Glycaemic control in patients with type 2 diabetes initiating second-line therapy: Results from the global DISCOVER study programme.

AIM: To assess glycaemic control and factors associated with poor glycaemic control at initiation of second-line therapy in the DISCOVER programme. MATERIALS AND METHODS: DISCOVER (NCT02322762 and NCT02226822) comprises two similar prospective observational studies of 15 992 people with type 2 diabetes (T2D) initiating second-line glucose-lowering therapy in 38 countries across six regions (Africa, Americas, South-East Asia, Eastern Mediterranean, Europe and Western Pacific). Data were collected using a standardized case report form. Glycated haemoglobin (HbA1c) levels were measured according to standard clinical practice in each country, and factors associated with poor glycaemic control (HbA1c >8.0%) were evaluated using hierarchical regression models. RESULTS: HbA1c levels were available for 80.9% of patients (across-region range [ARR] 57.5%-97.5%); 92.2% (ARR 59.2%-99.1%) of patients had either HbA1c or fasting plasma glucose levels available. The mean HbA1c was 8.3% (ARR 7.9%-8.7%). In total, 26.7% of patients had an HbA1c level ≥9.0%, with the highest proportions in South-East Asia (35.6%). Factors associated with having HbA1c >8.0% at initiation of second-line therapy included low education level, low country income, and longer time since T2D diagnosis. CONCLUSIONS: The poor levels of glycaemic control at initiation of second-line therapy suggest that intensification of glucose-lowering treatment is delayed in many patients with T2D. In some countries, HbA1c levels are not routinely measured. These findings highlight an urgent need for interventions to improve monitoring and management of glycaemic control worldwide, particularly in lower-middle- and upper-middle-income countries

Vascular complications in patients with type 2 diabetes: prevalence and associated factors in 38 countries (the DISCOVER study program).

BACKGROUND: The global prevalence of type 2 diabetes-related complications is not well described. We assessed prevalence of vascular complications at baseline in DISCOVER (NCT02322762; NCT02226822), a global, prospective, observational study program of 15,992 patients with type 2 diabetes initiating second-line therapy, conducted across 38 countries. METHODS: Patients were recruited from primary and specialist healthcare settings. Data were collected using a standardized case report form. Prevalence estimates of microvascular and macrovascular complications at baseline were assessed overall and by country and region, and were standardized for age and sex. Modified Poisson regression was used to assess factors associated with the prevalence of complications. RESULTS: The median duration of type 2 diabetes was 4.1 years (interquartile range [IQR]: 1.9-7.9 years), and the median glycated hemoglobin (HbA1c) level was 8.0% (IQR: 7.2-9.1%). The crude prevalences of microvascular and macrovascular complications were 18.8% and 12.7%, respectively. Common microvascular complications were peripheral neuropathy (7.7%), chronic kidney disease (5.0%), and albuminuria (4.3%). Common macrovascular complications were coronary artery disease (8.2%), heart failure (3.3%) and stroke (2.2%). The age- and sex-standardized prevalence of microvascular complications was 17.9% (95% confidence interval [CI] 17.3-18.6%), ranging from 14.2% in the Americas to 20.4% in Europe. The age- and sex-standardized prevalence of macrovascular complications was 9.2% (95% CI 8.7-9.7%), ranging from 4.1% in South-East Asia to 18.8% in Europe. Factors positively associated with vascular complications included age (per 10-year increment), male sex, diabetes duration (per 1-year increment), and history of hypoglycemia, with rate ratios (95% CIs) for microvascular complications of 1.14 (1.09-1.19), 1.30 (1.20-1.42), 1.03 (1.02-1.04) and 1.45 (1.25-1.69), respectively, and for macrovascular complications of 1.41 (1.34-1.48), 1.29 (1.16-1.45), 1.02 (1.01-1.02) and 1.24 (1.04-1.48), respectively. HbA1c levels (per 1.0% increment) were positively associated with microvascular (1.05 [1.02-1.08]) but not macrovascular (1.00 [0.97-1.04]) complications. CONCLUSIONS: The global burden of microvascular and macrovascular complications is substantial in these patients with type 2 diabetes who are relatively early in the disease process. These findings highlight an opportunity for aggressive early risk factor modification, particularly in regions with a high prevalence of complications. Trial registration ClinicalTrials.gov; NCT02322762. Registered 23 December 2014. https://clinicaltrials.gov/ct2/show/NCT02322762 . ClinicalTrials.gov; NCT02226822. Registered 27 August 2014. https://clinicaltrials.gov/ct2/show/NCT02226822

Treatment patterns and associated factors in 14 668 people with type 2 diabetes initiating a second-line therapy: Results from the global DISCOVER study programme.

AIM: To evaluate treatment data from DISCOVER (NCT02322762 and NCT02226822), a global, prospective, observational study programme of patients with type 2 diabetes initiating a second-line glucose-lowering therapy. MATERIALS AND METHODS: Data were collected using a standardized case report form. First- and second-line treatments were assessed in 14 668 patients from 37 countries across six regions. Among patients prescribed first-line metformin monotherapy, Firth logistic regression models were used to assess factors associated with second-line treatment choices. RESULTS: The most common first-line therapies were metformin monotherapy (57.9%) and combinations of metformin with a sulphonylurea (14.6%). The most common second-line therapies were combinations of metformin with other agents (72.2%), including dipeptidyl peptidase-4 (DPP-4) inhibitors (25.1%) or sulphonylureas (21.3%). Among patients prescribed first-line metformin monotherapy, the most common second-line therapies were combinations of metformin with a DPP-4 inhibitor [32.8%; across-region range (ARR): 2.4%-51.3%] or a sulphonylurea (30.0%; ARR: 18.3%-63.6%); only a few patients received combinations of metformin with sodium-glucose co-transporter-2 inhibitors (6.7%; ARR: 0.0%-10.8%) or glucagon-like peptide-1 receptor agonists (1.9%; ARR: 0.1%-4.5%). Both clinical and non-medical factors were associated with choice of second-line therapy after metformin monotherapy. CONCLUSIONS: Fewer patients than expected received metformin monotherapy at first line, and the use of newer therapies at second line was uncommon in some regions of the world. Patients' socioeconomic status was associated with treatment patterns, suggesting that therapy choices are influenced by cost and access

Triple versus guideline antiplatelet therapy to prevent recurrence after acute ischaemic stroke or transient ischaemic attack: the TARDIS RCT.

BACKGROUND: Two antiplatelet agents are better than one for preventing recurrent stroke after acute ischaemic stroke or transient ischaemic attack (TIA). Therefore, intensive treatment with three agents might be better still, providing it does not cause undue bleeding. OBJECTIVE: To compare the safety and efficacy of intensive therapy with guideline antiplatelet therapy for acute ischaemic stroke and TIA. DESIGN: International prospective randomised open-label blinded end-point parallel-group superiority clinical trial. SETTING: Acute hospitals at 106 sites in four countries. PARTICIPANTS: Patients > 50 years of age with acute non-cardioembolic ischaemic stroke or TIA within 48 hours of ictus (stroke). INTERVENTIONS: Participants were allocated at random by computer to 1 month of intensive (combined aspirin, clopidogrel and dipyridamole) or guideline (combined aspirin and dipyridamole, or clopidogrel alone) antiplatelet agents, and followed for 90 days. MAIN OUTCOME MEASURES: The primary outcome was the incidence and severity of any recurrent stroke (ischaemic, haemorrhagic; assessed using the modified Rankin Scale) or TIA within 90 days by blinded telephone follow-up. Analysis using ordinal logistic regression was by intention to treat. Other outcomes included bleeding and its severity, death, myocardial infarction (MI), disability, mood, cognition and quality of life. RESULTS: The trial was stopped early on the recommendation of the Data Monitoring Committee after recruitment of 3096 participants (intensive, n = 1556; guideline, n = 1540) from 106 hospitals in four countries between April 2009 and March 2016. The incidence and severity of recurrent stroke or TIA did not differ between intensive and guideline therapy in 3070 (99.2%) participants with data [93 vs. 105 stroke/TIA events; adjusted common odds ratio 0.90, 95% confidence interval (CI) 0.67 to 1.20; p = 0.47]. Major (encompassing fatal) bleeding was increased with intensive as compared with guideline therapy [39 vs. 17 participants; adjusted hazard ratio (aHR) 2.23, 95% CI 1.25 to 3.96; p = 0.006]. There were no differences between the treatment groups in all-cause mortality, or the composite of death, stroke, MI and major bleeding (aHR 1.02, 95% CI 0.77 to 1.35; p = 0.88). LIMITATIONS: Patients and investigators were not blinded to treatment. The comparator group comprised two guideline strategies because of changes in national guidelines during the trial. The trial was stopped early, thereby reducing its statistical power. CONCLUSIONS: The use of three antiplatelet agents is associated with increased bleeding without any significant reduction in recurrence of stroke or TIA. FUTURE WORK: The safety and efficacy of dual antiplatelet therapy (combined aspirin and clopidogrel) versus aspirin remains to be defined. Further research is required on identifying individual patient response to antiplatelets, and the relationship between response and the subsequent risks of vascular recurrent events and bleeding complications. TRIAL REGISTRATION: Current Controlled Trials ISRCTN47823388. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 22, No. 48. See the NIHR Journal Library website for further project information. The Triple Antiplatelets for Reducing Dependency after Ischaemic Stroke (TARDIS) vanguard phase was funded by the British Heart Foundation (grant PG/08/083/25779, from 1 April 2009 to 30 September 2012) and indirect funding was provided by the Stroke Association through its funding of the Stroke Trials Unit, Division of Clinical Neuroscience, University of Nottingham, Nottingham, UK. There was no commercial support for the trial and antiplatelet drugs were sourced locally at each site. The trial was sponsored by the University of Nottingham