A 46-year-old man comes to the office to follow up mixed hyperlipidemia. His lipid levels have progressively worsened over the last 10 years associated with gradual weight gain. In the last 6 months, the patient has attempted to modify his diet and exercise regimen, but his lipid levels have not improved. Past medical history is unremarkable, and he currently takes no medications. The patient does not use tobacco, alcohol, or illicit drugs. Blood pressure is 130/86 mm Hg, pulse is 76/min, and BMI is 28 kg/m². Cardiovascular examination is normal. Which of the following drugs, when used as monotherapy, would be most likely to increase triglyceride levels in this patient?

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11ec160b_3bb6_0b16_9249_05360aaa0776_MD0001_00 Bile acid-binding resins (eg, cholestyramine, colestipol, colesevelam) work by binding bile acids in the gastrointestinal tract, inhibiting enterohepatic circulation. This leads to diversion of hepatic cholesterol to synthesis of new bile acids, increased uptake of LDL cholesterol from the circulation, and reduced blood LDL levels. The main side effects of bile acid-binding resins are gastrointestinal upset and impaired absorption of nutrients and drugs. In addition, bile acid-binding resins increase hepatic production of triglycerides and increase the release of triglyceride-heavy VLDL particles into the circulation, leading to hypertriglyceridemia. (Choice A) Statins cause modest reductions in triglyceride levels by decreasing synthesis and increasing clearance of VLDL particles. (Choice C) Ezetimibe selectively inhibits the intestinal absorption of cholesterol and lowers LDL levels. Ezetimibe does not affect triglyceride absorption but may lower blood triglyceride levels slightly. (Choice D) Fibrates (eg, gemfibrozil, fenofibrate) inhibit hepatic production of triglycerides and are first-line treatments for hypertriglyceridemia. (Choice E) Niacin reduces blood triglyceride levels, raises HDL levels, and decreases VLDL conversion to LDL, thereby decreasing LDL concentrations as well. Educational objective: Bile acid-binding resins inhibit the enterohepatic circulation of bile acids. This leads to diversion of hepatic cholesterol to synthesis of new bile acids, increased uptake of cholesterol from the circulation, and reduced blood LDL levels. However, bile acid-binding resins increase hepatic production of triglycerides and can cause hypertriglyceridemia.

A 46-Year-Old Man Comes to the Office to Follow Up