Adverse effects with semaglutide: a protocol for a systematic review with meta-analysis and trial sequential analysis

Christina Dam Bjerregaard Sillassen*, Caroline Barkholt Kamp, Johanne Juul Petersen, Pascal Faltermeier, Faiza Siddiqui, Johannes Grand, Helena Dominguez, Anne Frølich, Peter Haulund Gæde, Christian Gluud, Ole Mathiesen, Janus Jakobsen

*Corresponding author for this work

Abstract

INTRODUCTION: Semaglutide is increasingly used for the treatment of type 2 diabetes mellitus, overweight and other conditions. It is well known that semaglutide lowers blood glucose levels and leads to significant weight loss. Still, a systematic review has yet to investigate the adverse effects with semaglutide for all patient groups.

METHODS AND ANALYSIS: We will conduct a systematic review and search major medical databases (Cochrane Central Register of Controlled Trials, Medline, Embase, Latin American and Caribbean Health Sciences Literature, Science Citation Index Expanded, Conference Proceedings Citation Index-Science) and clinical trial registries from their inception and onwards to identify relevant randomised clinical trials. We expect to conduct the literature search in July 2024. Two review authors will independently extract data and perform risk-of-bias assessments. We will include randomised clinical trials comparing oral or subcutaneous semaglutide versus placebo. Primary outcomes will be all-cause mortality and serious adverse events. Secondary outcomes will be myocardial infarction, stroke, all-cause hospitalisation and non-serious adverse events. Data will be synthesised by meta-analyses and trial sequential analysis; risk of bias will be assessed with Cochrane Risk of Bias tool-version 2, an eight-step procedure will be used to assess if the thresholds for statistical and clinical significance are crossed, and the certainty of the evidence will be assessed by Grading of Recommendations, Assessment, Development and Evaluations.

ETHICS AND DISSEMINATION: This protocol does not present any results. Findings of this systematic review will be published in international peer-reviewed scientific journals.

PROSPERO REGISTRATION NUMBER: CRD42024499511.

Original languageEnglish
Article numbere084190
JournalBMJ Open
Volume14
Issue number6
Pages (from-to)e084190
ISSN2044-6055
DOIs
Publication statusPublished - 21 Jun 2024

Keywords

  • Humans
  • Systematic Reviews as Topic
  • Glucagon-Like Peptides/therapeutic use
  • Meta-Analysis as Topic
  • Hypoglycemic Agents/therapeutic use
  • Diabetes Mellitus, Type 2/drug therapy
  • Research Design
  • Randomized Controlled Trials as Topic

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