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Aims: To describe glucose‐lowering treatment regimens and glycated haemoglobin (HbA1c) trajectories in individuals with type 2 diabetes (T2D) over 36 months of follow‐up from the start of second‐line therapy. Materials and Methods: This data analysis from the 3‐year, observational DISCOVER study programme included 14 687 participants from 37 countries with T2D initiating second‐line glucose‐lowering therapy. Treatment and HbA1c data were collected at baseline (start of second‐line therapy) and at 6, 12, 24 and 36 months. Treatment regimen changes over follow‐up were analysed using the McNemar test, with carry‐forward imputation for intermediate missing values. Results: A total of 11 592 participants had treatment data at baseline and 36 months, and 11 882 had HbA1c data at baseline. At baseline and 36 months, respectively, rates of oral monotherapy use were 12.1% and 12.4% (P = 0.22), rates of dual oral therapy use were 63.4% and 47.6% (P < 0.0001), rates of ≥ triple oral therapy use were 17.5% and 25.4% (P < 0.0001), and rates of injectable treatment use were 7.0% and 13.7% (P < 0.0001). Use of injectable drugs was most common among participants with an HbA1c level ≥64 mmol/mol (≥8.0%). Overall, 42.9% of participants changed treatment during follow‐up. Mean HbA1c levels at baseline and 6 months were 67 mmol/mol (8.3%) and 55 mmol/mol (7.2%), respectively, remaining stable thereafter. Conclusions: Dual oral therapy was the most common treatment regimen at the start of second‐line treatment, and over half of the participants remained on the same treatment during follow‐up. [ABSTRACT FROM AUTHOR]

DISCOVER is a 3-year observational study program of 15,983 people with type 2 diabetes initiating second-line glucose-lowering therapy in 38 countries. We investigated the association between socioeconomic status and both the availability of a baseline glycated hemoglobin (HbA1c) measurement and poor glycemic control (HbA1c level ≥ 9.0%) in participants enrolled in DISCOVER. Factors associated with a lack of baseline HbA1c measurement or an HbA1c level ≥ 9.0% were assessed using three-level hierarchical logistic models. Overall, 19.1% of participants did not have a baseline HbA1c measurement recorded. Lower-middle country income (vs. high) and primary/no formal education (vs. university education) were independently associated with a reduced likelihood of having a baseline HbA1c measurement (odds ratio [95% confidence interval]: 0.11 [0.03–0.49] and 0.81 [0.66–0.98], respectively. Of the participants with an available HbA1c measurement, 26.9% had an HbA1c level ≥ 9.0%; 68.7% of these individuals were from lower- or upper-middle-income countries. Factors associated with an increased likelihood of poor glycemic control included low country income, treatment at a site with public and/or governmental funding (vs. private funding) and having public or no health insurance (vs. private). A substantial proportion of DISCOVER participants did not have an HbA1c measurement; more than one-quarter of these participants had poorly controlled type 2 diabetes. Both individual- and country-level socioeconomic factors are associated with the quality of care regarding glycemic control. Awareness of these factors could help improve the management of patients with type 2 diabetes. [ABSTRACT FROM AUTHOR]

Aims: Glycaemic control is a cornerstone of type 2 diabetes (T2D) management. We assessed factors associated with good long‐term glycaemic control in patients with glycated haemoglobin (HbA1c) ≥7.0% at initiation of second‐line glucose‐lowering therapy, using data from DISCOVER, a global, prospective, 3‐year observational study of patients with T2D. Materials and Methods: This analysis included patients with HbA1c ≥7.0% at baseline (initiation of second‐line therapy). Multivariable regression models assessed factors associated with having HbA1c <7.0% at 3 years in two distinct groups: patients with (a) HbA1c ≥7.0% and <9.0%, and (b) HbA1c ≥9.0% at baseline. Results: In total, 7575 patients with baseline HbA1c ≥7.0% were included (2233 with baseline HbA1c ≥9.0%). At 6 months, 43.7% and 24.2% of patients had an HbA1c level <7.0% in groups a and b, respectively; the corresponding proportions at 3 years were 45.8% and 29.3%. Having HbA1c <7.0% at 6 months (vs. ≥7.0%) was the strongest predictor of having HbA1c <7.0% at 3 years in both group a and group b [odds ratio (95% confidence interval): 2.01 (1.77‐2.27) and 2.68 (2.10‐3.41), respectively]. Longer T2D duration was associated with a decreased likelihood of having HbA1c <7.0% at 3 years. Conclusions: In patients with poor glycaemic control at initiation of second‐line therapy, early attainment of HbA1c <7.0% appears predictive of long‐term glycaemic control, suggesting that timely modification of treatment strategies in patients with elevated HbA1c after 6 months is important to minimize therapeutic inertia. [ABSTRACT FROM AUTHOR]

Aim: To explore the effects of second‐line combination therapies with metformin on body weight, HbA1c and health‐related quality of life, as well as the risks of hypoglycaemia and further treatment intensification in the DISCOVER study, a 3‐year, prospective, global observational study of patients with type 2 diabetes initiating second‐line glucose‐lowering therapy. Materials and Methods: Adjusted changes from baseline in weight, HbA1c and 36‐item Short Form Health Survey version 2 (SF‐36v2) summary scores at 6, 12, 24 and 36 months were assessed using linear mixed models. Risk of hypoglycaemia and further intensification were assessed using interval censored analyses. Results: At baseline, 7613 patients received metformin in combination with a sulphonylurea (SU; 40.9%), a dipeptidyl peptidase‐4 (DPP‐4) inhibitor (48.3%), a sodium‐glucose co‐transporter‐2 (SGLT‐2) inhibitor (8.3%) or a glucagon‐like peptide‐1 (GLP‐1) receptor agonist (2.4%). After 36 months, all combinations showed similar reductions in HbA1c (0.8%‐1.0%), however, metformin plus a DPP‐4 inhibitor, an SGLT‐2 inhibitor or a GLP‐1 receptor agonist was associated with greater weight loss (1.9, 2.9 and 5.0 kg, respectively) than metformin plus an SU (1.3 kg, P <.0001). Proportions of further treatment intensification were similar across combinations (19.9%‐26.2%). Patients prescribed metformin plus an SU more often reported one or more hypoglycaemic events (11.9%) than other combinations (3.9%‐6.4%, P <.0001). SF‐36v2 summary scores were typically lowest among patients prescribed metformin and an SU. Conclusions: Combinations of metformin with an SU were associated with the lowest weight reduction, highest risk of hypoglycaemia and lower SF‐36v2 scores. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Generalizability of findings from cardiovascular outcomes trials (CVOTs) to patients with type 2 diabetes (T2D) in clinical practice is unknown. We assessed the proportions of patients in the Diabetes Collaborative Registry who would have met enrolment criteria for pivotal CVOTs of sodium‐glucose co‐transporter‐2 inhibitors (SGLT‐2is): EMPA‐REG OUTCOME, CANVAS, DECLARE and VERTIS CV. In 172 643 patients, mean [standard deviation (SD)] age and HbA1c were 68.1 (11.8) years and 7.8% (2.2), respectively; 56.8% of patients were men and SGLT‐2i use was 4.4%. Atherosclerotic cardiovascular disease (ASCVD) prevalence was 64.3% and mean 10‐year ASCVD risk was 28.6% in patients without ASCVD. Proportions of patients eligible for CVOTs ranged from 26% (EMPA‐REG OUTCOME) to 44% (DECLARE); 48% of patients were ineligible for all CVOTs. Mean (SD) ASCVD risk was 25.4% (22.6), 32.1% (20.6) and 37.7% (19.4) in patients eligible for no, one or two CVOTs, respectively. SGLT‐2i use was low in patients eligible for no CVOTs (3.5%) and at least one CVOT (5.2%). In conclusion, applicability of CVOT results to patients with T2D in clinical practice varies based on trial eligibility criteria. [ABSTRACT FROM AUTHOR]

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 [ABSTRACT FROM AUTHOR]

Aims: To describe the characteristics and treatment of patients with type 2 diabetes mellitus initiating a second-line glucose-lowering therapy in the global DISCOVER study programme.Methods: DISCOVER comprises two similar 3-year prospective observational studies (NCT02322762 and NCT02226822), involving 15,992 patients initiating a second-line glucose-lowering therapy in 38 countries across six regions (Africa, Americas, South-East Asia, Eastern Mediterranean, Europe and Western Pacific).Results: Overall, 54.2% of patients were male (across region range [ARR]: 37.7-58.6%). At baseline, mean age and time since diagnosis of type 2 diabetes mellitus were 57.2 (ARR: 53.1-61.9)and 5.6 (ARR: 4.6-6.9) years, respectively. Median glycated haemoglobin (HbA1c) was 63.9 mmol/mol (8.0%; ARR: 7.6-8.3%). Microvascular and macrovascular complications were reported in 18.9% (ARR: 14.5-23.5%) and 12.7% (ARR: 5.0-26.6%) of patients, respectively. First-line treatments were mostly metformin monotherapy (55.6%; ARR: 42.5-83.6%) and combinations of metformin with a sulfonylurea (14.4%; ARR: 5.8-31.1%). The most commonly prescribed second-line therapies were combinations of metformin with a dipeptidyl peptidase-4 inhibitor (23.5%; ARR: 2.2-29.6%) or a sulfonylurea (20.9%; ARR: 13.6-57.1%).Conclusions: DISCOVER demonstrates considerable global variation in the treatment of type 2 diabetes mellitus, and a need for more aggressive risk factor control. [ABSTRACT FROM AUTHOR]

Aims: To assess the effects of glycated haemoglobin (HbA1c) levels at time of glucose-lowering treatment intensification in DISCOVER, a global observational study of patients with type 2 diabetes (T2D) initiating second-line therapy. Outcomes of interest were glycaemic control, hypoglycaemia, and need for further intensification during 3 years of follow-up.Methods: We included patients who intensified treatment (add-on or insulin initiation) upon initiation of second-line therapy (baseline). Outcomes were assessed according to baseline HbA1c: HbA1c ≤ 7·5% (early intensification) or HbA1c > 7·5% (late intensification). Factors associated with early or late intensification were assessed using multivariate logistic regression.Results: Of the 9575 patients included, 3275 (34·2%) intensified treatment early and 6300 (65·8%) intensified treatment late. During follow-up, mean (SD) HbA1c was lower in the early- than in the late-intensification group (6·9% [0·95%] vs 7·5% [1·28%] at 36 months). More patients had HbA1c < 7·0% in the early- than in the late-intensification group (61·8% vs 37·9% at 36 months; p < 0·001). The risk of further intensification was higher in the late-intensification group (hazard ratio 1·88 [95% confidence interval 1·68-2·09]). Occurrence of hypoglycaemia was similar in both groups.Conclusions: Late intensification of glucose-lowering therapy after first-line treatment failure reduces the likelihood of reaching recommended treatment goals. [ABSTRACT FROM AUTHOR]