The GLP-1 analog, liraglutide, previously approved for the treatment of type 2 diabetes mellitus (T2DM), is also approved as a weight loss agent at a dose of 3 mg daily. In the SCALE diabetes trial, there was an average of about 4% placebo-subtracted weight loss and HbA1c reduction of 1% more than placebo and statistically better in both regards than the 1.8-mg dosing. Liraglutide at all doses consistently improves cardiometabolic risk factors including lipids and blood pressure with slightly increased heart rate. A pooled post hoc analysis of the phase 3 trials involving liraglutide 3 mg suggested possible cardiovascular benefit but with small numbers of events and wide confidence intervals. Further reassurance of cardiovascular safety, and perhaps benefit, could be drawn from the benefits shown in the LEADER trial of 1.8-mg liraglutide in patients with T2DM and high-risk (and high prevalence of established) CVD.
The other medications are not preferred for reducing CV risk in this patient with established ascvd and CKD3b though could be considered. Orlistat reduces cardiovascular risk factors and has no cardiovascular safety concerns but has not shown cardiovascular event reduction and is not as beneficial for this patients glycemic control and renal benefits. Sympathomimetics, like phentermine in the combination of phentermine/topiramate ER, are to be used in caution for patients at increased cardiovascular risk. While the cardiovascular safety of phentermine/topiramate ER is not established, data from the phase 3 trials are reassuring thus far. Weight loss with naltrexone/bupropion ER is accompanied by improvements of several cardiometabolic parameters, though blood pressure generally remained higher than placebo in trials. A cardiovascular outcome trial was initiated for naltrexone/bupropion ER with reassuring early data, though with high discontinuation rate, but the trial had to be terminated due to public compromise of that data; thus, the cardiovascular safety has not been determined.
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