Further support for early combination therapy in type 2 diabetes
medwireNews: Adding the dipeptidyl peptidase (DPP)-4 inhibitor sitagliptin to first-line metformin therapy may delay the need for exogenous insulin among people with type 2 diabetes, researchers report.
These real-world study results are in line with findings from the VERIFY trial, reported previously by medwireNews, which demonstrated durable benefits of early combination therapy with the DPP-4 inhibitor vildagliptin plus metformin.
For the sitagliptin study, Scot Simpson (University of Alberta, Edmonton, Canada) and co-investigators used administrative health databases to compare the need for insulin initiation – as a surrogate for diabetes progression – among 8764 individuals starting treatment with metformin between 2008 and 2015. Of these, 13.2% initiated sitagliptin at the same time as metformin, while 86.8% started sitagliptin at a later date.
“Sitagliptin was chosen because it was the first in class approved for use in Canada and the most commonly dispensed DPP-4 inhibitor in our database,” explain the researchers.
They found that 15.0% of the 1153 people initiating metformin–sitagliptin combination therapy required exogenous insulin use over an average follow-up of 3.9 years, compared with 19.1% of the 7611 patients initiating metformin monotherapy, translating into a significant 24% lower likelihood of insulin requirement among those starting with the combination after adjustment for factors including age, sex, and use of other medications.
Moreover, glycated hemoglobin (HbA1c) levels decreased by a significantly greater degree among individuals starting combination therapy, with average levels of 9.4% at baseline and 7.4% at 1 year, compared with corresponding levels of 8.7% and 7.7% for those initiating metformin alone.
“These two outcomes, a greater reduction in HbA1c and fewer insulin starts in the costart group, are consistent with the hallmarks of successful diabetes therapy, improved glycaemic control and slowed progression of the disease,” write the researchers in Diabetic Medicine.
They caution that their study had a number of limitations, including lack of information on potential confounders such as socioeconomic status and some lifestyle choices, and a “relatively short” duration of follow-up, meaning it was not possible “to assess the risk of clinical outcomes such as microvascular or macrovascular complications or death.”
Nonetheless, the study findings suggest that a delay in adding sitagliptin to metformin therapy “may miss an important window early in the treatment of type 2 diabetes when preservation of β-cell function could be optimized and could thus negate potential long-term benefits,” say Simpson and team.
And they conclude: “Much like early initiation of insulin therapy, costarting sitagliptin with metformin may change the natural history of the disease, which could ultimately lead to fewer medications and a lower risk of complications.”
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