Objective:To compare the benefits and harms of drug treatments for adults with type 2 diabetes, adding non-steroidal mineralocorticoid receptor antagonists (including finerenone) and tirzepatide (a dual glucose dependent insulinotropic polypeptide (GIP)/glucagon-like peptide-1 (GLP-1) receptor agonist) to previously existing treatment options. Design:Systematic review and network meta-analysis. Data sources:Ovid Medline, Embase, and Cochrane Central up to 14 October 2022. Eligibility criteria for selecting studies:Eligible randomised controlled trials compared drugs of interest in adults with type 2 diabetes. Eligible trials had a follow-up of 24 weeks or longer. Trials systematically comparing combinations of more than one drug treatment class with no drug, subgroup analyses of randomised controlled trials, and non-English language studies were deemed ineligible. Certainty of evidence was assessed following the GRADE (grading of recommendations, assessment, development and evaluation) approach. Results:The analysis identified 816 trials with 471 038 patients, together evaluating 13 different drug classes; all subsequent estimates refer to the comparison with standard treatments. Sodium glucose cotransporter-2 (SGLT-2) inhibitors (odds ratio 0.88, 95% confidence interval 0.83 to 0.94; high certainty) and GLP-1 receptor agonists (0.88, 0.82 to 0.93; high certainty) reduce all cause death; non-steroidal mineralocorticoid receptor antagonists, so far tested only with finerenone in patients with chronic kidney disease, probably reduce mortality (0.89, 0.79 to 1.00; moderate certainty); other drugs may not. The study confirmed the benefits of SGLT-2 inhibitors and GLP-1 receptor agonists in reducing cardiovascular death, non-fatal myocardial infarction, admission to hospital for heart failure, and end stage kidney disease. Finerenone probably reduces admissions to hospital for heart failure and end stage kidney disease, and possibly cardiovascular death. Only GLP-1 receptor agonists reduce non-fatal stroke; SGLT-2 inhibitors are superior to other drugs in reducing end stage kidney disease. GLP-1 receptor agonists and probably SGLT-2 inhibitors and tirzepatide improve quality of life. Reported harms were largely specific to drug class (eg, genital infections with SGLT-2 inhibitors, severe gastrointestinal adverse events with tirzepatide and GLP-1 receptor agonists, hyperkalaemia leading to admission to hospital with finerenone). Tirzepatide probably results in the largest reduction in body weight (mean difference -8.57 kg; moderate certainty). Basal insulin (mean difference 2.15 kg; moderate certainty) and thiazolidinediones (mean difference 2.81 kg; moderate certainty) probably result in the largest increases in body weight. Absolute benefits of SGLT-2 inhibitors, GLP-1 receptor agonists, and finerenone vary in people with type 2 diabetes, depending on baseline risks for cardiovascular and kidney outcomes (https://matchit.magicevidence.org/230125dist-diabetes). Conclusions:This network meta-analysis extends knowledge beyond confirming the substantial benefits with the use of SGLT-2 inhibitors and GLP-1 receptor agonists in reducing adverse cardiovascular and kidney outcomes and death by adding information on finerenone and tirzepatide. These findings highlight the need for continuous assessment of scientific progress to introduce cutting edge updates in clinical practice guidelines for people with type 2 diabetes.

There has not been a clear answer about the efficacy of intraoperative radiotherapy (IORT) for women with early-stage breast cancer.The aim of this meta-analysis was to summarize the available evidence comparing the efficacy and safety of IORT with those of whole-breast external beam radiotherapy (EBRT) for women with early-stage breast cancer.MEDLINE, EMBASE, the Web of Science, and the Cochrane Library were searched up to October 2014. Two authors independently conducted the literature selection and data extraction.Studies that compared IORT with whole-breast EBRT were included in the systematic review. IORT was defined as a single dose of irradiation to the tumor bed during breast-conserving surgery rather than whole-breast irradiation.Qualities of RCTs were evaluated according to the PEDro scale. Qualities of non-RCTs were evaluated according to the Methodological Index for Non-Randomized Studies (MINORS). The risk ratios (RRs) of ipsilateral breast tumor recurrence, overall mortality, breast cancer mortality, non-breast cancer mortality, and distant metastasis were pooled using a random-effects model.Four studies with 5415 patients were included in this meta-analysis, including 2 randomized controlled trials (RCTs) and 2 non-RCTs. Ipsilateral breast tumor recurrence was significantly higher in patients with IORT compared to those with whole-breast EBRT (RR 2.83, 95% CI 1.23-6.51), but with significant heterogeneity (I = 58.5%, P = 0.065). Comparing IORT with whole-breast EBRT, the pooled RRs for overall mortality, breast cancer mortality, non-breast cancer mortality, and distant metastasis were 0.88 (95% CI: 0.66-1.17), 1.20 (95% CI: 0.77-1.86), 0.76 (95% CI: 0.44-1.31), and 0.95 (95% CI: 0.61-1.49), respectively.IORT had a significantly higher risk of ipsilateral breast tumor recurrence than whole-breast EBRT. Overall mortality did not differ significantly. IORT should be used in conjunction with the prudent selection of suitable patients. It is imperative to identify women with a low risk of local recurrence