Troglitazone can reduce insulin for type II diabetics
Troglitazone can reduce insulin for type II diabetics
Drug expected to be approved by FDA soon
A new oral diabetes agent expected to reach the U.S. market soon will radically change the way type II diabetes is treated. The drug, troglitazone (Rezulin), is expected to reduce or eliminate the need for insulin, says Steve Mock, spokesman for Warner-Lambert in Morris Plains, NJ, makers of the drug.
An advisory panel to the U.S. Food and Drug Administration (FDA) in Rockville, MD, recently recommended approval of troglitazone, but the FDA is still reviewing data on the drug before giving it final approval.
Troglitazone is the first agent in a new class of oral antidiabetic drugs, the thiazolidinediones. (See related story, p. 33.) It directly reduces insulin resistance, which is the key to the underlying cause of type II diabetes, Mock says. Once it is approved by the FDA, troglitazone will be indicated for type II diabetics who aren’t adequately controlled on insulin. Those are patients who previously failed to achieve adequate control on other oral agents. In patients who require insulin, troglitazone significantly lowers blood glucose levels and can reduce or eliminate the need for injected insulin.
"This drug is an insulin-sensitizing agent," says Edward Horton, MD, vice president of Joslin Diabetes Center and a professor of medicine at Harvard Medical School, both in Boston. Horton was an investigator in clinical pre-marketing trials of the drug. "This is the first class of drugs that has come along that gets at the underlying problem in type II diabetes. The drugs counteract insulin resistance by sensitizing the tissues to insulin action and make the insulin more effective."
Philip Cryer, MD, president of the American Diabetes Association in Alexandria, VA, agrees. "This drug represents a new class of drugs for the treatment of type II diabetes that increases sensitivity to insulin, which makes a given amount of insulin more effective in lowering blood sugar." Cryer is also a professor of medicine at Washington University in St. Louis, MO.
Marjorie Cypress, RN, MS, nurse practitioner and certified diabetes educator at Lovelace Health Systems in Albuquerque, NM, says the drug will probably be used most often in conjunction with other oral antidiabetic medications there.
"There are a lot of people with type II diabetes where the major defect is insulin resistance," she notes. "For these people, this drug will be very good. We’ll have to see what our patients’ response is to [troglitazone], but we’re hoping to use it in patients who are on very high doses of insulin who we know have insulin resistance. Adding in this drug may lower their insulin requirements."
Troglitazone doesn’t totally replace insulin in most patients, however. In pre-marketing studies of the drugs, 51% to 70% of patients were able to reduce their insulin doses by more than 50%, but only 7% to 15% were able to completely eliminate insulin injections from their treatment regimens. In addition, Cryer says troglitazone isn’t typically used as first-line therapy. The other oral antidiabetic agents such as metformin or miglitol are tried first, and when patients fail on them and require insulin, then troglitazone should be used, either alone or in combination with other oral agents. (See "New Drug Update" column on miglitol, p. 35.)
However, Horton says he believes that soon after troglitazone is approved for insulin-dependent type II diabetics, the drug will be approved for all type II diabetics as possible first-line therapy. But the real benefit appears to be for insulin-dependent patients.
"This is very good news, because there is a lot of concern about insulin resistance as an underlying factor in the development of some of the long-term complications of diabetes, particularly heart disease," he adds. "So we think that getting people onto lower doses of insulin is going to be really beneficial. There’s no data to prove that, but we know that better glucose control has a major impact to reduce the long-term complications of diabetes. This drug will help achieve better blood glucose control. In that sense, it will reduce the risk for long-term complications. Whether it has additional effects by combating the insulin resistance still has to be tested."
Troglitazone is not appropriate for type I diabetics, Horton says. "This drug doesn’t replace insulin, it just makes the [existing] insulin more effective, he says. "A type I diabetic who has no insulin in [his or her] own body will still have to take insulin injections."
Although actual product insert labeling is not available for the drug until it is approved, Horton says pre-marketing trials did indicate that troglitazone affected blood cholesterol levels. "The LDL [low-density lipoprotein] level went up a little bit in the pilot trial, but the HDL (high-density lipoprotein] went up even more," he notes. "So the actual ratio of LDL to HDL cholesterol was better. We think that’s a good effect — not a bad effect."
In addition, some patients experienced lowered hemoglobin and hematocrit counts while on the drug, Horton notes. "But [those counts] were still within normal range, so it’s not clinically significant," he says. "The overall side-effect profile [indicates] it’s a very well-tolerated drug. There wasn’t any increase in the usual types of side effects we see with medications such as gastrointestinal upsets or skin rashes compared to [patients] on placebos."
What about weight gain?
An advantage of troglitazone is that there is no weight gain associated with it such as with other oral antidiabetic agents. But the drug isn’t a substitute for "proper diet and exercise," Horton adds. "That’s really fundamental to all treatment of diabetes," he says.
"As someone who has taken care of people with diabetes for over 30 years, [I can say] we’ve needed new drugs desperately," Horton says. "Now, with this drug, this gives us more mileage. This is a tremendous addition to our armamentarium of medications we can use in people with type II diabetes."
Cryer agrees. "It’s something else that can be added to a treatment program," he says.
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