Changing use of antidiabetic drugs in the UK: trends in prescribing 2000-2017.

Guidelines for the use of drugs for type 2 diabetes mellitus (T2DM) have changed since 2000, and new classes of drug have been introduced. Our aim was to describe how drug choice at initiation and first stage of intensification have changed over this period, and to what extent prescribing was in accord with clinical guidelines, including adherence to recommendations regarding kidney function. Repeated cross-sectional study. UK electronic primary care health records from the Clinical Practice Research Datalink. Adults initiating treatment with a drug for T2DM between January 2000 and July 2017. The primary outcomes were the proportion of each class of T2DM drug prescribed for initiation and first-stage intensification in each year. We also examined drug prescribing by kidney function and country within the UK. Of 280 241 people initiating treatment with T2DM drugs from 2000 to 2017, 73% (204 238/280 241) initiated metformin, 15% (42 288/280 241) a sulfonylurea, 5% (12 956/280 241) with metformin and sulfonylurea dual therapy and 7% (20 759/280 241) started other options. Clinicians have increasingly prescribed metformin at initiation: by 2017 this was 89% (2475/2778) of drug initiations. Among people with an estimated glomerular filtration rate of ≤30 mL/min/1.73 m2, the most common drug at initiation was a sulfonylurea, 58% (659/1135). In 2000, sulfonylureas were the predominant drug at the first stage of drug intensification (87%, 534/615) but by 2017 this fell to 30% (355/1183) as the use of newer drug classes increased. In 2017, new prescriptions for dipeptidyl peptidase-4 inhibitors (DPP4i) and sodium/glucose cotransporter-2 inhibitors (SGLT2i) accounted for 42% (502/1183) and 22% (256/1183) of intensification drugs, respectively. Uptake of new classes differs by country with DPP4is and SGLT2is prescribed more in Northern Ireland and Wales than England or Scotland. Our findings show markedly changing prescribing patterns for T2DM between 2000 and 2017, largely consistent with clinical guidelines.

Wilkinson S ，Douglas I ，Stirnadel-Farrant H ，Fogarty D ，Pokrajac A ，Smeeth L ，Tomlinson L ... -  《BMJ Open》

Patterns of initial and first-intensifying antidiabetic drug utilization among patients with type 2 diabetes mellitus in Scotland, 2010-2020: A retrospective population-based cohort study.

To evaluate the utilization and prescribing patterns of antidiabetic drugs (ADDs) for patients with type 2 diabetes mellitus (T2DM) at treatment initiation and first intensification. A retrospective cohort study was performed using linked routinely collected data of patients with T2DM who received ADDs between January 2010 and December 2020 in Scotland. The prescribing patterns were quantified using frequency/percentages, absolute/relative change, and trend tests. Overall, 145 909 new ADD users were identified, with approximately 91% (N = 132 382) of patients receiving a single ADD at first treatment initiation. Metformin was the most often prescribed monotherapy (N = 118 737, 89.69%). A total of 50 731 patients (39.40%) who were started on metformin (N = 46 730/118 737, 39.36%) or sulphonylurea (SU; N = 4001/10 029, 39.89%) monotherapy had their treatment intensified with one or more additional ADD. Most initial-metformin (45 963/46 730; 98.36%) and initial-SU users (3894/4001; 97.33%) who added further drugs were intensified with single ADDs. SUs (22 197/45 963; 48.29%) were the most common first-intensifying monotherapy after initial metformin use, but these were replaced by sodium-glucose cotransporter-2 (SGLT2) inhibitors in 2019 (SGLT2 inhibitors: 2039/6065, 33.62% vs. SUs: 1924/6065, 31.72%). Metformin was the most frequently added monotherapy to initial SU use (2924/3894, 75.09%). Although the majority of patients received a single ADD, the use of combination therapy significantly increased over time. Nevertheless, there was a significant increasing trend towards prescribing the newer ADD classes (SGLT2 inhibitors, dipeptidyl peptidase-4 inhibitors) as monotherapy or in combination compared with the older ones (SUs, insulin, thiazolidinediones) at both drug initiation and first intensification. An overall increasing trend in prescribing the newer ADD classes compared to older ADDs was observed. However, metformin remained the most commonly prescribed first-line ADD, while SGLT2 inhibitors replaced SUs as the most common add-on therapy to initial metformin use in 2019.

Mahmoud F ，Mueller T ，Mullen A ，Sainsbury C ，Rushworth GF ，Kurdi A ... -  《-》

Prescribing in Type 2 Diabetes Patients With and Without Cardiovascular Disease History: A Descriptive Analysis in the UK CPRD.

Some classes of glucose-lowering medications, including sodium-glucose co-transporter 2 inhibitors (SGLT2is) and glucagon-like peptide 1-receptor agonists (GLP1-RAs) have cardio-protective benefit, but it is unclear whether this influences prescribing in the United Kingdom (UK). This study aims to describe class-level prescribing in adults with type 2 diabetes mellitus (T2DM) by cardiovascular disease (CVD) history using the Clinical Practice Research Datalink (CPRD). Four cross-sections of people with T2DM aged 18-90 and registered with their general practice for >1 year on 1st January 2017 (n = 166,012), 1st January 2018 (n = 155,290), 1st January 2019 (n = 152,602) and 31st December 2019 (n = 143,373) were identified. Age-standardised proportions for class use through time were calculated separately in those with and without CVD history and by total number of medications prescribed (one, two, three, four+). An analysis by UK country was also performed. Around 31% of patients had CVD history at each cross-section. Metformin was the most common treatment (>70% of those with and without CVD had prescriptions across all treatment lines). Overall use of SGLT2is and GLP1-RAs was low, with slightly less use in patients with CVD (SGLT2i: 9.8% and 13.8% in those with and without CVD respectively; GLP1-RA: 4.3% and 4.9%, December 2019). Use of SGLT2is as part of dual therapy was low but rose throughout the study. In January 2017, estimated use was 8.0% (95% CI 6.9-9.1%) and 8.9% (8.6-9.3%) in those with and without CVD. By December 2019 this reached 18.3% (17.0-19.5%) and 21.2% (20.6-21.7%) for those with and without CVD respectively. SGLT2i use as triple therapy increased: 22.7% (21.0-24.4%) and 25.9% (25.2-26.6%) in January 2017 to 41.3% (39.5-43.0%) and 45.5% (44.7-46.3%) in December 2019. GLP1-RA use also increased, but observed usage remained lower than SGLT2 inhibitors. Insulin use remained stable throughout, with higher use observed in those with CVD (16% vs 9.7% Dec 2019). Time trends in England, Wales, Scotland and Northern Ireland were similar, although class prevalence varied. Although use of SGLT2is and GLP1-RAs has increased, overall usage remains low with slightly lower use in those with CVD history, suggesting there is opportunity to optimise use of these medicines in T2DM patients to manage CVD risk. Insulin use was substantially more prevalent in those with CVD despite no evidence of CVD benefit. Further investigation of factors influencing this finding may highlight strategies to improve patient access to the most appropriate treatments, including those with evidence of cardiovascular benefit.

Farmer RE ，Beard I ，Raza SI ，Gollop ND ，Patel N ，Tebboth A ，McGovern AP ，Kanumilli N ，Ternouth A ... -  《-》

Sodium-glucose co-transporter-2 inhibitors, the latest residents on the block: Impact on glycaemic control at a general practice level in England.

To determine, using published general practice-level data, how differences in Type 2 diabetes mellitus (T2DM) prescribing patterns relate to glycaemic target achievement levels. Multiple linear regression modelling was used to link practice characteristics and defined daily dose (DDD) of different classes of medication in 2015/2016 and changes between that year and the year 2014/2015 in medication to proportion of patients achieving target glycaemic control (glycated haemoglobin A1c [HbA1c] ≤58 mmol/mol [7.5%]) and proportion of patients at high glycaemic risk (HbA1c >86 mmol/mol [10.0%]) for practices in the National Diabetes Audit with >100 people with T2DM on their register. Overall, HbA1c outcomes were not different between the years studied. Although, in percentage terms, most practices increased their use of sodium-glucose co-transporter-2 (SGLT2) inhibitors (96%), dipeptidyl peptidase-4 (DPP-4) inhibitors (76%) and glucagon-like peptide 1 (GLP-1) analogues (53%), there was wide variation in the use of older and newer therapies. For example, 12% of practices used >200% of the national average for some newer agents. In cross-sectional analysis, greater prescribing of metformin and analogue insulin were associated with a higher proportion of patients achieving HbA1c ≤58 mmol/mol; the use of SGLT2 inhibitors and metformin was associated with a reduced proportion of patients with HbA1c >86 mol/mol; otherwise associations for sulphonylureas, GLP-1 analogues, SGLT2 inhibitors and DPP-4 inhibitors were neutral or negative. In year-on-year analysis there was ongoing deterioration in glycaemic control, which was offset to some extent by increased use of SGLT2 inhibitors and GLP-1 analogues, which were associated with a greater proportion of patients achieving HbA1c levels ≤58 mmol/mol and a smaller proportion of patients with HbA1c levels >86 mmol/mol. SGLT2 inhibitor prescribing was associated with significantly greater improvements than those found for GLP-1 analogues. Greater use of newer agents was associated with improvement in glycaemic outcomes but was not sufficient to compensate for the prevailing decline. This may reflect wide variability in the prescribing of newer agents. We found that SGLT inhibitors may be superior to other oral agents in relation to HbA1c outcome. Serious consideration should be given to their use.

Heald AH ，Fryer AA ，Anderson SG ，Livingston M ，Lunt M ，Davies M ，Moreno GYC ，Gadsby R ，Young RJ ，Stedman M ... -  《-》

Factors Associated with Type 2 Diabetes Mellitus Treatment Choice Across Four European Countries.

The aim of this analysis was to identify factors associated with the choice of type 2 diabetes mellitus (T2DM) therapy at the time of intensification of antidiabetic treatment across 4 European countries. Antidiabetic drug prescription/dispensing records and patients' characteristics were obtained from the electronic health care records of patients with T2DM from the Netherlands (NL), Italy, and Spain (ES) (all, 2007-2011); and the United Kingdom (UK; 2008-2012). Oral monotherapy was defined as first-line; oral dual therapy, as second-line; >2 oral treatments or oral combined with an injectable, as third-line; and injectables only, as fourth-line treatment. Treatment intensification was defined as the start of a higher line of treatment. Comedication, comorbidities, clinical parameters, and other factors associated with treatment choice were identified using multivariate relative risk estimation by Poisson regression with robust error variance. In the 5-year study period, 485,120 patients (79% of the treated T2DM population) underwent treatment intensification. Changes in treatment choice were clearly visible over the study period, such as a decline in the use of thiazolidinediones (NL, ES, UK) and increases in the use of dipeptidyl peptidase-4 inhibitors (DPP4i) (NL, ES, UK) and glucagon-like peptide-1 receptor agonists (UK). With first-line treatment, advanced age and renal comorbidity were associated with the use of sulfonylureas (SUs; all countries), whereas high body mass index (BMI) was inversely associated with SU use in the United Kingdom and Spain. With second-line treatment, advanced age was associated with metformin + SU use (all countries); and renal comorbidity with SU + DPP4i use in the United Kingdom and the Netherlands. High BMI was associated with metformin + thiazolidinedione (TZD) use in the United Kingdom and Spain, and with metformin + DPP4i in the United Kingdom. With third-line treatment, advanced age and renal comorbidity were associated with the use of SU + insulin (NL, ES, UK). Hemoglobin A1c >8.5% was positively associated, and high BMI was inversely associated, with the use of any third-line combination containing insulin. Across treatment lines TZD and metformin were negatively associated with renal and cardiac morbidity. Second and third line treatment choices strongly depended on prior treatments. With fourth-line treatment, women were more likely to receive glucagon-like peptide-1 receptor agonists than were men in the United Kingdom and Spain. The results suggest that the main factors driving treatment choice at any stage of intensification were age, hemoglobin A1c, BMI, renal and cardiac morbidity, and treatment history. These drivers were consistent with guidelines on, and contraindications of, specific medications. Differences between countries were generally consistent with, but not solely attributable to, differences in local guidelines and reimbursement policies.

Heintjes EM ，Overbeek JA ，Hall GC ，Prieto-Alhambra D ，Lapi F ，Hammar N ，Bezemer ID ... -  《-》