Source: DGNews  |  Posted 8 years ago

By Jill Stein

PARIS, FRANCE -- September 4, 2003 -- The addition of rosiglitazone (Avandia) or glibenclamide to metformin in type 2 diabetic patients previously on other metformin combinations results in similar significant fasting plasma glucose decreases.

However, only metformin plus rosiglitazone therapy is associated with an improvement in insulin sensitivity, according to a study reported here on August 29th at the 18th International Diabetes Federation (IDF) Congress.

Dr. Alex Cobitz, with GlaxoSmithKline, King of Prussia, Pennsylvania, presented the results of a 24-week, double-blind comparative study. Patients were randomized to the insulin sensitizer rosiglitazone plus metformin or the sulfonylurea glibenclamide plus metformin. The 141 type 2 diabetics enrolled in the study were previously on other metformin combination therapies.

"The U.K. Prospective Diabetes Study has documented a progressive loss of glucose control on monotherapy within 3 years after a diagnosis of type 2 diabetes," Dr. Cobitz pointed out. "Subsequently, combination therapy using two agents with complementary modes of action is frequently used to maximize therapeutic effect and decrease side effects."

Increasingly, guidelines are being established that call for aggressive management of glycemia in type 2 diabetics to reduce long-term complications, he continued. However, despite the benefits associated with tighter glycemic control, intensive intervention with combination therapy may often be limited by the potential risk of developing hypoglycemia.

Rosiglitazone and metformin lower plasma glucose concentrations by different mechanisms of action. Dr. Cobitz and colleagues theorized that, when used in combination, these two agents might offer a therapeutic advantage. They measured insulin sensitivity by the homeostasis model assessment (HOMA) technique.

Results of their study showed that the addition of rosiglitazone to metformin resulted in a median increase of 9.4% in measures of insulin sensitivity while glibenclamide plus metformin resulted in a median decline of 0.1%.

While similar control of fasting plasma glucose was achieved with both regimens, episodes of hypoglycemia were approximately 4.5 times more common in the glibenclamide group than the rosiglitazone group (13.3% versus 2.9%).

Gastrointestinal adverse events were more common in the glibenclamide group compared with the rosiglitazone group (25.3% versus 14.3%).

"The results of the study document the benefits of combining two anti-diabetic drugs with complementary mechanisms of action," commented study co-author Dr. Mark Strachan, Western General Hospital, Edinburgh, United Kingdom. "Treatment with rosiglitazone plus metformin decreased blood glucose levels in patients previously on metformin and significantly reduced insulin resistance, a core defect of type 2 diabetes. Treatment with rosiglitazone plus metformin also offered advantages over a sulfonylurea-metformin combination regimen since it was associated with a lower risk of hypoglycemia."

The study was sponsored by GlaxoSmithKline, King of Prussia, Pennsylvania.

[Study title: Benefits beyond glycaemia of adding rosiglitazone rather than glibenclamide to metformin monotherapy in Type 2 diabetes mellitus. Abstract 835]