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Aim: To conduct a meta‐analysis of cardiovascular outcome trials on the effects of glucagon‐like peptide‐1 receptor agonists (GLP‐1RAs) on major adverse cardiovascular events (MACE). Methods: A search of MEDLINE, EMBASE, Cochrane database and clinicaltrials.gov was performed to identify controlled trials (up to 15 June 2019) of GLP‐1RAs with a cardiovascular endpoint. The principal endpoint of the present meta‐analysis was MACE; secondary endpoints included myocardial infarction, stroke, cardiovascular and all‐cause mortality, and hospitalization for heart failure. Mantel–Haenszel odds ratios (MH‐ORs) with 95% confidence intervals (CIs) were calculated for all outcomes. Results: In the seven trials included, all placebo‐controlled, GLP‐1RA treatment was associated with a reduction in MACE (MH‐OR 0.87 [95% CI 0.81, 0.93]). Cardiovascular and all‐cause mortality, myocardial infarction and stroke were also reduced (MH‐OR 0.88 [95% CI 0.80, 0.96], MH‐OR 0.90 [95% CI 0.82, 0.98], MH‐OR 0.91 [95% CI 0.84, 0.98] and MH‐OR 0.86 [95% CI 0.77, 0.97], respectively). Results for hospitalization for heart failure were not statistically significant (MH‐OR 0.93 [95% CI 0.83, 1.04]). The meta‐analyses of patient subgroups showed a significant reduction in MACE with GLP‐1RAs, irrespective of gender, advanced age and obesity. Conclusions: GLP‐1RAs are associated with a reduction in cardiovascular morbidity and mortality in high‐risk patients with diabetes. This effect does not appear to be moderated by gender or body mass index. The possibility of different effects of GLP‐1RAs between patients in primary and secondary prevention merits further investigation. [ABSTRACT FROM AUTHOR]

Aim: The aim of this meta‐analysis of randomized trials was to assess the effects of SGLT‐2i on the overall incidence of malignancies and on different types of cancer, summerizing the results of trials with a duration of at least 1 year. This was done in light of the effect of SGLT‐2 inhibitors (SGLT‐2is) that has been highlighted by some studies, showing an increased incidence of bladder cancer, particularly with use of empagliflozin. Materials and methods: A Medline and Embase search for "Canaglifozin", "Dapaglifozin", "Empaglifozin", "Ertuglifozin", "Ipraglifozin", Tofoglifozin" or "Luseoglifozin" was performed, identifying randomized trials with a duration of more than 52 weeks up to 1 December 2018 that compared SGLT‐2is with placebo or active comparators. The outcomes considered were all types of cancer and several site‐specific cancers (ie, breast, pulmonary, gastrointestinal, hepatic, pancreatic, skin, prostate and bladder). Mantel–Haenszel odds ratios with 95% Confidence Intervals (MH‐OR, 95% CI) were calculated for all outcomes. Results: A total of 27 trials fulfilled the inclusion criteria. Retrieved trials had enrolled 27 744 and 20 441 patients in SGLT‐2 inhibitor and comparator groups, respectively. No difference was observed in the incidence of all malignancies between patients allocated to SGLT‐2i and comparators (MH‐OR 0.98[0.77–1.24]). The incidence of bladder cancer, and of any other type of cancer, was not significantly increased by treatment with any SGLT‐2i. Conclusions: Available data from randomized trials do not suggest a detrimental effect of SGLT‐2is on the incidence of malignancies in general, or in bladder cancer in particular. [ABSTRACT FROM AUTHOR]

Aims: Sodium glucose co‐transport‐2 (SGLT‐2) inhibitors reduce tubular glucose reabsorption, producing a reduction of blood glucose without stimulating insulin release. The aim of this meta‐analysis was the systematic collection of available data from randomized trials, in order to establish the durability of the efficacy of SGLT‐2 inhibitors on glycaemic control and body mass index. Methods: A meta‐analysis was performed, including all trials with a duration of at least 12 weeks, comparing SGLT‐2 inhibitors with non‐SGLT‐2 inhibitor agents in type 2 diabetes. The principal outcome was the effect of SGLT‐2 inhibitors on hemoglobin A1c (HbA1c) at 12, 24, 52 and 104 weeks. Data on body mass index at the same time points were also collected. Results: Among 66 randomized trials, HbA1c reduction at 12, 24, 52 and 104 weeks was 0.63% (0.57; 0.68, 0.63% (0.57; 0.70), 0.66% (0.57; 0.74) and 0.60% (0.40; 0.81), respectively. SGLT‐2 inhibitors showed a greater efficacy than dipeptidyl‐peptidase‐4 inhibitors (DPP‐4i). Sulfonylureas appeared to be superior to SGLT‐2 inhibitors at 12 weeks, but not at 24 and 52 weeks; SGLT‐2 inhibitors produced a greater reduction in HbA1c than did sulfonylureas at 104 weeks. SGLT‐2 inhibitor‐induced weight loss in placebo‐controlled trials appeared to increase progressively with the duration of treatment. Conclusions: SGLT‐2 inhibitors showed a good persistence of efficacy, at least up to 2 years, with a small but significant superiority over DPP‐4i. Sulfonylureas are more effective in the very short term, but less effective in the longer term. [ABSTRACT FROM AUTHOR]

Aim Glucagon-like peptide 1 receptor agonists ( GLP1-RA) have been associated with an increased risk of pancreatitis and pancreatic cancer. Prior meta-analyses of randomized controlled trials failed to show any significant increase of risk; however, those meta-analyses did not include the recently published cardiovascular outcome trials ( CVOT) with GLP1-RA, which provide a substantial additional body of data. The aim of the present meta-analysis is to assess the effect of GLP1-RA on pancreatitis, pancreatic cancers and cholelithiasis. Materials and methods A Medline search for GLP-1 receptor agonists (exenatide, liraglutide, lixisenatide, albiglutide, dulaglutide or semaglutide) was performed, collecting all randomized clinical trials with a duration >11 weeks, enrolling patients with type 2 diabetes and comparing a GLP-1 receptor agonist with placebo or any other non- GLP-1 receptor agonist drug. Results Of the 113 trials fulfilling inclusion criteria, 13 did not report information on pancreatitis, whereas 72 reported no events in all treatment groups. The incidence of pancreatitis and pancreatic cancer with GLP1-RA was not significantly different from that observed in comparator arms ( MH-OR [95% CI] 0.93 [0.65-1.34], P = .71, and 0.94 [0.52-1.70], P = .84, respectively), whereas, a significantly increased risk of cholelithiasis ( MH-OR [95% CI] 1.30 [1.01-1.68], P = .041) was detected. Conclusions Presently available data confirm the safety of GLP-1 receptor agonists for pancreatitis. Conversely, therapy with those drugs is associated with an increased risk of cholelithiasis, which deserves further investigation. [ABSTRACT FROM AUTHOR]