Showing papers by "Gordon H. Guyatt published in 2017"

Discrimination and Calibration of Clinical Prediction Models: Users' Guides to the Medical Literature.

Abstract: Accurate information regarding prognosis is fundamental to optimal clinical care. The best approach to assess patient prognosis relies on prediction models that simultaneously consider a number of prognostic factors and provide an estimate of patients' absolute risk of an event. Such prediction models should be characterized by adequately discriminating between patients who will have an event and those who will not and by adequate calibration ensuring accurate prediction of absolute risk. This Users' Guide will help clinicians understand the available metrics for assessing discrimination, calibration, and the relative performance of different prediction models. This article complements existing Users' Guides that address the development and validation of prediction models. Together, these guides will help clinicians to make optimal use of existing prediction models.

Association of Postoperative High-Sensitivity Troponin Levels With Myocardial Injury and 30-Day Mortality Among Patients Undergoing Noncardiac Surgery.

Abstract: Importance Little is known about the relationship between perioperative high-sensitivity troponin T (hsTnT) measurements and 30-day mortality and myocardial injury after noncardiac surgery (MINS). Objective To determine the association between perioperative hsTnT measurements and 30-day mortality and potential diagnostic criteria for MINS (ie, myocardial injury due to ischemia associated with 30-day mortality). Design, Setting, and Participants Prospective cohort study of patients aged 45 years or older who underwent inpatient noncardiac surgery and had a postoperative hsTnT measurement. Starting in October 2008, participants were recruited at 23 centers in 13 countries; follow-up finished in December 2013. Exposures Patients had hsTnT measurements 6 to 12 hours after surgery and daily for 3 days; 40.4% had a preoperative hsTnT measurement. Main Outcomes and Measures A modified Mazumdar approach (an iterative process) was used to determine if there were hsTnT thresholds associated with risk of death and had an adjusted hazard ratio (HR) of 3.0 or higher and a risk of 30-day mortality of 3% or higher. To determine potential diagnostic criteria for MINS, regression analyses ascertained if postoperative hsTnT elevations required an ischemic feature (eg, ischemic symptom or electrocardiography finding) to be associated with 30-day mortality. Results Among 21 842 participants, the mean age was 63.1 (SD, 10.7) years and 49.1% were female. Death within 30 days after surgery occurred in 266 patients (1.2%; 95% CI, 1.1%-1.4%). Multivariable analysis demonstrated that compared with the reference group (peak hsTnT Conclusions and Relevance Among patients undergoing noncardiac surgery, peak postoperative hsTnT during the first 3 days after surgery was significantly associated with 30-day mortality. Elevated postoperative hsTnT without an ischemic feature was also associated with 30-day mortality.

Guideline for opioid therapy and chronic noncancer pain

Abstract: Chronic noncancer pain includes any painful condition that persists for at least three months and is not associated with malignant disease.[1][1] According to seven national surveys conducted between 1994 and 2008, 15%–19% of Canadian adults live with chronic noncancer pain.[2][2] Chronic

2017 American College of Rheumatology Guideline for the Prevention and Treatment of Glucocorticoid-Induced Osteoporosis: ACR GUIDELINE FOR GLUCOCORTICOID-INDUCED OSTEOPOROSIS PREVENTION AND TREATMENT

Abstract: To develop recommendations for prevention and treatment of glucocorticoid‐induced osteoporosis (GIOP).

Approaches to interpreting and choosing the best treatments in network meta-analyses

Abstract: When randomized trials have addressed multiple interventions for the same health problem, network meta-analyses (NMAs) permit researchers to statistically pool data from individual studies including evidence from both direct and indirect comparisons. Grasping the significance of the results of NMAs may be very challenging. Authors may present the findings from such analyses in several numerical and graphical ways. In this paper, we discuss ranking strategies and visual depictions of rank, including the surface under the cumulative ranking (SUCRA) curve method. We present ranking approaches’ merits and limitations and provide an example of how to apply the results of a NMA to clinical practice.

Withholding versus Continuing Angiotensin-converting Enzyme Inhibitors or Angiotensin II Receptor Blockers before Noncardiac Surgery: An Analysis of the Vascular events In noncardiac Surgery patIents cOhort evaluatioN Prospective Cohort.

Abstract: Background:The effect on cardiovascular outcomes of withholding angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers in chronic users before noncardiac surgery is unknown.Methods:In this international prospective cohort study, the authors analyzed data from 14,687 patients (i

Electronic nicotine delivery systems and/or electronic non-nicotine delivery systems for tobacco smoking cessation or reduction: a systematic review and meta-analysis.

Abstract: Objective A systematic review and meta-analysis to investigate the impact of electronic nicotine delivery systems (ENDS) and/or electronic non-nicotine delivery systems (ENNDS) versus no smoking cessation aid, or alternative smoking cessation aids, in cigarette smokers on long-term tobacco use. Data sources Searches of MEDLINE, EMBASE, PsycInfo, CINAHL, CENTRAL and Web of Science up to December 2015. Study selection Randomised controlled trials (RCTs) and prospective cohort studies. Data extraction Three pairs of reviewers independently screened potentially eligible articles, extracted data from included studies on populations, interventions and outcomes and assessed their risk of bias. We used the Grading of Recommendations Assessment, Development and Evaluation approach to rate overall certainty of the evidence by outcome. Data synthesis Three randomised trials including 1007 participants and nine cohorts including 13 115 participants proved eligible. Results provided by only two RCTs suggest a possible increase in tobacco smoking cessation with ENDS in comparison with ENNDS (RR 2.03, 95% CI 0.94 to 4.38; p=0.07; I 2 =0%, risk difference (RD) 64/1000 over 6 to 12 months, low-certainty evidence). Results from cohort studies suggested a possible reduction in quit rates with use of ENDS compared with no use of ENDS (OR 0.74, 95% CI 0.55 to 1.00; p=0.051; I 2 =56%, very low certainty). Conclusions There is very limited evidence regarding the impact of ENDS or ENNDS on tobacco smoking cessation, reduction or adverse effects: data from RCTs are of low certainty and observational studies of very low certainty. The limitations of the cohort studies led us to a rating of very low-certainty evidence from which no credible inferences can be drawn. Lack of usefulness with regard to address the question of e-cigarettes9 efficacy on smoking reduction and cessation was largely due to poor reporting. This review underlines the need to conduct well-designed trials measuring biochemically validated outcomes and adverse effects.

2017 American College of Rheumatology/American Association of Hip and Knee Surgeons Guideline for the Perioperative Management of Antirheumatic Medication in Patients With Rheumatic Diseases Undergoing Elective Total Hip or Total Knee Arthroplasty: ACR/AAHKS GUIDELINE FOR PERIOPERATIVE MANAGEMENT

Abstract: This collaboration between the American College of Rheumatology and the American Association of Hip and Knee Surgeons developed an evidence‐based guideline for the perioperative management of antirheumatic drug therapy for adults with rheumatoid arthritis (RA), spondyloarthritis (SpA) including ankylosing spondylitis and psoriatic arthritis, juvenile idiopathic arthritis (JIA), or systemic lupus erythematosus (SLE) undergoing elective total hip (THA) or total knee arthroplasty (TKA).

Combined Corticosteroid and Antiviral Treatment for Bell Palsy

Abstract: CONTEXT New evidence has emerged regarding the use of corticosteroids and antiviral agents in Bell palsy. OBJECTIVE To estimate the association of corticosteroids and antiviral agents with the risk of unsatisfactory facial recovery in patients with Bell palsy. DATA SOURCES The search included MEDLINE, EMBASE, CENTRAL, PsychInfo, CINAHL, Web of Science, PAPERSFIRST, PROCEEDINGSFIRST, and PROQUEST to identify studies up to March 1, 2009. STUDY SELECTION AND DATA EXTRACTION Eligible studies were randomized controlled trials comparing treatment with either corticosteroids or antiviral agents with a control and measuring at least 1 of the following outcomes: unsatisfactory facial recovery (> or = 4 months), unsatisfactory short-term recovery (6 weeks to < 4 months), synkinesis and autonomic dysfunction, or adverse effects. Two reviewers extracted data on study characteristics, methods, and outcomes. Disagreement was resolved by consensus. RESULTS Eighteen trials involving 2786 patients were eligible. Regression analysis identified a synergistic effect when corticosteroids and antiviral agents were administered in combination compared with alone (odds ratio for interaction term, 0.54 [95% confidence interval {CI}, 0.35-0.83]; P = .004). Meta-analysis using a random-effects model showed corticosteroids alone were associated with a reduced risk of unsatisfactory recovery (relative risk [RR], 0.69 [95% CI, 0.55-0.87]; P = .001) (number needed to treat to benefit 1 person, 11 [95% CI, 8-25]), a reduced risk of synkinesis and autonomic dysfunction (RR, 0.48 [95% CI, 0.36-0.65]; P < .001) (number needed to treat to benefit 1 person, 7 [95% CI, 6-10]), and no increase in adverse effects. Antiviral agents alone were not associated with a reduced risk of unsatisfactory recovery (RR, 1.14 [95% CI, 0.80-1.62]; P = .48). When combined with antiviral agents, corticosteroids were associated with greater benefit (RR, 0.48 [95% CI, 0.29-0.79]; P = .004) than antiviral agents alone. When combined with corticosteroids, antiviral agents were associated with greater risk reduction of borderline significance compared with corticosteroids alone (RR, 0.75 [95% CI, 0.56-1.00]; P = .05). CONCLUSIONS In Bell palsy, corticosteroids are associated with a reduced risk of unsatisfactory recovery. Antiviral agents, when administered with corticosteroids, may be associated with additional benefit.

Knee arthroscopy versus conservative management in patients with degenerative knee disease: a systematic review

Abstract: Objective To determine the effects and complications of arthroscopic surgery compared with conservative management strategies in patients with degenerative knee disease. Design Systematic review. Main outcome measures Pain, function, adverse events. Data sources MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL), Google Scholar and Open Grey up to August 2016. Eligibility criteria For effects, randomised clinical trials (RCTs) comparing arthroscopic surgery with a conservative management strategy (including sham surgery) in patients with degenerative knee disease. For complications, RCTs and observational studies. Review methods Two reviewers independently extracted data and assessed risk of bias for patient-important outcomes. A parallel guideline committee ( BMJ Rapid Recommendations) provided input on the design and interpretation of the systematic review, including selection of patient-important outcomes. We used the GRADE approach to rate the certainty (quality) of the evidence. Results We included 13 RCTs and 12 observational studies. With respect to pain, the review identified high-certainty evidence that knee arthroscopy results in a very small reduction in pain up to 3 months (mean difference =5.4 on a 100-point scale, 95% CI 2.0 to 8.8) and very small or no pain reduction up to 2 years (mean difference =3.1, 95% CI −0.2 to 6.4) when compared with conservative management. With respect to function, the review identified moderate-certainty evidence that knee arthroscopy results in a very small improvement in the short term (mean difference =4.9 on a 100-point scale, 95% CI 1.5 to 8.4) and very small or no improved function up to 2 years (mean difference =3.2, 95% CI −0.5 to 6.8). Alternative presentations of magnitude of effect, and associated sensitivity analyses, were consistent with the findings of the primary analysis. Low-quality evidence suggested a very low probability of serious complications after knee arthroscopy. Conclusions Over the long term, patients who undergo knee arthroscopy versus those who receive conservative management strategies do not have important benefits in pain or function. Trial registration number PROSPERO CRD42016046242.

Adjusted analyses in studies addressing therapy and harm: Users' guides to the medical literature

Abstract: Observational studies almost always have bias because prognostic factors are unequally distributed between patients exposed or not exposed to an intervention. The standard approach to dealing with this problem is adjusted or stratified analysis. Its principle is to use measurement of risk factors to create prognostically homogeneous groups and to combine effect estimates across groups.The purpose of this Users' Guide is to introduce readers to fundamental concepts underlying adjustment as a way of dealing with prognostic imbalance and to the basic principles and relative trustworthiness of various adjustment strategies.One alternative to the standard approach is propensity analysis, in which groups are matched according to the likelihood of membership in exposed or unexposed groups. Propensity methods can deal with multiple prognostic factors, even if there are relatively few patients having outcome events. However, propensity methods do not address other limitations of traditional adjustment: investigators may not have measured all relevant prognostic factors (or not accurately), and unknown factors may bias the results.A second approach, instrumental variable analysis, relies on identifying a variable associated with the likelihood of receiving the intervention but not associated with any prognostic factor or with the outcome (other than through the intervention); this could mimic randomization. However, as with assumptions of other adjustment approaches, it is never certain if an instrumental variable analysis eliminates bias.Although all these approaches can reduce the risk of bias in observational studies, none replace the balance of both known and unknown prognostic factors offered by randomization.

Low intensity pulsed ultrasound for bone healing: systematic review of randomized controlled trials

Abstract: Objective To determine the efficacy of low intensity pulsed ultrasound (LIPUS) for healing of fracture or osteotomy. Design Systematic review and meta-analysis. Data sources Medline, Embase, CINAHL, Cochrane Central Register of Controlled Trials, and trial registries up to November 2016. Study selection Randomized controlled trials of LIPUS compared with sham device or no device in patients with any kind of fracture or osteotomy. Review methods Two independent reviewers identified studies, extracted data, and assessed risk of bias. A parallel guideline committee ( BMJ Rapid Recommendation) provided input on the design and interpretation of the systematic review, including selection of outcomes important to patients. The GRADE system was used to assess the quality of evidence. Results 26 randomized controlled trials with a median sample size of 30 (range 8-501) were included. The most trustworthy evidence came from four trials at low risk of bias that included patients with tibia or clavicle fractures. Compared with control, LIPUS did not reduce time to return to work (percentage difference: 2.7% later with LIPUS, 95% confidence interval 7.7% earlier to 14.3% later; moderate certainty) or the number of subsequent operations (risk ratio 0.80, 95% confidence interval 0.55 to 1.16; moderate certainty). For pain, days to weight bearing, and radiographic healing, effects varied substantially among studies. For all three outcomes, trials at low risk of bias failed to show a benefit with LIPUS, while trials at high risk of bias suggested a benefit (interaction P Conclusions Based on moderate to high quality evidence from studies in patients with fresh fracture, LIPUS does not improve outcomes important to patients and probably has no effect on radiographic bone healing. The applicability to other types of fracture or osteotomy is open to debate. Systematic review registration PROSPERO CRD42016050965

Application of minimal important differences in degenerative knee disease outcomes: a systematic review and case study to inform BMJ Rapid Recommendations

Abstract: Objectives To identify the most credible anchor-based minimal important differences (MIDs) for patient important outcomes in patients with degenerative knee disease, and to inform BMJ Rapid Recommendations for arthroscopic surgery versus conservative management Design Systematic review. Outcome measures Estimates of anchor-based MIDs, and their credibility, for knee symptoms and health-related quality of life (HRQoL). Data sources MEDLINE, EMBASE and PsycINFO. Eligibility criteria We included original studies documenting the development of anchor-based MIDs for patient-reported outcomes (PROs) reported in randomised controlled trials included in the linked systematic review and meta-analysis and judged by the parallel BMJ Rapid Recommendations panel as critically important for informing their recommendation: measures of pain, function and HRQoL. Results 13 studies reported 95 empirically estimated anchor-based MIDs for 8 PRO instruments and/or their subdomains that measure knee pain, function or HRQoL. All studies used a transition rating (global rating of change) as the anchor to ascertain the MID. Among PROs with more than 1 estimated MID, we found wide variation in MID values. Many studies suffered from serious methodological limitations. We identified the following most credible MIDs: Western Ontario and McMaster University Osteoarthritis Index (WOMAC; pain: 12, function: 13), Knee injury and Osteoarthritis Outcome Score (KOOS; pain: 12, activities of daily living: 8) and EuroQol five dimensions Questionnaire (EQ-5D; 0.15). Conclusions We were able to distinguish between more and less credible MID estimates and provide best estimates for key instruments that informed evidence presentation in the associated systematic review and judgements made by the Rapid Recommendation panel. Trial registration number CRD42016047912.

Severity of Hypoxemia and Effect of High-Frequency Oscillatory Ventilation in Acute Respiratory Distress Syndrome

Abstract: Rationale: High-frequency oscillatory ventilation (HFOV) is theoretically beneficial for lung protection, but the results of clinical trials are inconsistent, with study-level meta-analyses suggesting no significant effect on mortality.Objectives: The aim of this individual patient data meta-analysis was to identify acute respiratory distress syndrome (ARDS) patient subgroups with differential outcomes from HFOV.Methods: After a comprehensive search for trials, two reviewers independently identified randomized trials comparing HFOV with conventional ventilation for adults with ARDS. Prespecified effect modifiers were tested using multivariable hierarchical logistic regression models, adjusting for important prognostic factors and clustering effects.Measurements and Main Results: Data from 1,552 patients in four trials were analyzed, applying uniform definitions for study variables and outcomes. Patients had a mean baseline PaO2/FiO2 of 114 ± 39 mm Hg; 40% had severe ARDS (PaO2/FiO2 <100 mm Hg). Mortality ...

Withholding Pantoprazole for Stress Ulcer Prophylaxis in Critically Ill Patients: A Pilot Randomized Clinical Trial and Meta-Analysis.

Abstract: Introduction:A decreased frequency of upper gastrointestinal bleeding and a possible association of proton pump inhibitor use with Clostridium difficile and ventilator-associated pneumonia have raised concerns recently. The Reevaluating the Inhibition of Stress Erosions Pilot Trial determined the fe

The history and development of N-of-1 trials:

Abstract: ‘Trials of therapy’, in which physicians ‘try out’ treatments and assess patients’ responses, are long-established, common elements of routine medical practice. Because ‘trials of therapy’ are usually informal, they may only be reported if treatments are associated with dramatic changes in a patient’s condition – whether by improvement or deterioration. Our understanding of bias suggests that informal ‘trials of therapy’ – comparisons of patients’ condition before and after treatment – do not provide a trustworthy basis for inferring treatment effects. More sophisticated comparisons are usually needed: for example, comparing a patient’s responses when treatments are given or withheld (‘crossed over’) and conducting formal assessment of outcomes. In 1676, Richard Wiseman (a surgeon to King Charles II) reported an unplanned experiment. He had prescribed a pair of laced stockings for a patient suffering from leg oedema. The stockings had reduced the oedema to the extent that the patient ‘was able to walk to his closet, and take the air in his coach, and was well pleased with them’. However, someone suggested to the patient that the stockings might do him harm and persuaded him to remove them. His legs swelled up, he became confined to bed again and developed leg ulcers. Dr Wiseman waited six weeks for the ulcers to heal, restored the laced stockings, with the result that the patient recovered. A century after Wiseman’s crude crossover trial of laced stockings, Caleb Parry, a doctor in Bath, England, published a more formal, planned use of between two and six crossover periods of variable duration in 13 patients, to compare the purgative effects of three varieties of rhubarb. Parry was unable to find any advantage of the more costly Turkish rhubarb compared with English rhubarb. Parry’s ‘trials of therapy’ were important in having used at least two crossovers, but he took no steps to ensure that his andhis patients’ assessments of the treatment effects were not influenced by his or the patients’ knowledgeof the type of rhubarb being given.Fourteen years later, also in Bath, JohnHaygarth compared the effects on rheumatism of a metal ‘tractor’ with a matched wooden (placebo) tractor. This demonstrated that the assumed treatment effects of the metal tractor resulted from patients’ imagination. Haygarth’s study made clear that informal ‘trials of therapy’ can be plagued by false positives (due to placebo effects, physicians’ and patients’ desires to please, the pre-existing expectations of both parties and natural history). And they can also result in false negatives (patients destined to deteriorate and the intervention resulting in them remaining stable). Although more than a century passed after Haygarth before Paul Martini set out principles for designing unbiased crossover trials in his 69-page book, it appears that it was not until 1953 that serious scientific consideration was given to how controlled trials in individual patients could complement traditional parallel group trials. Hogben and Sim recognised that:

Structural valve deterioration after transcatheter aortic valve implantation.

Abstract: Background Transcatheter aortic valve implantation (TAVI), widely used to treat high-risk patients with severe symptomatic aortic stenosis, has recently been extended to younger patients at lower operative risk in whom long-term durability of TAVI devices is an important concern. Therefore, we conducted a systematic review and meta-analysis of observational studies addressing the frequency of structural valve deterioration (SVD) after TAVI. Methods We searched Medline, Embase, Cochrane Database of Systematic Reviews, and Cochrane CENTRAL from 2002 to September 2016. We included observational studies following patients with TAVI for at least 2 years. Independently and in duplicate, we evaluated study eligibility, extracted data, and assessed risk of bias for SVD post-TAVI. Our review used the GRADE system to assess quality of evidence. We pooled incidence rates using a random effects model. Results Thirteen studies including 8914 patients, with a median follow-up between 1.6 and 5 years, reported an incidence of SVD post-TAVI between 0 to 1.34 per 100 patient years. The pooled incidence of SVD was 28.08 per 10 000 patients/year (95% CI 2.46 to 73.44 per 100 patient years). Of those who developed SVD, 12% underwent valve re-intervention. Confidence in the evidence was moderate due to inconsistency among studies. Conclusion Structural valve deterioration is probably an infrequent event within the first 5 years after TAVI. Ascertaining the impact of SVD and the need for valve-related re-interventions to inform recommendations for patients with a longer life-expectancy will require studies including a large number of patients with longer follow-up (>10 years).

Corticosteroids for treatment of sore throat: systematic review and meta-analysis of randomised trials

Abstract: Objective To estimate the benefits and harms of using corticosteroids as an adjunct treatment for sore throat. Design Systematic review and meta-analysis of randomised control trials. Data sources Medline, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), trial registries up to May 2017, reference lists of eligible trials, related reviews. Study selection Randomised controlled trials of the addition of corticosteroids to standard clinical care for patients aged 5 or older in emergency department and primary care settings with clinical signs of acute tonsillitis, pharyngitis, or the clinical syndrome of sore throat. Trials were included irrespective of language or publication status. Review methods Reviewers identified studies, extracted data, and assessed the quality of the evidence, independently and in duplicate. A parallel guideline committee ( BMJ Rapid Recommendation) provided input on the design and interpretation of the systematic review, including the selection of outcomes important to patients. Random effects model was used for meta-analyses. Quality of evidence was assessed with the GRADE approach. Results 10 eligible trials enrolled 1426 individuals. Patients who received single low dose corticosteroids (the most common intervention was oral dexamethasone with a maximum dose of 10 mg) were twice as likely to experience pain relief after 24 hours (relative risk 2.2, 95% confidence interval 1.2 to 4.3; risk difference 12.4%; moderate quality evidence) and 1.5 times more likely to have no pain at 48 hours (1.5, 1.3 to 1.8; risk difference 18.3%; high quality). The mean time to onset of pain relief in patients treated with corticosteroids was 4.8 hours earlier (95% confidence interval −1.9 to −7.8; moderate quality) and the mean time to complete resolution of pain was 11.1 hours earlier (−0.4 to −21.8; low quality) than in those treated with placebo. The absolute pain reduction at 24 hours (visual analogue scale 0-10) was greater in patients treated with corticosteroids (mean difference 1.3, 95% confidence interval 0.7 to 1.9; moderate quality). Nine of the 10 trials sought information regarding adverse events. Six studies reported no adverse effects, and three studies reported few adverse events, which were mostly complications related to disease, with a similar incidence in both groups. Conclusion Single low dose corticosteroids can provide pain relief in patients with sore throat, with no increase in serious adverse effects. Included trials did not assess the potential risks of larger cumulative doses in patients with recurrent episodes of acute sore throat. Systematic review registration PROSPERO CRD42017067808.

Incretin based treatments and mortality in patients with type 2 diabetes: systematic review and meta-analysis

Abstract: Objective To assess the impact of incretin based treatment on all cause mortality in patients with type 2 diabetes. Design Systematic review and meta-analysis of randomised trials. Data sources Medline, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL), and ClinicalTrials.gov. Eligibility criteria Randomised controlled trials that compared glucagon-like peptide-1 (GLP-1) receptor agonists or dipeptidyl peptidase-4 (DPP-4) inhibitors with placebo or active anti-diabetic drugs in patients with type 2 diabetes. Data collection and analysis Paired reviewers independently screened citations, assessed risk of bias of included studies, and extracted data. Peto’s method was used as the primary approach to pool effect estimates from trials, sensitivity analyses were carried out with other statistical approaches, and meta-regression was applied for six prespecified hypotheses to explore heterogeneity. The GRADE approach was used to rate the quality of evidence. Results 189 randomised controlled trials (n=155 145) were included, all of which were at low to moderate risk of bias; 77 reported no events of death and 112 reported 3888 deaths among 151 614 patients. Meta-analysis of 189 trials showed no difference in all cause mortality between incretin drugs versus control (1925/84 136 v 1963/67 478; odds ratio 0.96, 95% confidence interval 0.90 to 1.02, I 2 =0%; risk difference 3 fewer events (95% confidence interval 7 fewer to 1 more) per 1000 patients over five years; moderate quality evidence). Results suggested the possibility of a mortality benefit with GLP-1 agonists but not DPP-4 inhibitors, but the subgroup hypothesis had low credibility. Sensitivity analyses showed no important differences in the estimates of effects. Conclusions Current evidence does not support the suggestion that incretin based treatment increases all cause mortality in patients with type 2 diabetes. Further studies are warranted to examine if the effect differs between GLP-1 agonists versus DPP-4 inhibitors.