Aim To conduct a systematic review and meta‐analysis to determine the risk of cardiovascular events and all‐cause mortality associated with sulphonylureas (SUs) vs other glucose lowering drugs in patients with T2DM (T2DM). Materials and methods A systematic review of Medline, Embase, Cochrane and http://clinicaltrials.gov was conducted for studies comparing SUs with placebo or other antihyperglycaemic drugs in patients with T2DM. A cloglog model was used in the Bayesian framework to obtain comparative hazard ratios (HRs) for the different interventions. For the analysis of observational data, conventional fixed‐effect pairwise meta‐analyses were used. Results The systematic review identified 82 randomized controlled trials (RCTs) and 26 observational studies. Meta‐analyses of RCT data showed an increased risk of all‐cause mortality and cardiovascular‐related mortality for SUs compared with all other treatments combined (HR 1.26, 95% confidence interval [CI] 1.10‐1.44 and HR 1.46, 95% CI 1.21‐1.77, respectively). The risk of myocardial infarction was significantly higher for SUs compared with dipeptidyl peptidase‐4 (DPP‐4) inhibitors and sodium‐glucose co‐transporter‐2 inhibitors (HR 2.54, 95% CI 1.14‐6.57 and HR 41.80, 95% CI 1.64‐360.4, respectively). The risk of stroke was significantly higher for SUs than for DPP‐4 inhibitors, glucagon‐like peptide‐1 agonists, thiazolidinediones and insulin. Conclusions The present meta‐analysis showed an association between SU therapy and a higher risk of major cardiovascular disease‐related events compared with other glucose lowering drugs. Results of ongoing RCTs, which should be available in 2018, will provide definitive results on the risk of cardiovascular events and all‐cause mortality associated with SUs vs other antihyperglycaemic drugs.

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%,

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Adherence to NICE guidance for initiating and continuing GLP-1 receptor agonists is low. However, lack of data on ethnicity (for assessing NICE's BMI criteria) and on contraindications and/or hypersensitivity to other diabetes medication in the treatment pathway have limited our ability to fully assess adherence to GLP-1 prescribing. Further research is warranted to better understand general practitioners' prescribing decisions given the cost of prescribing GLP-1 receptor agonists.

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.