The present investigation is limited by the lack of information on bone mass, body mass index, lifestyle habits as smoking and daily alcohol consumption, vitamin D status, and other biochemical parameters. These factors are important to consider when interpreting the risk of fracture.” Jason Harris is a freelance medical writer based in Philadelphia.

Impact of cancer diagnosis and treatment on glycaemic control among individuals with colorectal cancer using glucose-lowering drugs.

This study aims to evaluate the impact of cancer and its treatment on HbA1c values among individuals with colorectal cancer (CRC) using glucose-lowering drugs (GLDs). Patients with primary CRC (1998-2011) were selected from the Eindhoven Cancer Registry and linked to the PHARMO Database Network including outpatient pharmacy and clinical laboratory data. Patients with more than 2years of GLDs use prior to cancer diagnosis were included. Linear mixed-effects models were conducted to evaluate changes in HbA1c for colon cancer (CC) and rectal cancer (RC) patients in the 4years around CRC diagnosis. Of all CRC patients (n=4714), 294 (6%) GLDs users with CC and 144 (3%) with RC were selected. In the crude model, mean HbA1c at cancer diagnosis was 6.9% (51.6mmol/mol) among CC patients and 7.1% (53.5mmol/mol) among RC patients. Among CC patients, HbA1c decreased with 0.12% per year (p=0.0002) before cancer diagnosis in the adjusted model, and after diagnosis, it increased with 0.12% per year (p=0.02). In subgroup analyses, effects on HbA1c were more pronounced in users of anti-anaemic preparations. Among RC patients, HbA1c decreased before diagnosis with 0.18% per year (p=0.0006), whereas after diagnosis it changed non-significantly. Among users of GLDs, HbA1c decreased with 0.12-0.18% (1-2mmol/mol) per year before CRC diagnosis. Only among CC patients, HbA1c increased after diagnosis (0.12% per year; 1.3mmol/mol). Modest changes in HbA1c before CRC diagnosis may reflect the effects of an undiagnosed cancer, such as weight loss, anaemia, or the use of anti-anaemic preparations.