Older, cheaper oral drugs for treating type 2 diabetes have a similar safety and efficacy profile to newer products, according to the latest research.
The study, conducted by researchers from The John Hopkins Evidence-based Practice Center, and published in the Annals of Internal Medicine, analysed data from 216 clinical trials and cohort studies and two systematic reviews of diabetes research involving the newer oral drugs thiazolidinediones, alpha-glucosidase inhibitors, and meglitinides, and the older agents, metformin and second-generation sulfonylureas.
They found that metformin was similar to, or better than, other currently available oral agents. Second-generation sulfonylureas also fared well against other agents, apart from the increased risk of hypoglycemia. Compared with newer drugs, metformin and second-generation sulfonylureas were found to have the additional advantages of lower cost, longer use in practice and intensive scrutiny in long-term trials with clinically relevant endpoints.
By contrast, researchers found that thiazolidinediones - including GlaxoSmithKline's Avandia (rosiglitazone) - pose a lower risk of hypoglycemia and a “slight” beneficial effect on HDL cholesterol level, but showed no advantage in lowering glucose, and were associated with adverse effects on LDL cholesterol levels, body weight, and risk of congestive heart failure.
“Compared with newer, more expensive agents, older agents have similar or superior effects on glycemic control and other cardiovascular risk factors,” researchers noted, adding that “overall metformin seemed to have the best profile of benefit to risk”.
They did remark, however, that there were no comparative studies showing definitive evidence on how these drug classes improved mortality, concluding that long-term comparative studies on major clinical endpoints, such as myocardial infarction, chronic kidney disease and cardiovascular mortality, are needed, especially in the light of recent controversy regarding Avandia.
Misleading conclusions, says GSK
A spokesperson for GlaxoSmithKline dismissed the findings and suggested they were not in the best interest of patients. In a statement to PharmaTimes World News, the company wrote: ‘The exclusion of data from the ADOPT study, the only long-term study directly comparing a thiazolidinedione (Avandia) with metformin and a sulfonylurea (glyburide) generates misleading conclusions about the glycemic benefits of Avandia. ADOPT demonstrated that Avandia was superior to metformin and sulfonylurea regarding long-term control of blood sugar over five years, which is a key goal in managing diabetes to avoid complications of the disease.’ GSK also said the review excludes interim data from RECORD, the company’s long-term clinical outcomes study which shows no significant difference between the Avandia and control groups in the key outcomes of hospitalisation or death due to cardiovascular events. ‘This type of analysis… serves only to add to the concern and fear that patients on Avandia are experiencing,’ it added.
About seven million people worldwide have taken Avandia and around 1 million US residents are thought to be currently using the drug. However, Avandia has been under a heavy cloud since May when top US cardiologist Dr Steven Nissen published a meta analysis of 42 previous trials that showed the drug increased the risk of heart attack by 43%. The number of prescriptions for Avandia fell dramatically after the study was published, although GSK contends that other studies found no increased risk of heart problems.
Letter campaign to lawyers
The company is taking aggressive measures to defend Avandia, its second-best-selling drug after the asthma treatment Advair, and has initiated a letter campaign to lawyers who have been running television ads targeting Avandia users, objecting to statements by the lawyers that the drug has been linked to heart attacks and death. “Lawyers have a right to advertise, but they have to play by the rules just like we do,” said Chris Viehbacher, President of GlaxoSmithKline in the US.
In the meantime, the US Food and Drug Administration has issued waivers for conflicts of interest to six members of the advisory committee that will review Avandia.