Two U.S. senators have asked the inspector general of the Health and Human Services Department to investigate a practice by pharmacy-benefit managers known as spread pricing, as part of a wider inquiry by lawmakers into U.S. drug costs.

Ron Wyden of Oregon, the ranking Democrat on the Senate Finance Committee, said that he and Chairman Chuck Grassley (R-Iowa) have requested the inspector general, which examines the operations of government health programs, to probe the issue. Under spread-pricing arrangements, PBMs charge one amount to health plans for a drug, then reimburse pharmacies a different, often lower amount -- and capture the...