The University of Colorado is part of two large clinical trials now underway that aim to improve care for patients battling type 2 diabetes and those at risk of developing the disease.
The GRADE (Glycemia Reduction Approaches in Diabetes: A Comparative Effectiveness Study) and D2d (Vitamin D and type 2 diabetes) studies are multicenter trials funded by the National Institutes of Health (NIH). They are both well underway, but the university needs to roughly double the number of patients in each to reach its enrollment goals, said Neda Rasouli, MD, an endocrinologist at University of Colorado Hospital (UCH) and director of the CU Diabetes and Endocrinology Trial Program. Rasouli is principal investigator for both studies.
Neda Rasouli, MD (left) and Chantal Underkofler, MS, are leading two NIH-funded studies at CU aimed at decreasing the clinical and economic burden of type 2 diabetes.
Thus far, the trial team has been recruiting patients at UCH identified as candidates from the Epic electronic health record, Rasouli said. They now want to widen the net to bring in UCH and CU employees and people from the community who might qualify.
The GRADE trial, which includes 36 trial sites with a targeted enrollment of 5,000 patients, is studying the effectiveness of frequently prescribed drugs used in combination with the oral medication metformin in controlling blood sugar levels. Patients who have had type 2 diabetes for less than 10 years and have blood sugar that is inadequately controlled with metformin are randomly assigned one of the four drugs. The patients will receive the medications and supplies for free, and an endocrinologist-led research team will follow them through 2019.
Sorting through the meds
Previous studies have pitted one medication against another, but the GRADE trial is taking a much broader perspective, Rasouli noted.
“It is the only study that compares the efficacy of all four treatments together in controlling blood sugar,” she said. That information, together with data on rates of hypoglycemia, incidence of weight gain, occurrence of side effects, and the cost of the medications, promises to help providers make stronger evidence-based treatment decisions, she added.
Today, for example, providers frequently add a second therapy to metformin on the basis of cost, Rasouli said. The disparity is enormous: monthly costs range from roughly $4 to $400. It’s still not clear whether or not a more expensive medication is necessarily the most effective for a given patient.
“We want to personalize the medications we give type 2 diabetes patients, but we do not have enough data on how to choose them,” Rasouli said. “GRADE aims to identify individual patient factors that are associated with response to and failure of medications – with the goal of determining which approaches are likely to work best in which people.”
The D2d study, now underway at 23 sites, is for patients with prediabetes, as measured by levels of blood glucose, HbA1C, and glucose tolerance tests. The goal is to determine what role, if any, vitamin D levels play in insulin secretion or resistance, Rasouli said. Studies have established an association between type 2 diabetes and low levels of vitamin D, but the connection could be the result of poor diet and/or low activity levels, she said. The trial will investigate whether or not there is a causal link.
Patients will be divided into two groups, with one receiving vitamin D and the other a placebo. The national enrollment target is 2,400; the CU team wants to reach 65 patients. Patients in both groups will receive coaching to help them make lifestyle modifications and will be tested regularly for diabetes.
The NIH awarded CU $3.5 million for the GRADE trial and just under $1 million for the D2d study. But the real pay-off lies in identifying new ways to manage a disease that can lead to a variety of life-threatening complications. Finding the most effective medications, ensuring patient compliance with them, and encouraging lifestyle changes could also take a sizable chunk from the economic burden imposed by diabetes: a total of $245 billion in 2012 in direct medical costs and lost productivity, according to the American Diabetes Association. Type 2 diabetes, which affects roughly 90 percent of all patients with the disease – more than 25 million people – is responsible for the bulk of that bill.
“Helping patients get better control over their blood sugar over a long period of time could help to reduce a huge cost burden for the health care system,” said Chantal Underkofler, MS, research manager for the Diabetes and Endocrinology Trial Program.
The GRADE trial could be especially beneficial to patients in that it involves drugs already proven to be effective in controlling blood sugar, as opposed to experimental treatments, Underkofler added.
“Sometimes there is a barrier when patients hear the word ‘research,’” she said. “With this trial, study medications are all FDA-approved. Glycemic control provided by the study is similar to the standards of care patients would receive in clinical practice so that the results are relevant.”
Patients will be closely monitored by physicians and physician assistants, Underkofler added, and will have a direct line to their providers if they have questions or concerns. In addition, if a patient has a poor response to the assigned medication, providers will be able to adjust it.
“The goal is to have the best blood sugar control possible,” she said.
Farther on, the GRADE trial promises to help providers target treatments of type 2 diabetes even more precisely, Rasouli said. For example, additional research could reveal which combinations of medications are best for patients in different ethnic groups or those with comorbidities like heart disease.
“It will take a lot of analysis,” Rasouli said, “but the goal will be to try to find personalized treatments for patients in these groups.”
If you are interested in joining the GRADE or D2d trials, contact Neda Rasouli, MD, at [email protected] check out other clinical trials offered through the CU Diabetes and Endocrinology Trial Program.