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Meta-analyses in diabetic populations have found a correlation between reductions in HbA1c and GLP-1RA-mediated MACE risk reduction.[37, 38] The SELECT trial, which enrolled patients without diabetes but with pre-existing cardiovascular disease (CVD) and a BMI 27, found a significant reduction in MACE among those treated with semaglutide, leading to FDA approval for MACE reduction in individuals with established CVD.[18, 39] A meta-analysis incorporating SELECT and other CVOTs concluded that GLP-1RAs provide a significant MACE reduction in individuals without diabetes, though the reduction in individuals with diabetes is more pronounced.[12] These findings of benefit in populations without diabetes suggest that while the antihyperglycemic effects of GLP-1RAs likely contribute to MACE reduction, other mechanisms, such as systolic blood pressure reduction, likely also play a role.[40] Over time, clinical trials on GLP-1RA MACE reduction have shifted from a focus on secondary prevention, with over 80% of participants in earlier trials such as LEADER and SUSTAIN 6 having a history of established cardiovascular disease, to an emphasis on primary prevention in high risk participants, with less than a third of participants in REWIND having a history of established cardiovascular disease.[8, 10, 11, 41] While semaglutide is currently only FDA-approved for secondary prevention of cardiovascular disease, a meta-analysis of GLP-1RA outcome trials found no significant difference in cardiovascular event relative risk reduction between use for primary versus secondary prevention

The people who run into real trouble are the ones who take it two or three days early, effectively creating a five-day or four-day cycle instead of seven

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As noted, endogenous GLP-1 has a very short half-life of 12 min because it is rapidly degraded by the enzyme DPP-4, which results in low systemic levels

It should also recognize that obesity is a chronic medical condition, not a short-term character flaw

Even if it seems like a good idea that should work, if the evidence isnt there, then such a treatment should only proceed in a setting that can generate the essential evidence. Jeff Levin-Scherz, M.D., the population health leader for health and benefits in North America at Willis Towers Watson, noted that GLP-1 drugs have been in use since 2005