July 19, 2010 — Clinicians do not lack for alternative therapies if patients with type 2 diabetes ask to be switched from rosiglitazone (Avandia, GlaxoSmithKline) to another glucose-lowering medication, according to the American Diabetes Association (ADA) and 2 other expert groups. The drug is again under increased scrutiny over cardiovascular risks.
"I don't think any physician or patient should worry that they don't have a good option if they're uncomfortable with Avandia," Richard Bergenstal, MD, ADA president of medicine and science, told Medscape Medical News.
Dr. Bergenstal, who also is executive director of the International Diabetes Center at Park Nicollet Health Services in St. Louis Park, Minnesota, said published clinical algorithms can guide physicians in selecting the right drug or combination of drugs. Such algorithms, he said, take into account factors such as efficacy, the risk for hypoglycemia, weight gain, and other adverse effects, as well as cost.
"We used to just ask which medication lowers blood sugar the most," he said. "Now it's a little more complicated."
In their joint statement released July 12, the ADA, the Endocrine Society (ES), and the American Association of Clinical Endocrinologists (AACE) urged patients now receiving rosiglitazone to continue taking it unless they receive instructions from their healthcare provider to the contrary.
"Until further clarification is provided by the [US Food and Drug Administration (FDA)], the decision whether or not to use any medication must remain that of the treating provider in direct discussion with the individual patient," the groups said.
The statement came 2 days before an advisory committee to the FDA voted 20–12 with 1 abstention to recommend that the FDA keep rosiglitazone on the market. A majority of members also recommended that the agency add a tougher warning about the risk for heart attacks and other cardiovascular events to the label. This seemingly contradictory conclusion reflects the conflicting drug-safety data that the committee weighed.
Physicians now are waiting to hear from the FDA itself, which has promised to evaluate the advisory committee proceedings and reach a decision as quickly as possible.
Regardless of the FDA's verdict, physicians and patients alike should know that there are multiple classes of drugs, often with more than 1 agent in a class, that can be used to maintain glucose control in patients with type 2 diabetes, according to the statement by the ADA, ES, and AACE:
alpha-glucosidase inhibitors, and
dipeptidyl peptidase-4 inhibitors.
The ADA lists these classes on its Web site.
Rosiglitazone is 1 of 2 FDA-approved medications in the thiazolidinedione class for lowering glucose; the other is pioglitazone (Actos, Takeda Pharmaceuticals). In its deliberations last week, the FDA advisory panel voted 21–4 in affirming that pioglitazone is safer than rosiglitazone.
Consensus Statement Goes Against Rosiglitazone Use
In June, the ADA announced on its Web site that it does not have an official position favoring or recommending against FDA-approved medications to lower glucose. Such positions, however, do appear in a consensus statement of the ADA and the European Association for the Study of Diabetes (EASD) that was published in Diabetes Care in January 2009. The ADA notes that this consensus statement "does not reflect the official position of the ADA but rather the expert opinion of the authors."
For most patients with type 2 diabetes, the consensus statement recommended as a "well-validated core therapy" a combination of lifestyle changes — namely, weight loss and increased physical activity — and metformin (Glucophage; Bristol-Myers Squibb), which belongs to the biguanide class. If this first-tier therapy fails to achieve or maintain glycemic goals, clinicians can prescribe either insulin or a sulfonylurea (except for chlorpropamide or glybenclamide) in addition to metformin.
The consensus group unanimously advised against prescribing rosiglitazone, although it noted that the evidence on the drug's cardiovascular risk is "not conclusive." The group found a second-tier use for its chemical cousin pioglitazone, however: Clinicians may consider it when "hypoglycemia is particularly undesirable (e.g., in patients who have hazardous jobs)," according to the consensus statement.
There is no dearth of algorithms for the role of medications in glycemic control. The AACE and the American College of Endocrinology (ACE) published one last fall that lays out a path from monotherapy to triple therapy. The algorithm prioritizes choices of medication based on "safety, risk of hypoglycemia, efficacy, simplicity, anticipated degree of patient adherence, and the cost of medications." The guidelines from AACE and ACE do not contain a blanket statement against prescribing rosiglitazone.
The International Diabetes Center at Park Nicollet Health Services has developed its own algorithm. Similar to the consensus statement of the ADA and EASD, it recommends pioglitazone, but not rosiglitazone, as part of dual or triple drug therapy when clinicians are targeting insulin resistance.
"Why have a sleepless night about whether you should have prescribed rosiglitazone or not?" said Dr. Bergenstal in explaining the rationale behind the algorithm.
Switching to a New Diabetes Drug Could Pose Greater Risks
The joint statement from the ADA, AACE, and ES informs clinicians and patients that they have alternatives to rosiglitazone but does not advise physicians to automatically switch patients from this drug to something else. That advice echoes that of Daniel Einhorn, MD, the president of the AACE and medical director of the Scripps Whittier Diabetes Institute in La Jolla, California.
If patients tell him that they are worried about continuing with rosiglitazone, Dr. Einhorn said, he will discuss other drug therapies. However, he has not asked patients to stop using rosiglitazone — yet.
"So far, there is no FDA signal to discontinue the drug," he said. "All we can say is that serious safety questions have been raised. If you've done well on Avandia for years, why switch to another drug that may come with more risks for you?"
At the same time, Dr. Einhorn said he is no longer writing new prescriptions for rosiglitazone while the drug is under FDA review, and he doubts that any other physicians are writing them. He acknowledged that the status of the drug is confusing for clinicians, but then, so are the safety data that the FDA advisory committee heard.
"If the data was clear," said Dr. Einhorn, "we wouldn't be having this discussion."
Medscape Medical News © 2010 WebMD, LLC
Send press releases and comments to firstname.lastname@example.org.
Cite this: Patients With Diabetes Have Alternatives to Rosiglitazone, Experts Say - Medscape - Jul 19, 2010.