TRENTON, N.J. (AP) -- The maker of the world's best-selling diabetes drug is facing hundreds of lawsuits and likely a big sales drop as suspicion grows that taking the pill for more than a year raises the risk of bladder cancer.In June, Takeda Pharmaceuticals Co. Ltd. halted sales of Actos, its top drug, in Germany and France after pressure from regulators.Since then, both the U.S. Food and Drug Administration and the European Medicines Agency have issued warnings about the cancer risk based on new research, but they have allowed sales to continue. Doctors are being told not to prescribe Actos for people who have or have had bladder cancer.The warning will limit patient choices and could spell the end for a once-promising class of Type 2 diabetes drugs that debuted more than a decade ago amid heavy promotion.The once-a-day pills were appealing. They helped control blood sugar tightly, had few side effects in most patients, boosted the effects of some other diabetes drugs, worked by a new mechanism -- improving the body's sensitivity to insulin -- and even allowed patients to reduce or delay use of injected insulin.Actos, despite links to heart failure risk and other serious side effects, became the No. 1 diabetes pill after Avandia, the only other drug in that class, was found in 2007 to sharply increase risk of heart attacks. Avandia's use was banned in the EU and sharply restricted here. Actos sales jumped from about $2.9 billion in 2006 to more than $4.3 billion last year.Now those billions may well shift to Takeda rivals.In the past week, the first of what lawyers predict will be thousands of lawsuits were filed in courts across the country. They allege Actos triggered bladder cancer, in some cases fatal, in clients who took the pills daily for years.Nancy Rios, 54, is suing Takeda, blaming her recurrent bladder cancer on Actos, which she took for more than a decade. Rios, a hospital secretary, was diagnosed with bladder cancer in 2009. In June, she had her second surgery to remove tumors. Rios, who lives in Reading, Pa., is worried about missing more work and being able to pay her medical bills. Next month, she will learn whether more treatment is needed."I could lose my bladder and possibly need chemo," she said.Her attorney, Paul Pennock of Weitz & Luxenberg, said the firm already represents another 104 clients, has about 120 more expected to pursue lawsuits and is getting 30 to 40 possible new cases a week."When a manufacturer distributes a drug, they owe it to the public to ensure that their product is safe for use and it appears that Takeda Pharmaceuticals failed to fulfill that fundamental duty," Pennock said.Other large law firms are evaluating potential cases by the dozen or more. More than 20 firms, from Florida to Washington state, are advertising for clients on the Internet or in newspapers, a standard practice in personal injury law."We don't think it's a coincidence that we've been contacted by so many people who have been taking Actos and have bladder cancer," said Marc Jay Bern of Napoli Bern Ripka Shkolnik & Associates. "We have more than 100 (cases) that we've confirmed and many more that we're evaluating."Takeda declined to comment on the lawsuits. The company, which is based in Japan, has issued statements that it's committed to keeping Actos available for patients who need it.Spokeswoman Elissa Johnsen noted an April study in the journal Diabetes Care found Actos "use for more than two years was weakly associated with increased risk."However, the FDA analyzed data from the first five years of a 10-year Actos safety study Takeda begun in 2002 and concluded this June that risk of bladder cancer was 40 percent higher for patients taking Actos for at least a year, although still small: an extra 28 cases a year for every 100,000 people taking it.Erik Gordon, an analyst and professor at University of Michigan's Ross School of Business, said Friday that the new safety questions are "a big deal" for Takeda, particularly since the Actos patent expires in August 2012. They mean Actos won't make as much money as expected in the final months, and they dampen prospects for two experimental drugs Takeda was hoping would succeed Actos."One, alogliptin, has been stuck at the FDA over safety concerns, and the other, a combination of alogliptin and Actos, now looks doomed," Gordon said.Alogliptin is an experimental drug in the same class as Merck & Co.'s blockbuster Januvia. Those drugs increase production of insulin, which breaks down sugar in the blood, and reduce glucose production in the liver.Les Funtleyder, an analyst and portfolio manager for the Miller Tabak Health Care Transformation fund, said Januvia is likely to gain sales as patients defect from Actos.He doubts the cost of the bladder cancer litigation will hit the level of Vioxx. That's the painkiller that Merck pulled off the market in 2004 because it doubled risk of heart attacks and strokes -- triggering more than 50,000 lawsuits and, eventually, a $4.85 billion settlement to end most of them.Whatever the outcome of the Actos litigation, diabetes patients and their doctors will be considering their options now.Dr. Harlan Krumholz, a Yale School of Medicine professor who directs its Center for Outcomes Research and Evaluation, said more long-term data on the effects of Actos is needed."It's not clear if this (bladder cancer) risk is real," but Actos and Avandia both are linked to heart risks, weight gain and possibly bone loss and fractures, he said. "The consensus already is that (Actos) should only be considered ... after patients have exhausted all other options."