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ObjectiveTo evaluate the efficacy and safety of artificial pancreas treatment in non-pregnant outpatients with type 1 diabetes.DesignSystematic review and meta-analysis of randomised controlled trials.Data sourcesMedline, Embase, Cochrane Library, and grey literature up to 2 February 2018.Eligibility criteria for selecting studiesRandomised controlled trials in non-pregnant outpatients with type 1 diabetes that compared the use of any artificial pancreas system with any type of insulin based treatment. Primary outcome was proportion (%) of time that sensor glucose level was within the near normoglycaemic range (3.9-10 mmol/L). Secondary outcomes included proportion (%) of time that sensor glucose level was above 10 mmol/L or below 3.9 mmol/L, low blood glucose index overnight, mean sensor glucose level, total daily insulin needs, and glycated haemoglobin. The Cochrane Collaboration risk of bias tool was used to assess study quality.Results40 studies (1027 participants with data for 44 comparisons) were included in the meta-analysis. 35 comparisons assessed a single hormone artificial pancreas system, whereas nine comparisons assessed a dual hormone system. Only nine studies were at low risk of bias. Proportion of time in the near normoglycaemic range (3.9-10.0 mmol/L) was significantly higher with artificial pancreas use, both overnight (weighted mean difference 15.15%, 95% confidence interval 12.21% to 18.09%) and over a 24 hour period (9.62%, 7.54% to 11.7%). Artificial pancreas systems had a favourable effect on the proportion of time with sensor glucose level above 10 mmol/L (−8.52%, −11.14% to −5.9%) or below 3.9 mmol/L (−1.49%, −1.86% to −1.11%) over 24 hours, compared with control treatment. Robustness of findings for the primary outcome was verified in sensitivity analyses, by including only trials at low risk of bias (11.64%, 9.1% to 14.18%) or trials under unsupervised, normal living conditions (10.42%, 8.63% to 12.2%). Results were consistent in a subgroup analysis both for single hormone and dual hormone artificial pancreas systems.ConclusionsArtificial pancreas systems are an efficacious and safe approach for treating outpatients with type 1 diabetes. The main limitations of current research evidence on artificial pancreas systems are related to inconsistency in outcome reporting, small sample size, and short follow-up duration of individual trials.

Empagliflozin effectively lowers blood glucose and provides additional clinical benefits including body weight and blood pressure reduction. Ongoing trials will elucidate the long-term safety and effect of empagliflozin on cardiovascular outcomes.

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This article has an accompanying continuing medical education activity, also eligible for MOC credit, on page e109. Learning Objective-Upon completion of this activity, successful learners will be able to identify the appropriate test for screening and surveillance for esophageal varices in patients with compensated advanced chronic liver disease (cACLD). BACKGROUND & AIMS:We aimed to assess the accuracy of Baveno VI criteria for identification of high-risk varices (HRVs) and varices of any size in patients with compensated advanced chronic liver disease (cACLD). METHODS:We performed a systematic search of publications through December 2018 for studies that assessed the accuracy of Baveno VI criteria for screening for varices in patients with cACLD. We used hierarchical models to synthesize evidence. We also conducted a post hoc analysis to assess the accuracy of Expanded Baveno VI criteria. We appraised the confidence in estimates using the Grading of Recommendations Assessment, Development and Evaluation approach. RESULTS:We identified 30 studies (8469 participants). Pooled values of Baveno VI criteria for HRVs (26 studies) were a sensitivity of 0.97 (95% CI, 0.95-0.98) and a specificity of 0.32 (95% CI, 0.26-0.39). Pooled sensitivity of Expanded Baveno VI criteria for HRVs (12 studies) was 0.90 (95% CI, 0.85-0.93) and specificity was 0.51 (95% CI, 0.45-0.57). In 1000 patients with cACLD, with a prevalence of HRVs of 20%, Baveno VI criteria would prevent endoscopy in 262 patients, but 6 patients with HRVs would be missed. Instead, use of the Expanded Baveno VI criteria would result in 428 patients avoiding endoscopy, but 20 patients with HRVs would be missed. The credibility of our findings is moderate or low, mainly owing to the retrospective design of most studies. CONCLUSIONS:Baveno VI criteria have high diagnostic accuracy as a triage test for screening for HRVs in patients with cACLD. Expanded Baveno VI criteria could reduce the proportion of unnecessary endoscopies further, nevertheless with a higher rate of missed HRVs.

Aims/hypothesis Tirzepatide is a novel dual glucose-dependent insulinotropic peptide (GIP) and glucagon-like peptide-1 receptor agonist (GLP-1 RA) currently under review for marketing approval. Individual trials have assessed the clinical profile of tirzepatide vs different comparators. We conducted a systematic review and meta-analysis to assess the efficacy and safety of tirzepatide for type 2 diabetes. Methods We searched PubMed, Embase, Cochrane and ClinicalTrials.gov up until 27 October 2021 for randomised controlled trials with a duration of at least 12 weeks that compared once-weekly tirzepatide 5, 10 or 15 mg with placebo or other glucose-lowering drugs in adults with type 2 diabetes irrespective of their background glucose-lowering treatment. The primary outcome was change in HbA1c from baseline. Secondary efficacy outcomes included change in body weight, proportion of individuals reaching the HbA1c target of <53 mmol/mol (<7.0%), ≤48 mmol/mol (≤6.5%) or <39 mmol/mol (<5.7%), and proportion of individuals with body weight loss of at least 5%, 10% or 15%. Safety outcomes included hypoglycaemia, gastrointestinal adverse events, treatment discontinuation due to adverse events, serious adverse events, and mortality. We used version 2 of the Cochrane risk-of-bias tool for randomised trials to assess risk of bias for the primary outcome. Results Seven trials (6609 participants) were included. A dose-dependent superiority in lowering HbA1c was evident with all three tirzepatide doses vs all comparators, with mean differences ranging from −17.71 mmol/mol (−1.62%) to −22.35 mmol/mol (−2.06%) vs placebo, −3.22 mmol/mol (−0.29%) to −10.06 mmol/mol (−0.92%) vs GLP-1 RAs, and −7.66 mmol/mol (−0.70%) to −12.02 mmol/mol (−1.09%) vs basal insulin regimens. Tirzepatide was more efficacious in reducing body weight; reductions vs GLP-1 RAs ranged from 1.68 kg with tirzepatide 5 mg to 7.16 kg with tirzepatide 15 mg. Incidence of hypoglycaemia with tirzepatide was similar vs placebo and lower vs basal insulin. Nausea was more frequent with tirzepatide vs placebo, especially with tirzepatide 15 mg (OR 5.60 [95% CI 3.12, 10.06]), associated with higher incidence of vomiting (OR 5.50 [95% CI 2.40, 12.59]) and diarrhoea (OR 3.31 [95% CI 1.40, 7.85]). Odds of gastrointestinal events were similar between tirzepatide and GLP-1 RAs, except for diarrhoea with tirzepatide 10 mg (OR 1.51 [95% CI 1.07, 2.15]). Tirzepatide 15 mg led to higher discontinuation rate of study medication due to adverse events regardless of comparator, while all tirzepatide doses were safe in terms of serious adverse events and mortality. Conclusions/interpretation A dose-dependent superiority on glycaemic efficacy and body weight reduction was evident with tirzepatide vs placebo, GLP-1 RAs and basal insulin. Tirzepatide did not increase the odds of hypoglycaemia but was associated with increased incidence of gastrointestinal adverse events. Study limitations include presence of statistical heterogeneity in the meta-analyses for change in HbA1c and body weight, assessment of risk of bias solely for the primary outcome, and generalisation of findings mainly to individuals who are overweight or obese and already on metformin-based background therapy. PROSPERO registration no. CRD42021283449. Graphical abstract

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