medwireNews: Patients with type 2 diabetes who are uptitrating to a maximum metformin dose benefit from improved glycemic control when they simultaneously initiate sitagliptin, randomized trial findings suggest.
Michael Crutchlow (Merck & Co., Inc., Upper Gwynedd, Pennsylvania, USA) and colleagues say that the typical stepped-care approach to type 2 diabetes treatment intensification “can substantially delay HbA1c [glycated hemoglobin] goal attainment in patients who ultimately require two or more [anti-hyperglycemic agents] for optimal glycemic control.”
They believe that their data show that “early initiation of sitagliptin may be a safe and effective treatment-intensification strategy” for patients who do not reach their HbA1c goal on a sub-maximal dose of metformin.
“Therefore, early initiation of sitagliptin may effectively address clinical inertia and speed HbA1c goal attainment for many patients who are unlikely to achieve target glycemic control through metformin dose up-titration alone,” the authors write in Diabetes, Obesity and Metabolism.
The phase III CompoSIT-M study included 458 participants, with a mean type 2 diabetes duration of 6.3 years, who had a HbA1c level between 7.5% and 11.0% (mean 8.7%) while using metformin 1000 mg/day.
Among the 229 patients randomly assigned to undergo metformin dose escalation to 2000 mg/day with simultaneous initiation of sitagliptin 100 mg/day, the least squares mean fall in HbA1c from baseline to 20 weeks was 1.10%.
This was significantly greater than the fall of 0.69% observed among the 229 patients who received placebo alongside metformin uptitration.
The researchers note that although a fall of 0.69% would be considered clinically meaningful, the proportion of patients who reached the HbA1c target of below 7.0% was poor in the placebo group overall, at 16.6%, and even worse among those with a baseline HbA1c of at least 8.5%, at 5.7%.
The corresponding proportions achieving HbA1c target were significantly higher in the sitagliptin group, at 28.8% and 15.6%.
The study also showed that patients who received sitagliptin had a significantly greater least squares mean decrease in fasting plasma glucose from baseline to 20 weeks compared with those who received placebo, at 1.6 versus 0.9 mmol/L, from baseline levels of 10.1 and 10.2 mmol/L, respectively.
Crutchlow and co-authors note that there were no significant differences between the sitagliptin and placebo groups in the adverse event rates overall (44.1 vs 45.9%) or in the proportion who experienced at least one documented hypoglycemic episode (2.6 vs 0.9%). There were no serious drug-related adverse events and no cases of severe hypoglycemia in either group.
The researchers conclude that their findings “are consistent with the extensive body of data demonstrating that sitagliptin effectively and safely improves glycemic control when used in combination with metformin.”
By Laura Cowen
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