Long-term treatment with orlistat (120 mg, 3 times a day [TID]) is associated with improvements in cardiovascular risk factors such as total and LDL cholesterol, fasting glucose, and systolic and diastolic blood pressure.35,36Orlistat may also help prevent progression to type 2 diabetes in adults with obesity.37

In clinical studies, lorcaserin was associated with improvements in blood pressure, total cholesterol, LDL cholesterol, and triglycerides.19,21,22In patients with type 2 diabetes, lorcaserin produced a larger reduction in fasting plasma glucose and HbA1Cthan did placebo.19,34

Because phentermine is a sympathomimetic drug, phentermine monotherapy may increase pulse or blood pressure despite weight loss, or counteract the beneficial effects of weight loss on these measures. Therefore, according to the prescribing information, phentermine is contraindicated in patients with a history of cardiovascular disease.15

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However, phentermine/topiramate produces weight loss and is associated with significant improvements in blood pressure, glycemic measures, high-density lipoprotein (HDL) cholesterol, and triglycerides.20,23,24,38In patients with a higher incidence of cardiovascular and metabolic risk factors, treatment with phentermine/topiramate for 2 years has been associated with a reduction in the number of antihypertensive and lipid-lowering medications used.18,24

In persons without type 2 diabetes, treatment with phentermine/topiramate reduced mean fasting glucose and insulin concentrations, indicating improved insulin sensitivity, and slowed the progression to diabetes. In patients with type 2 diabetes, treatment with phentermine/topiramate was associated with reduced HbA1Cand with little or no change in the number of diabetes medications used.24

Naltrexone/bupropion is associated with improvements in triglycerides, HDL cholesterol, LDL cholesterol, and insulin sensitivity.26-28In patients with type 2 diabetes, treatment with naltrexone/bupropion also improved HbA1C.25The beneficial effect of weight loss on blood pressure is attenuated with naltrexone/bupropion (likely due to the sympathomimetic effects of bupropion). The long-term cardiovascular safety of naltrexone/bupropion is currently under investigation.15

Because liraglutide is a GLP-1 receptor agonist, it has benefits in addition to weight loss. Liraglutide is currently approved for the treatment of type 2 diabetes. It may improve HbA1C, β-cell function, and systolic blood pressure39while also reducing body fat.29In obese individuals without diabetes, liraglutide is associated with improvements in blood pressure and lipids as well as reductions in the development of metabolic syndrome, prediabetes, and diabetes.29,30