American Scientist

To the Editors:

Philip A. Rea and Anderson Y. Tien’s article on metformin in the March–April issue is a tour de force that explains the history and utility of this important drug. It was especially significant to my wife (of 65 years), Dr. Barbara Weil, because of the important role she played in the late stage of getting it on the market in the United States. She received a PhD in chemistry from the University of Illinois in 1953. After holding other pharmaceutical-related positions, she was employed beginning around 1980 as Senior Director of Science and Technology at Lipha Pharmaceuticals, Inc., in New York City, an office managed by Dr. Gerard Daniel. Lipha had a French parent company based in Lyon, which had acquired Glucophage from Aron Labs and was marketing it in Europe. Barbara’s job, which took many years, was to get U. S. Food and Drug Administration approval. As your article states, that approval was achieved in 1994. She received the clinical and other data from France and had the task of completing the paperwork for filing with the FDA.

She told me that in an FDA meeting, she had to combat an FDA committee member’s phenformin-related objections by using an organic chemistry argument. Barbara remembers getting a celebratory trip to France, so her major contribution was recognized by Lipha.

Barbara retired some few years later. She is 91 now, and her eyesight is too poor for her to read your fine article, but she is pleased to hear from me that metformin is still important.

Edward Weil
Polytechnic Institute of New York University (Emeritus)
New York, NY

Dr. Rea responds:

What made Dr. Edward Weil’s letter especially intriguing was the role his wife, Dr. Barbara Weil, played in winning FDA approval of metformin. This accomplishment was far from trivial, because many U.S. physicians feared a drug related to metformin’s immediate forerunner, phenformin—a fear borne of their bitter experience as their patients treated with it developed severe lactic acidosis, sometimes with dire consequences. How inspiring to learn that Dr. Barbara Weil was the one who through her powers of persuasion as a card-carrying organic chemist—as someone who knew the fundamentals of carbon chemistry—succeeded in explaining to the FDA committee why they were misled in thinking that metformin necessarily carried the same risks as its “evil twin,” phenformin.

If not for this, metformin (as “Glucophage”) might not have risen to market dominance in this country when in 1994 Bristol-Myers Squibb (BMS) acquired Lipha’s U.S. Glucophage marketing rights in exchange for granting Lipha the marketing rights in France for Monopril, BMS’s once-a-day blood pressure medication. Little did she (or anyone else at the time) know the colossal benefit her actions would have for Americans with type-2 diabetes, who currently number approximately 30 million.

That Dr. Barbara Weil served as Senior Director of Science and Technology for Lipha Pharmaceuticals, Inc., in New York City (which is now owned by Merck KGAA) is also significant. Lipha acquired Aron Laboratories, the French company affiliated with Dr. Jean Sterne, whose brainchild it was to use metformin as a drug for the treatment of type-2 diabetes, way back in the 1950s. There is a direct line of connection between Dr. Barbara Weil and the beginnings of the use of metformin as an oral diabetes medicine. Her legacy is to be celebrated!