{
  "abstract": "Abstract Objective To provide up-to-date evidence on key benefits, harms, and uncertainties regarding medications for adults with type 2 diabetes.Design Living systematic review and network meta-analysis (NMA), using frequentist random effects and GRADE (grading of recommendations, assessment, development and evaluation) approaches. Updates are planned at least two times a year.Data sources Medline and Embase, searched up to 31 July 2024 for the current iteration.Study selection Randomised controlled trials of at least 24 weeks comparing one or more medications with standard treatment, placebo, or each other.Results The systematic review and NMA includes 493 168 participants from 869 trials (adding 53 trials since October 2022) reporting data for 13 drug classes (63 drugs) and 26 outcomes of interest. Regarding benefits, moderate to high certainty evidence confirms the well established cardiovascular and kidney benefits of sodium-glucose cotransporter-2 (SGLT-2) inhibitors, glucagon-like peptide-1 receptor agonists (GLP-1RAs), and finerenone (the last for patients with established chronic kidney disease). The most effective drugs in reducing body weight were tirzepatide (mean difference (MD) −8.63 kg (95% confidence interval −9.34 to −7.93); moderate certainty) and orforglipron (MD −7.87 kg (−10.24 to −5.50); low certainty), followed by eight other GLP-1RAs (high to moderate certainty). Absolute benefits of medications vary substantially depending on the baseline risk of cardiovascular and kidney outcomes; risk-stratified absolute effects of medications are summarised using an interactive multiple comparisons tool ( https://matchit.magicevidence.org/250709dist-diabetes/#!/). Regarding medication-specific harms, SGLT-2 inhibitors increase genital infections (odds ratio (OR) 3.29 (95% CI 2.88 to 3.77); high certainty) and ketoacidosis due to diabetes (OR 2.08 (1.45 to 2.99); high certainty), and probably increase amputations (OR 1.27 (1.01 to 1.61); moderate certainty); tirzepatide and GLP-1RAs probably increase severe gastrointestinal events (most increased risk with tirzepatide (OR 4.21 (1.87 to 9.49); moderate certainty)); finerenone increases severe hyperkalaemia (OR 5.92 (3.02 to 11.62); high certainty); and thiazolidinediones increase major osteoporotic fractures and probably increase hospitalisation for heart failure. Sulfonylureas, insulin, and dipeptidyl peptidase-4 inhibitors probably increase the risk of severe hypoglycaemia. There is low to very low certainty evidence for effects on other diabetes-related complications, including neuropathy and visual impairment. Despite interest in the issue, there is uncertainty about whether GLP-1RAs may reduce dementia (OR 0.92 (0.83 to 1.02); low certainty).Conclusions This living systematic review provides a comprehensive summary of the cardiovascular, kidney, and weight loss benefits, as well as medication-specific harms of medications for adults with type 2 diabetes, including effects of SGLT-2 inhibitors, GLP-1RAs, finerenone and tirzepatide.Systematic review registration PROSPERO number: CRD42022325948. A more detailed protocol is available at https://data.aliveevidence.org/records/q02rv-km486.Readers’ notes This article is the first version of a living systematic review. It is linked to a living BMJ Rapid Recommendation and other living clinical practice guidelines, presenting risk stratified recommendations for patients with type 2 diabetes at lower, moderate, and higher risk of cardiovascular and kidney complications. The latest evidence will be made available via the BMJ Rapid Recommendation and via an interactive GRADE evidence summary (MATCH-IT: https://matchit.magicevidence.org/250709dist-diabetes/#!/). Major updates will be published in The BMJ.",
  "authors": [
    {
      "affiliations": [
        "Department of Endocrinology and Metabolism, Laboratory of Diabetes and Metabolism Research, West China Hospital, Sichuan University, Chengdu, 610041, China",
        "MAGIC China Centre, Cochrane China Centre, Chinese Evidence-based Medicine, West China Hospital, Sichuan University, Chengdu, 610041, China",
        "co-first authors who contribute equally to this study"
      ],
      "name": "Kailei Nong"
    },
    {
      "affiliations": [
        "Future Evidence Foundation, Melbourne, Australia",
        "School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia",
        "co-first authors who contribute equally to this study"
      ],
      "name": "Britta Tendal Jeppesen"
    },
    {
      "affiliations": [
        "Groningen Research Institute of Pharmacy, Faculty of Science and Engineering, University of Groningen, Groningen, The Netherlands",
        "co-first authors who contribute equally to this study"
      ],
      "name": "Qingyang Shi"
    },
    {
      "affiliations": [
        "Department of Health Research Methods, Evidence and Impact, McMaster University, ON, Canada",
        "Division of General Internal Medicine, Division of Clinical Epidemiology, University Hospitals of Geneva, Geneva, Switzerland",
        "MAGIC Evidence Ecosystem Foundation, Oslo, Norway"
      ],
      "name": "Thomas Agoritsas"
    },
    {
      "affiliations": [
        "Department of Health Research Methods, Evidence and Impact, McMaster University, ON, Canada",
        "MAGIC Evidence Ecosystem Foundation, Oslo, Norway"
      ],
      "name": "Gordon H Guyatt"
    },
    {
      "affiliations": [
        "Australian Living Evidence Collaboration (ALEC), Cochrane Australia, School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia"
      ],
      "name": "Heath White"
    },
    {
      "affiliations": [
        "Department of Endocrinology and Metabolism, Laboratory of Diabetes and Metabolism Research, West China Hospital, Sichuan University, Chengdu, 610041, China",
        "MAGIC China Centre, Cochrane China Centre, Chinese Evidence-based Medicine, West China Hospital, Sichuan University, Chengdu, 610041, China"
      ],
      "name": "Yiyuan Gao"
    },
    {
      "affiliations": [
        "Department of Health Research Methods, Evidence and Impact, McMaster University, ON, Canada",
        "MAGIC Evidence Ecosystem Foundation, Oslo, Norway",
        "Division of General Internal Medicine, University of Alberta, Edmonton, Alberta, Canada"
      ],
      "name": "Arnav Agarwal"
    },
    {
      "affiliations": [
        "BMJ Editorial Tavistock Square, London, UK"
      ],
      "name": "Helen Macdonald"
    },
    {
      "affiliations": [
        "Department of Endocrinology and Metabolism, Laboratory of Diabetes and Metabolism Research, West China Hospital, Sichuan University, Chengdu, 610041, China",
        "MAGIC China Centre, Cochrane China Centre, Chinese Evidence-based Medicine, West China Hospital, Sichuan University, Chengdu, 610041, China"
      ],
      "name": "Xinyu Zou"
    },
    {
      "affiliations": [
        "Australian Living Evidence Collaboration (ALEC), Cochrane Australia, School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia",
        "Australian Diabetes Society, Sydney, Australia"
      ],
      "name": "Tanya Millard"
    },
    {
      "affiliations": [
        "Forschergruppe Diabetes eV at the Helmholtz Centre, Munich-Neuherberg, Germany"
      ],
      "name": "Oliver Schnell"
    },
    {
      "affiliations": [
        "Clinic for Cardiology, Angiology, and Intensive Care Medicine, RWTH Aachen University, University Hospital Aachen, Aachen, Germany"
      ],
      "name": "Nikolaus Marx"
    },
    {
      "affiliations": [
        "Division of Nephrology, University of Arizona College of Medicine Tucson, Tucson, AZ, USA"
      ],
      "name": "Frank C Brosius III"
    },
    {
      "affiliations": [
        "Australian Living Evidence Collaboration (ALEC), Cochrane Australia, School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia"
      ],
      "name": "Steve McDonald"
    },
    {
      "affiliations": [
        "Australian Living Evidence Collaboration (ALEC), Cochrane Australia, School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia"
      ],
      "name": "Matthew Quigley"
    },
    {
      "affiliations": [
        "Healthcare Innovation Research Laboratory, Nursing Key Laboratory of Sichuan Province, National Clinical Research Centre for Geriatrics, West China Hospital, Sichuan University/West China School of Nursing, Sichuan University, Chengdu, China"
      ],
      "name": "Xin Tian"
    },
    {
      "affiliations": [
        "Department of Endocrinology and Metabolism, Laboratory of Diabetes and Metabolism Research, West China Hospital, Sichuan University, Chengdu, 610041, China",
        "MAGIC China Centre, Cochrane China Centre, Chinese Evidence-based Medicine, West China Hospital, Sichuan University, Chengdu, 610041, China"
      ],
      "name": "Qinlin Fan"
    },
    {
      "affiliations": [
        "Australian Diabetes Society, Sydney, Australia"
      ],
      "name": "Barbara White"
    },
    {
      "affiliations": [
        "Department of Orthopaedics, Orthopaedic Research Institute, West China Hospital, Sichuan University, Chengdu, China"
      ],
      "name": "Yunhe Mao"
    },
    {
      "affiliations": [
        "Department of Endocrinology and Metabolism, Laboratory of Diabetes and Metabolism Research, West China Hospital, Sichuan University, Chengdu, 610041, China"
      ],
      "name": "Xiaohui Pan"
    },
    {
      "affiliations": [
        "Center of Infectious Diseases, West China Hospital, Sichuan University, Chengdu, China",
        "Division of Infectious Diseases, State Key Laboratory of Biotherapy and Centre of Infectious Disease, West China Hospital, Sichuan University, Chengdu, China"
      ],
      "name": "Changhai Liu"
    },
    {
      "affiliations": [
        "Department of Cardiology, Shandong Provincial Hospital affiliated to Shandong First Medical University, Jinan, China"
      ],
      "name": "Chunjuan Zhai"
    },
    {
      "affiliations": [
        "Department of Paediatric Surgery, West China Hospital, Sichuan University, Chengdu, China"
      ],
      "name": "Chi Yuan"
    },
    {
      "affiliations": [
        "Department of Hypertension and Endocrinology, Daping Hospital, Centre for Hypertension and Metabolic Diseases, Army Medical University of PLA, Chongqing Institute of Hypertension, Chongqing, China"
      ],
      "name": "Qiang Li"
    },
    {
      "affiliations": [
        "Department of Endocrinology and Metabolism, Laboratory of Diabetes and Metabolism Research, West China Hospital, Sichuan University, Chengdu, 610041, China",
        "MAGIC China Centre, Cochrane China Centre, Chinese Evidence-based Medicine, West China Hospital, Sichuan University, Chengdu, 610041, China"
      ],
      "name": "Jing An"
    },
    {
      "affiliations": [
        "Department of Anaesthesiology, Laboratory of Anaesthesia and Critical Care Medicine, National-Local Joint Engineering Research Centre of Translational Medicine of Anaesthesiology, Frontiers Science Centre for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, China"
      ],
      "name": "Yu Gan"
    },
    {
      "affiliations": [
        "Healthcare Innovation Research Laboratory, Nursing Key Laboratory of Sichuan Province, National Clinical Research Centre for Geriatrics, West China Hospital, Sichuan University/West China School of Nursing, Sichuan University, Chengdu, China"
      ],
      "name": "Yanyan Wang"
    },
    {
      "affiliations": [
        "Center for Evidence-Based and Translational Medicine, Zhongnan Hospital of Wuhan University, Wuhan, China"
      ],
      "name": "Yinghui Jin"
    },
    {
      "affiliations": [
        "Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Centre, Beijing, China"
      ],
      "name": "Feng Sun"
    },
    {
      "affiliations": [
        "Department of Hypertension and Endocrinology, Daping Hospital, Centre for Hypertension and Metabolic Diseases, Army Medical University of PLA, Chongqing Institute of Hypertension, Chongqing, China"
      ],
      "name": "Zhiming Zhu"
    },
    {
      "affiliations": [
        "Department of Medicine K2, Karolinska Institutet, Stockholm, Sweden"
      ],
      "name": "Lars Rydén"
    },
    {
      "affiliations": [
        "Forschergruppe Diabetes eV at the Helmholtz Centre, Munich-Neuherberg, Germany"
      ],
      "name": "Eberhard Standl"
    },
    {
      "affiliations": [
        "Australian Living Evidence Collaboration (ALEC), Cochrane Australia, School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia"
      ],
      "name": "Tari Turner"
    },
    {
      "affiliations": [
        "MAGIC Evidence Ecosystem Foundation, Oslo, Norway",
        "Department of Medicine, Lovisenberg Diaconal Hospital, Oslo, Norway",
        "co-senior authors of this study"
      ],
      "name": "Per Olav Vandvik"
    },
    {
      "affiliations": [
        "Department of Endocrinology and Metabolism, Laboratory of Diabetes and Metabolism Research, West China Hospital, Sichuan University, Chengdu, 610041, China",
        "MAGIC China Centre, Cochrane China Centre, Chinese Evidence-based Medicine, West China Hospital, Sichuan University, Chengdu, 610041, China",
        "MAGIC Evidence Ecosystem Foundation, Oslo, Norway",
        "co-senior authors of this study"
      ],
      "name": "Sheyu Li"
    }
  ],
  "title": "Medications for adults with type 2 diabetes: a living systematic review and network meta-analysis",
  "uid": "2e0d6f33-4fd9-5bf0-981a-f4206864fa39"
}