BACKGROUND: Randomized, controlled trials (RCTs) comparing the effectiveness of metabolic bariatric surgery (MBS) in addition to one or more treatment interventions for obesity (i.e., lifestyle structured interventions-LSI, medical therapy-MT, obesity management medication-OMM or endobariatric procedures-EP) are lacking. This study aims to assess the effectiveness of multiple simultaneous (before or immediately after MBS) interventions for treating obesity. METHODS: We performed a meta-analysis including all RCTs enrolling patients undergoing different MBS procedures add-on to other anti-obesity strategies (LSI, MT, OMM or ES) versus MBS alone, with a duration of at least 6 months. The primary outcome was BMI at the end-point; secondary end-points included percentage total and excess weight loss (%TWL%, and EBWL%), total weight loss (TWL), fasting plasma glucose (FPG), HbA1c, surgical and non-surgical severe adverse events (SAE), mortality, remission of type 2 diabetes, hypertension, dyslipidemia and health-related quality of life (HR-QoL). RESULTS: A total of 25 RCTs were retrieved. The addition of either OMM (i.e., liraglutide) or EP (i.e., intragastric balloon-IB, endosleeve-ES) to MBS was associated with a significantly lower BMI at the end-point (p = 0.040). The addition of liraglutide only to MBS was associated with a greater %EWL%, but not %TWL and TBWL (p = 0.008). Three trials evaluated end-point HbA1c, showing a significant reduction in favour of liraglutide as an add-on therapy to MBS (p = 0.007). There was no mortality. CONCLUSIONS: MBS combined with non-surgical approaches appears more effective than MBS alone in reducing BMI. Further RCTs on combined therapies to MBS for severe obesity are needed to enhance the tailoring of treatment for severe obesity.

Bariatric and Metabolic Surgery Unit Department of General and Laparoscopic Surgery Ospedale Evangelico Betania Naples Italy

Centro Multidisciplinar Do Tratamento da Obesidade Hospital Lusíadas Amadora e Lisboa Amadora Portugal

Delta CHIREC Hospital Brussels Belgium

Department of Bariatric and Metabolic Surgery Medical Center Center for Obesity Northern Netherlands Leeuwarden The Netherlands

Department of General Emergency and Metabolic Surgery Rovigo Hospital Rovigo Italy

Department of General Surgery Holy Family Hospital Nazareth Israel

Department of Medical Surgical Sciences and Translational Medicine Sant'Andrea Hospital Sapienza University Rome Italy

Department of Molecular and Clinical Medicine Institute of Medicine Göteborg Sweden

Department of Surgery and Transplantation University Hospital Zurich University of Zurich Zurich Switzerland

Department of Surgery Bariatric Endoscopy Medical Faculty Mannheim Heidelberg University Heidelberg Germany

Department of Surgery Catharina Hospital Eindhoven The Netherlands

Department of Surgery Cerrahpasa Medical Faculty Istanbul University Istanbul Turkey

Department of Surgery Faculty of Medicine and Health Örebro University Örebro Sweden

Department of Surgery Ponderas Academic Hospital Bucharest Romania

Department of Surgery University of Turku Turku Finland

Department of Surgery Whittington Hospital University College London UK

Department of Surgical Sciences University of Tor Vergata Rome Italy

Diabetic Foot Unit University of Florence and AOU Careggi Florence Italy

Digestive Surgery and Liver Transplantation Unit Université Côte d'Azur Nice France

Division of Visceral Surgery Department of General Surgery Medical University of Vienna Vienna Austria

Endocrine Metabolic and Bariatric Surgery Unit Vall Hebron Barcelona Hospital Campus Universitat Autònoma de Barcelona Barcelona Spain

General and Digestive Surgery Department Fuenlabrada University Hospital Rey Juan Carlos University Madrid Spain

HM Delfos Barcelona Spain

OB Klinika Center for Treatment of Obesity and Metabolic Disorders Prague Czech Republic

Public Health Department School of Medicine University Federico 2 of Naples Naples Italy

San Marco Hospital GSD Zingonia Italy

The Azrieli Faculty of Medicine Bar Ilan University Ramat Gan Israel

The Center for Obesity and Diabetes Hospital Alemao Oswaldo Cruz Sao Paulo Brazil

University of Messina Messina Italy

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