TY - JOUR
T1 - Adverse effects with tirzepatide
T2 - a protocol for a systematic review with meta-analysis and Trial Sequential Analysis
AU - Sillassen, Christina Dam Bjerregaard
AU - Petersen, Johanne Juul
AU - Kamp, Caroline Barkholt
AU - Grand, Johannes
AU - Dominguez, Helena
AU - Frølich, Anne
AU - Gæde, Peter Haulund
AU - Gluud, Christian
AU - Mathiesen, Ole
AU - Jakobsen, Janus C
N1 - © Author(s) (or their employer(s)) 2025. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ Group.
PY - 2025/4/15
Y1 - 2025/4/15
N2 - INTRODUCTION: Cardiovascular diseases remain the leading cause of mortality worldwide. Tirzepatide is approved for the treatment of type 2 diabetes mellitus and overweight and is increasingly used. The adverse effects with tirzepatide may not be disease-specific and have not been assessed previously.METHODS AND ANALYSIS: We will conduct a systematic review and search major medical databases (Cochrane Central Register of Controlled Trials, Medical Literature Analysis and Retrieval System Online (MEDLINE), Excerpta Medica database (EMBASE), Latin American and Caribbean Health Sciences Literature (LILACS), Science Citation Index Expanded (SCI-EXPANDED), Conference Proceedings Citation Index-Science (CPCI-S)) and clinical trial registries from their inception and onwards to identify relevant randomised clinical trials. We expect to conduct the literature search in January 2025. Two review authors will independently extract data and perform risk of bias assessments. We will include randomised clinical trials comparing tirzepatide versus placebo or no intervention in all patient groups with an increased risk of cardiovascular events. 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 the Cochrane Risk of Bias tool-version 2. We will systematically 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: CRD42024599035.
AB - INTRODUCTION: Cardiovascular diseases remain the leading cause of mortality worldwide. Tirzepatide is approved for the treatment of type 2 diabetes mellitus and overweight and is increasingly used. The adverse effects with tirzepatide may not be disease-specific and have not been assessed previously.METHODS AND ANALYSIS: We will conduct a systematic review and search major medical databases (Cochrane Central Register of Controlled Trials, Medical Literature Analysis and Retrieval System Online (MEDLINE), Excerpta Medica database (EMBASE), Latin American and Caribbean Health Sciences Literature (LILACS), Science Citation Index Expanded (SCI-EXPANDED), Conference Proceedings Citation Index-Science (CPCI-S)) and clinical trial registries from their inception and onwards to identify relevant randomised clinical trials. We expect to conduct the literature search in January 2025. Two review authors will independently extract data and perform risk of bias assessments. We will include randomised clinical trials comparing tirzepatide versus placebo or no intervention in all patient groups with an increased risk of cardiovascular events. 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 the Cochrane Risk of Bias tool-version 2. We will systematically 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: CRD42024599035.
KW - Humans
KW - Systematic Reviews as Topic
KW - Meta-Analysis as Topic
KW - Research Design
KW - Diabetes Mellitus, Type 2/drug therapy
KW - Cardiovascular Diseases
KW - Hypoglycemic Agents/adverse effects
KW - Randomized Controlled Trials as Topic
KW - Tirzepatide
KW - PUBLIC HEALTH
KW - Meta-Analysis
KW - Systematic Review
KW - Safety
UR - http://www.scopus.com/inward/record.url?scp=105003391851&partnerID=8YFLogxK
U2 - 10.1136/bmjopen-2024-094947
DO - 10.1136/bmjopen-2024-094947
M3 - Review
C2 - 40233950
SN - 2044-6055
VL - 15
JO - BMJ Open
JF - BMJ Open
IS - 4
M1 - e094947
ER -