Intensifying Therapy, Adding Sitagliptin Better for Achieving Glycemic Targets

Results from a study involving adding sitagliptin and increasing doses of metformin for patients who cannot attain glycemic control show that as glycated hemoglobin increases, it becomes harder to reach targets.

When patients with type 2 diabetes (T2D) don’t achieve their glycemic targets, waiting to boost doses of metformin or add another therapy, such as sitagliptin (Januvia), can hurt their chances of achieving glycemic control, according to an abstract presented Sunday at the 79th Scientific Sessions of the American Diabetes Association (ADA) in San Francisco, California.

The study,1 funded by Merck, compared patients with T2D who had not met glycated hemoglobin (A1C) targets after taking 1000 mg a day of metformin. Patients were given either sitagliptin or placebo while their metformin dose increased to 2000 mg/day. The participants had a baseline A1C of ≥7.5%, with a mean A1C of 8.6%. Targets were 6.5% to 8.0%, depending on baseline and other factors.

Those taking sitagliptin achieved better glycemic control and were more likely to reach their A1C goal, with similar safety and tolerability to placebo.

While patients in the study had a range of A1C targets, the researchers noted that the farther patients were from their goal when their medication was intensified, the less likely they were to achieve it. “These results suggest that the distance to A1C goal should be considered throughout the process of metformin uptitration to inform antihyperglycemic agent intensification strategy, including the potential benefit of early sitagliptin initiation,” the authors wrote.

Clinical inertia. The results highlight the challenge of clinical inertia, which refers generally to the failure to intensify a patient’s treatment even when evidence-based goals are not being met. A separate study presented Sunday, from Merck’s Center for Observational and Real-World Evidence, found that sociodemographic factors, such as race and age, may be associated with the failure to add or intensify therapy.2

Swapnil Rajpathak, MBBS, DrPH, executive director for the cardiometabolic section of the center, told The American Journal of Managed Care® that until recently, most of the research into disparities in diabetes has involved disease burden. Merck’s center has spent several years gathering evidence about disparities in disease management, such as the study on clinical inertia being presented at ADA.

“We know there is disparity in the levels of control. We are hypothesizing that clinical inertia may contribute to that disparity,” said Rajpathak, who was the senior author on the study.

Using 2015 data from the GE Centricity Electronic Medical Record Data Base, researchers identified T2D patients taking metformin and at least 1 other antihyperglycemic agent, had at least 12 months of enrollment prior to starting dual therapy and had their therapy intensified at some point after that.

Results suggest that older patients were less likely to have their therapy intensified at higher A1C levels than younger patients. Compared with whites, black patients were more likely to be intensified at higher A1C levels. There was no apparent pattern of intensification by geographic region.

Does this mean physicians are waiting until black patients have higher A1C levels to give them an additional drug for T2D? Rajpathak said that can’t be inferred from the data.

“Clinical inertia doesn’t always equal physician inertia,” he said. “That’s a common misconception.” Lack of treatment intensification can be related to patient factors—if a physician knows that the patient isn’t taking the prescribed medication, he may try to get the patient to stick with a dosing schedule first, instead of adding a prescription the patient may not take.

Rajpathak said factors such as a physician’s lack of time can also contribute to the problem. The Merck group now wants to test different solutions to overcoming clinical inertia, such as prompts from an electronic health record.

The Merck group’s work on disparities suggests that besides racial and age differences, insurance status can also affect whether clinical inertia occurs. The task now is to test targeted solutions. “Clinical inertia awareness is important—not just in the United States—it’s a global issue,” he said.


  1. Crutchlow M, Lin J, Lam RL. A1C goal attainment after metformin (MET) uptitration with and without Sitagliptin (SITA): impact of baseline and target A1C. Presented at: American Diabetes Association 79th Scientific Sessions, San Francisco, CA; June 7-11, 2019. Abstract number 1149-P. doi: 10.2337/db19-1149-P.
  2. Fernandes G, Sawhney B, Hannachi H, et al. Clinical inertia in relation to sociodemographic factors among patients with type 2 diabetes (T2D) in the United States. Presented at: American Diabetes Association 79th Scientific Sessions, San Francisco, CA; June 7-11, 2019. Abstract number 1496-P. doi: 10.2337/db19-1496-P.
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