Administration of the oral antidiabetic drug (OAD) repaglinide along with rosiglitazone, a differently acting OAD, improves glycaemic control better than therapy with either agent alone, according to a study published in the current issue of Diabetic Medicine.

The study is the first full report of a clinical trial evaluating this combination OAD regimen. Another recent study demonstrated similar findings with a similar OAD, pioglitazone.

“When type 2 diabetes progresses – as it usually does – maintaining adequate control of blood glucose often requires escalating from the usual, initial OAD monotherapy to combination OAD therapy,” said lead investigator Philip Raskin, MD, professor of medicine at the University of Texas Southwestern Medical Center in Dallas, Texas.

He added, “Based on their different and complementary actions, a regimen combining repaglinide with rosiglitazone is a logical approach when OAD monotherapy does not adequately maintain glycemic control.” He explained that repaglinide, which stimulates insulin secretion for a short period of time, is taken with meals to control the surge in blood glucose following food consumption (postprandial hyperglycemia); rosiglitazone acts differently, increasing the body’s sensitivity to insulin.

The 24-week, open-label, randomized, multicentre trial enrolled 252 adult participants with type 2 diabetes who had inadequate glycaemic control, as determined by A1C levels (>7 per cent, the upper end of the desired level, and < 12 per cent). A1C is the per cent haemoglobin with glucose attached, and is an indicator of long-term glycaemic control. The participants had been treated for at least three months before entering the study with either a sulfonylurea, which stimulates insulin production, or metformin, which increases the body’s responsiveness to insulin.

Upon entering the study, the participants’ prior therapy was withdrawn for two weeks, and they were randomly assigned to either repaglinide + rosiglitazone combination therapy, or repaglinide or rosiglitazone monotherapy in a 2:1:1 ratio. In the first 12 weeks of therapy, repaglinide and rosiglitazone doses were optimized for each participant, followed by 12 weeks of maintenance therapy.

Baseline A1C values were similar for the combination, repaglinide-only and rosiglitazone-only groups (9.1 per cent, 9.3 per cent and 9.0 per cent, respectively). By the end of the study, average A1C values decreased much more compared to baseline in the combination group compared to the repaglinide or rosiglitazone monotherapy groups: – 1.43 per cent vs. –0.17 per cent and – 0.56 per cent, respectively (p < 0.001).

The reduction in A1C values for the combination group was significantly greater than the reduction in the two monotherapy groups combined (p < 0.01). In the combination group, 39 per cent of participants had final A1C levels at or below 7 per cent, compared to only 5 per cent in the repaglinide-only group and 16 percent in the rosiglitazone-only group.

Average values of fasting plasma glucose also decreased compared to baseline much more in the combination group compared to repaglinide and rosiglitazone monotherapy groups: - 94 mg/dl, -54 and -67 mg/dl, respectively (p < 0.001). Changes in blood lipid levels were generally similar in all three groups.

The rate of discontinuation, largely because of lack of efficacy, was lowest for the combination group compared to the repaglinide and rosiglitazone groups: 16.5 per cent, 39.7 per cent and 40.3 per cent, respectively. Among all participants, one in the combination therapy group experienced a major episode of hypoglycemia (requiring assistance).

Minor episodes of hypoglycaemia were experienced by 9 per cent, 6 per cent and 2 per cent of participants in the combination, repaglinide-only and rosiglitazone-only groups, respectively. Mean changes in weight from baseline were +4.4 kg, +1.6 kg, and +2.3 kg, respectively.

“Overall, these findings show that the combination of repaglinide and rosiglitazone is safe, well-tolerated and effective in improving glycaemic control of patients with type 2 diabetes, and should be considered a promising treatment option in appropriate patients,” said Dr Raskin.