Sitagliptin, pioglitazone combination of lasting benefit to drug naïve patients
MedWire News: Starting patients with Type 2 diabetes on a combination of sitagliptin and pioglitazone provides a substantial and lasting reduction in glycated hemoglobin (HbA1c) over 54 weeks of treatment, show study findings.
The combination regimen reduced HbA1c levels significantly further than did pioglitazone monotherapy in previously untreated patients, write Helmut Steinberg (Merck Research Laboratories, Rahway, New Jersey, USA) in Diabetes, Obesity and Metabolism.
The findings come from a 30-week extension of a 24-week randomized, double-blind trial in which 446 diabetes patients with an HbA1c of 8.0 to 12.0% were randomized to either a combination of sitagliptin (100 mg/day) and pioglitazone (30 mg/day) or pioglitazone (30 mg/day) alone.
Of the original participants, 317 entered the extension study. They remained on the treatment they were originally allocated to, but in both groups the dose of pioglitazone was increased from 30 to 45 mg per day after week 24.
At 54 weeks, the team assessed the patients' mean changes from baseline in HbA1c, fasting plasma glucose (FPG), and lipid profile and compared the safety and tolerability of the two regimens.
The researchers report that the mean reductions in HbA1c and FPG were significantly greater with the combination treatment than with pioglitazone monotherapy, at 2.4% versus 1.9% and 61.3 mg/dL versus 52.8 mg/dL, respectively.
However, they note that HbA1c and FPG levels showed no further reductions from baseline between week 24 and week 54 with either treatment.
The combination of sitagliptin and pioglitazone resulted in a higher proportion of patients achieving an HbA1c of less than 7.0% than pioglitazone alone did, at 60.9% versus 35.6%, giving a between-group difference of 25.3%, similar to the 28.9% difference at week 24.
The authors say that if these findings are reproduced in other clinical studies, it would contribute to a rationale for initiating combination therapy at lower doses of pioglitazone rather than uptitrating pioglitazone monotherapy to the maximally allowed dose, and to consider initial combination therapy for patients with higher baseline HbA1c levels.
The researchers also report that both treatment groups had similar reductions from baseline in triglyceride levels and similar increases in high-density lipoprotein cholesterol at week 54, while neither group had a significant change in low-density lipoprotein cholesterol.
In addition, the incidence of adverse and hypoglycemic events did not differ significantly between the groups during the study.
"The observed greater long-term efficacy of initial combination therapy with sitagliptin and pioglitazone, without a significant increase in adverse effects compared with pioglitazone monotherapy, provides support for consideration of using this combination therapy in appropriate patients with moderately or greatly elevated HbA1c at initiation of therapy," concludes the team.
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By Sally Robertson