DOI: 10.1111/dom.71511 ISSN: 1462-8902
Association Between Weight Loss on Incretin‐Based Therapy and Cardiovascular Outcomes and Mortality: A Systematic Review and Meta‐Regression
Marko Skelin, Bruna Perkov‐Stipičin, Vlatka Bračić, Zvonimir Marko Škugor, Ivan Krečak ABSTRACT
Aims
The primary aim was to evaluate, using aggregate‐data meta‐regression, whether body weight loss induced by incretin mimetic therapy is associated with reductions in three‐point major adverse cardiovascular events (
3P
‐
MACE
), individual cardiovascular outcomes and mortality. A secondary aim was to estimate the overall cardiovascular effects of incretin mimetics compared with placebo.
Methods
A systematic review of placebo‐controlled randomized trials was conducted using
MEDLINE
,
EMBASE
,
CENTRAL
and ClinicalTrials.gov. Eligible trials reported cardiovascular hazard ratios (
HRs
) and weight changes. The primary analysis was an aggregate‐data meta‐regression, with the prespecified moderator defined as the placebo‐adjusted percentage weight difference at the latest reported follow‐up time point. Standard meta‐analysis was performed to estimate overall treatment effects.
Results
Sixteen randomized trials including 97 199 participants with and without diabetes were analysed. Meta‐regression showed no statistically significant association between greater body weight loss and treatment
HRs
for
3P
‐
MACE
, cardiovascular or all‐cause mortality, myocardial infarction, stroke and hospitalization for heart failure (
HHF
). These findings do not establish an individual‐level or causal relationship. Meta‐analysis showed significant reductions in
3P
‐
MACE
(15%), cardiovascular mortality (13%), all‐cause mortality (12%), myocardial infarction (14%), stroke (13%) and
HHF
(10%).
Conclusion
Greater trial‐level placebo‐adjusted body weight loss was not significantly associated with lower treatment
HRs
for the cardiovascular and mortality outcomes examined, including
3P
‐
MACE
and
HHF
. These findings do not exclude an individual‐level contribution of weight loss to cardiovascular benefit or establish causality. Individual‐participant‐level analyses are needed to clarify the relationship between weight loss and cardiovascular outcomes.