Highlights From the Latest in Diabetes Research

In the U.S., national data indicate that 71 million adults aged 20 years—33.5% of this age-group—have elevated LDL cholesterol. Of these, only 34 million are being treated and 23 million (about 33% of all patients) had their LDL cholesterol at targets defi ned by the National Cholesterol Education Program/ Adult Treatment Panel III (NCEP/ATP III). These data indicate that there is considerable room for improvement in initiating or identifying an effective treatment among people with elevated LDL cholesterol and that treatment goals are not where they should be among individuals who are being actively treated. The obesity epidemic and the aging of the populations in many developing countries may conspire to increase the prevalence of elevated LDL cholesterol in the future, a trend that will require added attention to initiating effective treatment in affected individuals. Given the high prevalence of elevated LDL cholesterol, it is of some concern that 10–20% of patients are unable to tolerate statins, which are currently the most effi cacious therapy for reducing LDL cholesterol. The primary reason for statin intolerance in these patients is their impact on muscle pain and weakness. As a result, statins are not an attractive treatment option for a large proportion of the affected patient population, a problem that may increase in tandem with increases in the prevalence of elevated LDL in the population as a whole. The GAUSS trial addressed the need for effective therapies among individuals for whom statins are not a viable option. The trial focused on AMG145, a monoclonal antibody to PCSK9, which is involved in LDL receptor function. The phase 2 study randomized 160 statin-intolerant patients aged 18–75 years at 33 sites. Patients were allocated to one of three AMG145 doses (280 mg, 350 mg, or 420 mg), AMG145 420 mg + 10 mg ezetimibe, or 10 mg ezetimibe + placebo. The primary end point was percent change in LDL cholesterol between baseline and week 12. A number of secondary and exploratory end points were also examined, including absolute change in LDL cholesterol, percent change in HDL cholesterol, and adjudicated clinical cardiovascular events and mortality. The results were striking: LDL cholesterol was reduced 41, 43, and 51% in the AMG145 280 mg, 350 mg, and 420 mg groups, respectively, and 61% among participants who received AMG145 420 mg + 10 mg ezetimibe. In contrast, LDL cholesterol was reduced by only 15% in the 10 mg ezetimibe + placebo group. AMG145 also resulted in modest increases in HDL cholesterol. Sixty and fi ftynine percent of patients receiving AMG145 and 10 mg ezetimibe + placebo reported adverse events. Of the four serious adverse events, all were in the AMG145 group and none were determined to be associated with treatment. Given that the magnitude of AMG145’s impact on LDL cholesterol reduction was similar to that commonly observed with statins, the results of the GAUSS trial may offer promise for millions of patients who do not currently have access to a treatment option that permits them to achieve NCEP goals. — Helaine E. Resnick, PhD, MPH