Limited medication adherence and persistence with treatment are barriers to successful management of type 2 diabetes (T2D). We searched MEDLINE, EMBASE, the Cochrane Library, the Register of ...Controlled Trials, PsychINFO and CINAHL for observational and interventional studies that compared the adherence or persistence associated with 2 or more glucose‐lowering medications in people with T2D. Where 5 or more studies provided the same comparison, a random‐effects meta‐analysis was performed, reporting mean difference (MD) or odds ratio (OR) for adherence or persistence, depending on the pooled study outcomes. We included a total of 48 studies. Compared with metformin, adherence (%) was better for sulphonylureas (5 studies; MD 10.6%, 95% confidence interval CI 6.5‐14.7) and thiazolidinediones (TZDs; 6 studies; MD 11.3%, 95% CI 2.7%‐20.0%). Adherence to TZDs was marginally better than adherence to sulphonylureas (5 studies; MD 1.5%, 95% CI 0.1‐2.9). Dipeptidyl peptidase‐4 inhibitors had better adherence than sulphonylureas and TZDs. Glucagon‐like peptide‐1 receptor agonists had higher rates of discontinuation than long‐acting analogue insulins (6 studies; OR 1.95; 95% CI 1.17‐3.27). Long‐acting insulin analogues had better persistence than human insulins (5 studies; MD 43.1 days; 95% CI 22.0‐64.2). The methods used to define adherence and persistence were highly variable.
PurposeThe Royal College of General Practitioners Research and Surveillance Centre (RCGP RSC) is one of the longest established primary care sentinel networks. In 2015, it established a new data and ...analysis hub at the University of Surrey. This paper evaluates the representativeness of the RCGP RSC network against the English population.Participants and methodThe cohort includes 1 042 063 patients registered in 107 participating general practitioner (GP) practices. We compared the RCGP RSC data with English national data in the following areas: demographics; geographical distribution; chronic disease prevalence, management and completeness of data recording; and prescribing and vaccine uptake. We also assessed practices within the network participating in a national swabbing programme.Findings to dateWe found a small over-representation of people in the 25–44 age band, under-representation of white ethnicity, and of less deprived people. Geographical focus is in London, with less practices in the southwest and east of England. We found differences in the prevalence of diabetes (national: 6.4%, RCPG RSC: 5.8%), learning disabilities (national: 0.44%, RCPG RSC: 0.40%), obesity (national: 9.2%, RCPG RSC: 8.0%), pulmonary disease (national: 1.8%, RCPG RSC: 1.6%), and cardiovascular diseases (national: 1.1%, RCPG RSC: 1.2%). Data completeness in risk factors for diabetic population is high (77–99%). We found differences in prescribing rates and costs for infections (national: 5.58%, RCPG RSC: 7.12%), and for nutrition and blood conditions (national: 6.26%, RCPG RSC: 4.50%). Differences in vaccine uptake were seen in patients aged 2 years (national: 38.5%, RCPG RSC: 32.8%). Owing to large numbers, most differences were significant (p<0.00015).Future plansThe RCGP RSC is a representative network, having only small differences with the national population, which have now been quantified and can be assessed for clinical relevance for specific studies. This network is a rich source for research into routine practice.
Disparities in type 2 diabetes (T2D) care provision and clinical outcomes have been reported in the last 2 decades in the UK. Since then, a number of initiatives have attempted to address this ...imbalance. The aim was to evaluate contemporary data as to whether disparities exist in glycaemic control, monitoring, and prescribing in people with T2D.
A T2D cohort was identified from the Royal College of General Practitioners Research and Surveillance Centre dataset: a nationally representative sample of 164 primary care practices (general practices) across England. Diabetes healthcare provision and glucose-lowering medication use between 1 January 2012 and 31 December 2016 were studied. Healthcare provision included annual HbA1c, renal function (estimated glomerular filtration rate eGFR), blood pressure (BP), retinopathy, and neuropathy testing. Variables potentially associated with disparity outcomes were assessed using mixed effects logistic and linear regression, adjusted for age, sex, ethnicity, and socioeconomic status (SES) using the Index of Multiple Deprivation (IMD), and nested using random effects within general practices. Ethnicity was defined using the Office for National Statistics ethnicity categories: White, Mixed, Asian, Black, and Other (including Arab people and other groups not classified elsewhere). From the primary care adult population (n = 1,238,909), we identified a cohort of 84,452 (5.29%) adults with T2D. The mean age of people with T2D in the included cohort at 31 December 2016 was 68.7 ± 12.6 years; 21,656 (43.9%) were female. The mean body mass index was 30.7 ± SD 6.4 kg/m2. The most deprived groups (IMD quintiles 1 and 2) showed poorer HbA1c than the least deprived (IMD quintile 5). People of Black ethnicity had worse HbA1c than those of White ethnicity. Asian individuals were less likely than White individuals to be prescribed insulin (odds ratio OR 0.86, 95% CI 0.79-0.95; p < 0.01), sodium-glucose cotransporter-2 (SGLT2) inhibitors (OR 0.68, 95% CI 0.58-0.79; p < 0.001), and glucagon-like peptide-1 (GLP-1) agonists (OR 0.37, 95% CI 0.31-0.44; p < 0.001). Black individuals were less likely than White individuals to be prescribed SGLT2 inhibitors (OR 0.50, 95% CI 0.39-0.65; p < 0.001) and GLP-1 agonists (OR 0.45, 95% CI 0.35-0.57; p < 0.001). Individuals in IMD quintile 5 were more likely than those in the other IMD quintiles to have annual testing for HbA1c, BP, eGFR, retinopathy, and neuropathy. Black individuals were less likely than White individuals to have annual testing for HbA1c (OR 0.89, 95% CI 0.79-0.99; p = 0.04) and retinopathy (OR 0.82, 95% CI 0.70-0.96; p = 0.011). Asian individuals were more likely than White individuals to have monitoring for HbA1c (OR 1.10, 95% CI 1.01-1.20; p = 0.023) and eGFR (OR 1.09, 95% CI 1.00-1.19; p = 0.048), but less likely for retinopathy (OR 0.88, 95% CI 0.79-0.97; p = 0.01) and neuropathy (OR 0.88, 95% CI 0.80-0.97; p = 0.01). The study is limited by the nature of being observational and defined using retrospectively collected data. Disparities in diabetes care may show regional variation, which was not part of this evaluation.
Our findings suggest that disparity in glycaemic control, diabetes-related monitoring, and prescription of newer therapies remains a challenge in diabetes care. Both SES and ethnicity were important determinants of inequality. Disparities in glycaemic control and other areas of care may lead to higher rates of complications and adverse outcomes for some groups.
Weight loss, hyperglycaemia and diabetes are known features of pancreatic cancer. We quantified the timing and the amount of changes in body mass index (BMI) and glycated haemoglobin (HbA1c), and ...their association with pancreatic cancer from five years before diagnosis.
A matched case-control study was undertaken within 590 primary care practices in England, United Kingdom. 8,777 patients diagnosed with pancreatic cancer (cases) between 1st January 2007 and 31st August 2020 were matched to 34,979 controls by age, gender and diabetes. Longitudinal trends in BMI and HbA1c were visualised. Odds ratios adjusted for demographic and lifestyle factors (aOR) and 95% confidence intervals (CI) were calculated with conditional logistic regression. Subgroup analyses were undertaken according to the diabetes status.
Changes in BMI and HbA1c observed for cases on longitudinal plots started one and two years (respectively) before diagnosis. In the year before diagnosis, a 1 kg/m2 decrease in BMI between cases and controls was associated with aOR for pancreatic cancer of 1.05 (95% CI 1.05 to 1.06), and a 1 mmol/mol increase in HbA1c was associated with aOR of 1.06 (1.06 to 1.07). ORs remained statistically significant (p < 0.001) for 2 years before pancreatic cancer diagnosis for BMI and 3 years for HbA1c. Subgroup analysis revealed that the decrease in BMI was associated with a higher pancreatic cancer risk for people with diabetes than for people without (aORs 1.08, 1.06 to 1.09 versus 1.04, 1.03 to 1.05), but the increase in HbA1c was associated with a higher risk for people without diabetes than for people with diabetes (aORs 1.09, 1.07 to 1.11 versus 1.04, 1.03 to 1.04).
The statistically significant changes in weight and glycaemic control started three years before pancreatic cancer diagnosis but varied according to the diabetes status. The information from this study could be used to detect pancreatic cancer earlier than is currently achieved. However, regular BMI and HbA1c measurements are required to facilitate future research and implementation in clinical practice.
Sodium-glucose co-transporter-2 inhibitors (SGLT-2is) are licenced for initiation for glucose lowering in people with type 2 diabetes (T2DM) with an estimated glomerular filtration rate (eGFR) ≥ ...60 mL/min/1.73m
). However, recent trial data have shown that these medications have renal and cardio-protective effects, even for impaired kidney function. The extent to which trial evidence and updated guidelines have influenced real-world prescribing of SGLT-2is is not known, particularly with co-administration of diuretics.
We performed a cross-sectional analysis of people with T2DM registered with practices in the Oxford-Royal College of General Practitioners (RCGP) Research and Surveillance Centre (RSC) database on the 31st July 2019. We calculated the percentage of people prescribed SGLT-2is according to eGFR categories (< 45, 45-59, and ≥ 60 mL/min/1.73m
), with a heart failure diagnosis and stratified by body mass index categories (underweight, normal weight, overweight, obese), and with concomitant prescription of a diuretic. Multilevel logistic regression analysis was performed to determine whether heart failure diagnosis and renal function were associated with SGLT-2i prescribing.
From a population of 242,624 people with T2DM across 419 practices, 11.0% (n = 26,700) had been prescribed SGLT-2is. The majority of people initiated SGLT-2is had an eGFR ≥ 60 mL/min/1.73m
(93.2%), and 4.3% had a heart failure diagnosis. 9,226 (3.8%) people were prescribed SGLT-2is as an add-on to their diuretic prescription. People in the highest eGFR category (≥ 60 mL/min/1.73m
) were more likely to be prescribed SGLT-2is than those in eGFR lower categories. Overweight (OR 2.05, 95% CI 1.841-2.274) and obese people (OR 3.84, 95% CI 3.472-4.250) were also more likely to be prescribed these medications, whilst use of diuretics (OR 0.74, 95% CI 0.682-0.804) and heart failure (OR 0.81, 95% CI 0.653-0.998) were associated with lower odds of being prescribed SGLT-2is.
Prescribing patterns of SGLT-2is for glucose lowering in T2DM in primary care generally concur with licenced indications according to recommended renal thresholds. A small percentage of people with heart failure were prescribed SGLT-2is for T2DM. An updated analysis is merited should UK National Institute for Health Care and Excellence prescribing guidelines for T2DM be revised to incorporate new data on the benefits for those with reduced renal function or with heart failure.
High serum phosphate is associated with coronary artery disease in patients with normal and impaired renal function. We asked: Does the serum phosphate range provide prediction of primary cardiac ...events? We extracted coded primary care data for over 100,000 patients from a database of 135 primary medical practices. Patients aged between 18 and 90 years without pre-existing cardiovascular diagnoses were included from a potential sample of over 1·2 million individuals.
Binary logistic regression models were used to evaluate the contribution of QRISK factors and electrolytes, including serum phosphate, to cardiac outcomes at five and nine years following an initial phosphate measurement. At five-year review (n = 113,993), low serum phosphate (OR 1·75, 95%CI 1·36-2·23, p<0·001), high-normal (OR 1·50, 95%CI 1·29-1·74, p<0·001), and high serum phosphate (OR 1·74, 95%CI 1·06-2·70, p = 0·02) were long-term risk factors for primary cardiac disease events after adjusting for confounding variables. A similar pattern was seen at our nine-year review.
The extremes of serum phosphate may confer cardiac event risk with a U-shaped trend. In particular, we raise new cardiac concerns for low serum phosphate in the general population. Also, the normal range for phosphate may require redefinition among healthy adults.
Several new classes of glucose-lowering medications have been introduced in the past two decades. Some, such as sodium-glucose cotransporter 2 inhibitors (SGLT2s), have evidence of improved ...cardiovascular outcomes, while others, such as dipeptidyl peptidase-4 inhibitors (DPP4s), do not. It is therefore important to identify their uptake in order to find ways to support the use of more effective treatments.
To analyse the uptake of these new classes among patients with type 2 diabetes.
This was a retrospective repeated cross-sectional analysis in primary care. Rates of medication uptake in Australia, Canada, England, and Scotland were compared.
Primary care Electronic Medical Data on prescriptions (Canada, UK) and dispensing data (Australia) from 2012 to 2017 were used. Individuals aged ≥40 years on at least one glucose-lowering drug class in each year of interest were included, excluding those on insulin only. Proportions of patients in each nation, for each year, on each class of medication, and on combinations of classes were determined.
Data from 238 619 patients were included in 2017. The proportion of patients on sulfonylureas (SUs) decreased in three out of four nations, while metformin decreased in Canada. Use of combinations of metformin and new drug classes increased in all nations, replacing combinations involving SUs. In 2017, more patients were on DPP4s (between 19.1% and 27.6%) than on SGLT2s (between 10.1% and 15.3%).
New drugs are displacing SUs. However, despite evidence of better outcomes, the adoption of SGLT2s lagged behind DPP4s.
Randomised controlled trials (RCTs) are the gold standard for evidence-based practice. However, RCTs can have limitations. For example, translation of findings into practice can be limited by design ...features, such as inclusion criteria, not accurately reflecting clinical populations. In addition, it is expensive to recruit and follow-up participants in RCTs. Linkage with routinely collected data could offer a cost-effective way to enhance the conduct and generalisability of RCTs. The aim of this study is to investigate how primary care data can support RCTs.
Secondary analysis following linkage of two datasets: 1) multicentre CHHiP radiotherapy trial (ISRCTN97182923) and 2) primary care database from the Royal College of General Practitioners Research and Surveillance Centre. Comorbidities and medications recorded in CHHiP at baseline, and radiotherapy-related toxicity recorded in CHHiP over time were compared with primary care records. The association of comorbidities and medications with toxicity was analysed with mixed-effects logistic regression.
Primary care records were extracted for 106 out of 2811 CHHiP participants recruited from sites in England (median age 70, range 44 to 82). Complementary information included longitudinal body mass index, blood pressure and cholesterol, as well as baseline smoking and alcohol usage but was limited by the considerable missing data. In the linked sample, 9 (8%) participants were recorded in CHHiP as having a history of diabetes and 38 (36%) hypertension, whereas primary care records indicated incidence prior to trial entry of 11 (10%) and 40 (38%) respectively. Concomitant medications were not collected in CHHiP but available in primary care records. This indicated that 44 (41.5%) men took aspirin, 65 (61.3%) statins, 14 (13.2%) metformin and 46 (43.4%) phosphodiesterase-5-inhibitors at some point before or after trial entry.
We provide a set of recommendations on linkage and supplementation of trials. Data recorded in primary care are a rich resource and linkage could provide near real-time information to supplement trials and an efficient and cost-effective mechanism for long-term follow-up. In addition, standardised primary care data extracts could form part of RCT recruitment and conduct. However, this is at present limited by the variable quality and fragmentation of primary care data.
To describe trends in modifiable and non-modifiable unfavorable factors affecting pregnancy outcomes, over time (years 2004-2017), in women with diabetes of childbearing age from an English primary ...care perspective.
We identified women with diabetes aged 16-45 years from the Royal College of General Practitioners (RCGP) Research and Surveillance Centre (RSC) network, an English primary care sentinel database. Repeated annual cross-sectional analyses (2004-2017) assessed the prevalence of unfavorable factors for pregnancy, such as obesity, poor glycaemic control, microalbuminuria, hypertension, use of medications for treating diabetes, and associated comorbidities not recommended for pregnancy.
We identified 3,218 women (61.5% with Type 2 diabetes) in 2004 and 6,657 (65.0% with Type 2 diabetes) in 2017. The proportion of women with ideal glycaemic control for conception (HbA1c<6.5%) increased over time, in patients with Type 1 diabetes from 9.0% (7.1%-11.0%) to 19.1% (17.2%-21.1%), and in those with Type 2 diabetes from 27.2% (24.6%-29.9%) to 35.4% (33.6%-37.1%). The proportion of women with Type 2 diabetes prescribed medications different from insulin and metformin rose from 22.3% (20.5%-24.2%) to 27.3% (26.0%-28.6%).In 2017, 14.0% (12.6%-15.4%) of women with Type 1 and 30.7% (29.3%-32.0%) with Type 2 diabetes were prescribed angiotensin-modulating antihypertensives or statins. We captured at least one unfavorable factor for pregnancy in 50.9% (48.8%-52.9%) of women with Type 1 diabetes and 70.7% (69.3%-72.0%) of women with Type 2 diabetes. Only one third of women with Type 1 diabetes (32.2%, 30.3%-34.0%) and a quarter of those with Type 2 diabetes (23.1%, 21.9%-24.4%) were prescribed hormonal contraception. Contraception was prescribed more frequently to women with unfavorable factors for pregnancy compared to those without, however, the difference was significant only for women with Type 1 diabetes.
Despite significant improvements in general diabetes care, the majority of women with Type 1 or Type 2 diabetes have unfavorable, although mostly modifiable, factors for the start of pregnancy. Good diabetes care for women of childbearing age should include taking into consideration a possible pregnancy.
In the UK, type 2 diabetes mellitus (T2D) is largely managed in primary care. Delay in the intensification to injectable therapy, a form of clinical inertia, is associated with worse glycaemic ...control. UK general practice is highly computerised, with care being recorded on computerised medical record systems; this allows for quantitative analysis of clinical care but not of the underpinning decision-making process. The aim of this study is to investigate perceptions of patients and clinicians in primary care on the initiation of injectable therapies in T2D, and the context within which those decisions are made.
This is a mixed methods study, taking a "realist evaluation" approach. The qualitative components comprise focus groups, interviews, and video recordings of simulated surgeries; the quantitative analysis: an overview of participating practices, elements of the video recording, and an online survey. We will recruit primary care clinicians (general practitioners and nurses) and patients from a representative sample of practices within the Royal College of General Practitioners (RCGP) Research and Surveillance Centre (RSC) network. Participants will be patients with T2D, and primary care clinicians. Focus groups and semi-structured interviews will be recorded, transcribed verbatim and analysed using Framework Analysis. The simulated surgeries will include cases that might be escalated to injectable therapy. The consultation will be reviewed using the Calgary-Cambridge model to assess communication and determination of adherence to national prescribing guidelines. We will conduct multi-channel video recording including screen capture, clinician and patient facial expressions, wide angle view of the consultation, and the computerised medical record screen. This allows annotation and qualitative analysis of the video recordings, and statistical analyses for the quantitative data. We will also conduct an online survey of primary care clinicians' attitudes to, and perceptions of, initiation of injectable therapies, which will be analysed using summary statistics.
Results aim to provide a detailed insight into the dynamic two-way decision-making process underpinning use of injectable therapy for T2D. The study will provide insights into clinical practice and enable the development of training, interventions and guidelines that may facilitate, where appropriate, the intensification to injectable therapy.
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