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A second factor is metabolic adaptation
OyelereSFAjayiOHAyoadeTESantana PereiraGBDayo OwoyemiBCIlesanmiAOet al
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42) In SUSTAIN-6, patients treated with semaglutide had a lower risk of developing or worsening nephropathy, but a higher risk of complications from diabetic retinopathy than those receiving placebo ( In subsequent studies: PIONEER-6 and ELIXA the primary endpoints (death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke, hospitalization for unstable angina) were not met in the GLP-1 RAs group, but a significant decrease in glycated hemoglobin was observed
In that work, TMAO accelerated atherosclerosis in mice, and in human subjects undergoing cardiac evaluation, plasma carnitine predicted cardiovascular risk but notably only among those with concurrently high TMAO levels
