GLP-1 and Pioglitazone Work Together to Lower Glucose
Issue 219 Item 3

Treatment with GLP-1 alone or with pioglitazone was linked to decreased appetite. In patients with type 2 diabetes, combination therapy with glucagon-like peptide (GLP)-1 and pioglitazone lowers blood glucose levels to a greater extent than either agent alone.

Although GLP-1 and pioglitazone both reduce blood glucose levels, the mechanisms that each employs are different, which may explain the apparent synergistic effect when used in combination, according to the investigators. GLP-1 works by stimulating insulin secretion and inhibiting glucagon secretion, whereas pioglitazone works by sensitizing muscle and fat cells to insulin.

Dr. Mette Zander, from Hvidovre Hospital and colleagues conducted a crossover study in which eight patients with type 2 diabetes were treated with GLP-1, pioglitazone, both agents, or saline and observed for 48 hours.

The average fasting plasma glucose level fell from 13.5 mmol/L with saline to about 11.6 mmol/L when GLP-1 or pioglitazone was given. However, the lowest level –9.9 mmol/L–was seen when these agents were used together (p < 0.001). Similar findings were seen with 8-hour mean plasma glucose levels.

Compared with saline, combination therapy was associated with a reduction in free fatty acids during breakfast (p = 0.03). Treatment with GLP-1 alone or with pioglitazone was linked to decreased appetite, a finding that has been observed in several previous studies.

Based on these results, the team concludes, that combination therapy with GLP-1 and pioglitazone could be a "valuable therapeutic approach" for type 2 diabetes. Diabetes Care 2004;27:1910-1914.
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