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Prolonged HbA1c reduction with pioglitazone

Tristan Manalac
08 Feb 2018

Even after discontinuation, pioglitazone (PIO) results in a relatively prolonged reduction in blood glucose levels in Japanese patients with early type 2 diabetes, a recent study has shown.

“[T]he pharmacological intervention with [PIO] for 18 months provide[d] a relatively longer remission of hyperglycaemia after interruption of the medication in type 2 diabetic patients with early stage of disease,” said researchers.

“In our knowledge, the [present] study is the first trial to elucidate whether the temporary intensive treatment with oral antidiabetic medication could modify the natural history of diabetes and/or achieve remission in patients with type 2 diabetes,” they added.

Researchers randomized 278 type 2 diabetes patients (disease duration <5 years) to receive either lifestyle modification (LFS; n=84), PIO (n=101) or sulfonylurea (SU; n=93). During the on-treatment phase 1 of the study, SU was the most potent in reducing HbA1c levels, while LFS failed to produce substantial changes over time. [J Diabetes Investig 2018;doi:10.1111/jdi.12813]

When the two medications were compared at phase 2, after treatment discontinuation, PIO appeared superior to SU. A higher proportion of patients reached HbA1c 7.4 percent in the SU group (14.3 vs 22.2 percent) and the duration of keeping HbA1c <7.4 percent was significantly longer in the PIO group (271.1 vs 133.6 days; p<0.03).

In terms of atherogenic markers, only PIO led to significantly increased serum adiponectin levels and decreased high-sensitivity C-reactive protein (hs-CRP) and homeostasis model assessment of insulin resistance (HOMA-IR) scores. By the end of the study, adiponectin and proinsulin levels were statistically comparable among all three groups.

“In patients who dropped out due to HbA1c elevation … average days to maintain the HbA1c level <7.4 percent was much longer in PIO group compared with SU group,” said researchers.

“[T]he proportion of patients who could keep their HbA1c <6.2 percent throughout phase 2 was numerically highest in PIO group, and average days kept HbA1c <6.2 percent in patients whose HbA1c reached 6.2 percent in phase 2 were also the longest in PIO group,” they added, suggesting that PIO had better sustainability for glycaemic control.

For the first 18 months of treatment, oral antidiabetic drugs were more effective than LFS in lowering HbA1c levels, with mean durations of 530.5 and 545.6 days of HbA1c <7.9 percent in the PIO and SU groups, respectively, compared with 527.6 days in the LFS group. Attrition due to HbA1C >7.9 percent was also significantly higher in the LFS group.

In phase 2, LFS appeared more effective than both antidiabetics in keeping the HbA1c levels <7.4 percent. Attrition due to elevation of HbA1c above the cut-off gradually increased with the discontinuation of the drugs.

The average duration of HbA1c <7.4 percent was higher in the LFS group (547.5 days) than both the PIO (508.1 days) and SU (445.5 days) groups.

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