Objective To evaluate sodium-glucose cotransporter-2 (SGLT-2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists in patients with type 2 diabetes at varying cardiovascular and renal risk. Design Network meta-analysis. Data sources Medline, Embase, and Cochrane CENTRAL up to 11 August 2020. Eligibility criteria for selecting studies Randomised controlled trials comparing SGLT-2 inhibitors or GLP-1 receptor agonists with placebo, standard care, or other glucose lowering treatment in adults with type 2 diabetes with follow up of 24 weeks or longer. Studies were screened independently by two reviewers for eligibility, extracted data, and assessed risk of bias. Main outcome measures Frequentist random effects network meta-analysis was carried out and GRADE (grading of recommendations assessment, development, and evaluation) used to assess evidence certainty. Results included estimated absolute effects of treatment per 1000 patients treated for five years for patients at very low risk (no cardiovascular risk factors), low risk (three or more cardiovascular risk factors), moderate risk (cardiovascular disease), high risk (chronic kidney disease), and very high risk (cardiovascular disease and kidney disease). A guideline panel provided oversight of the systematic review. Results 764 trials including 421 346 patients proved eligible. All results refer to the addition of SGLT-2 inhibitors and GLP-1 receptor agonists to existing diabetes treatment. Both classes of drugs lowered all cause mortality, cardiovascular mortality, non-fatal myocardial infarction, and kidney failure (high certainty evidence). Notable differences were found between the two agents: SGLT-2 inhibitors reduced mortality and admission to hospital for heart failure more than GLP-1 receptor agonists, and GLP-1 receptor agonists reduced non-fatal stroke more than SGLT-2 inhibitors (which appeared to have no effect). SGLT-2 inhibitors caused genital infection (high certainty), whereas GLP-1 receptor agonists might cause severe gastrointestinal events (low certainty). Low certainty evidence suggested that SGLT-2 inhibitors and GLP-1 receptor agonists might lower body weight. Little or no evidence was found for the effect of SGLT-2 inhibitors or GLP-1 receptor agonists on limb amputation, blindness, eye disease, neuropathic pain, or health related quality of life. The absolute benefits of these drugs vary substantially across patients from low to very high risk of cardiovascular and renal outcomes (eg, SGLT-2 inhibitors resulted in 5 to 48 fewer deaths in 1000 patients over five years; see interactive decision support tool ( https://magicevidence.org/match-it/200820dist/#!/ ) for all outcomes. Conclusions In patients with type 2 diabetes, SGLT-2 inhibitors and GLP-1 receptor agonists reduced cardiovascular and renal outcomes, with notable differences in benefits and harms. Absolute benefits are determined by individual risk profiles of patients, with clear implications for clinical practice, as reflected in the BMJ Rapid Recommendations directly informed by this systematic review. Systematic review registration PROSPERO CRD42019153180.

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Osteoporotic vertebral compression fractures (VCFs) are a risk factor for morbidity and mortality, frequently asymptomatic and often present in computed tomography (CT) scans performed for unrelated conditions. Computer‐aided diagnosis (CAD) of VCF from such images can potentially improve identification and treatment of osteoporosis. This single‐blinded, single tertiary center study compared a CAD (Zebra Medical Vision®) to an adjudicated imaging specialist reevaluation using a retrospective consecutive sample of abdominal and thoracic CT scans (n = 2357) performed as part of routine care. Subjects over 50 years between January 1, 2019 and May 12, 2019 were included. Duplicates and unanalyzable scans were excluded resulting in a total of 1696 CT scans. The sensitivity, specificity, and accuracy were calculated for all VCF and for Genant grades 2 or 3 (ie, height loss of >25%) using imaging specialist as the gold standard. Prestudy VCF reporting by hospital‐rostered radiologist was used to calculate the number of scans needed to screen (NNS) to detect one additional VCF using CAD. Prevalence of any VCF was 24% (406/1696) and of Genant 2/3 VCF was 18% (280/1570). The sensitivity and specificity were 54% and 92%, for all fractures, respectively, and 65% and 92% for Genant 2/3 fractures, respectively. Accuracy for any VCF, and for detection of Genant 2/3 VCF, was 83% and 88%, respectively. Of 221 CAD‐detected VCFs, 133 (60.2%) were reported prestudy resulting in 88 additional fractures (72 Genant 2/3) being identified by CAD. NNS to detect one additional VCF was 19 scans for all fractures and 23 for Genant 2/3 fractures. Thus, the CAD tested in this study had a high specificity with moderate sensitivity to detect incidental vertebral fractures in CT scans performed for routine care. A low NNS suggests it is an efficient tool to assist radiologists and clinicians to improve detection and reporting of vertebral fractures. © 2020 American Society for Bone and Mineral Research (ASBMR).