Published October 31, 2018
Paresh Dandona, MD, PhD — who led the first pilot studies on how drugs developed for Type 2 diabetes patients might benefit adults with Type 1 diabetes — is launching a major, interventional study with 114 patients in Buffalo and Glasgow, Scotland.
The results of this study could bring these drugs closer to FDA approval for Type 1 diabetes.
Dandona — SUNY Distinguished Professor of medicine and chief of endocrinology, diabetes and metabolism — has been awarded a $1.6 million research grant from JDRF, the leading global organization funding Type 1 diabetes research.
The 52-week study will determine whether patients with Type 1 diabetes benefit when their insulin therapy is supplemented with two drugs designed to treat Type 2 diabetes — semaglutide and dapaglifozin — or with semaglutide alone.
The primary endpoint will be a reduction in patients’ mean baseline hemoglobin A1c (HbA1c) — a measure of sugar in the blood. HbA1c levels for Type 1 diabetics are considered optimal when they are under 7 percent.
Currently, less than 20 percent of patients with Type 1 diabetes have HbA1c of under 7 percent.
Since 2011, Dandona, who is also a physician with UBMD Internal Medicine, and his UB colleagues have been researching new treatments for Type 1 diabetes patients, who, to this day, rely on insulin, either as multiple daily injections or through a continuous subcutaneous infusion. He points out that there have been no other successful therapeutic strategies since insulin was discovered nearly 100 years ago.
“The ongoing challenge is that pronounced swings in blood sugars, from hyperglycemic to hypoglycemic are pretty common, even in Type 1 diabetes patients who have good glycemic control as indicated by HbA1c levels,” Dandona said.
“This has been our motivation — to conduct groundbreaking research that will allow for better blood sugar control by using non-insulin drugs in combination with insulin.”
In 2017, Dandona was the lead author on a study published in Lancet Diabetes Endocrinology that found that approximately 40 percent of the 833 patients with Type 1 diabetes who were taking dapagliflozin reduced their A1c levels by more than 0.5 percent without experiencing severe drops in blood sugar (hypoglycemia).
Dandona explained that any fall in HbA1c of around 0.5 percent is considered significant and can lead to licensing of a drug as an antidiabetic agent.
That 24-week study was the first global multicenter investigation of the drug to test its efficacy and safety in Type 1 diabetes. The double-blind, randomized, three-arm, phase 3 multicenter study was conducted at 143 sites in 17 countries, including the U.S., and it was funded by AstraZeneca and Bristol-Myers Squibb, the companies that partnered to develop dapagliflozin.
In June, Dandona reported at the annual American Diabetes Association meeting that patients taking liraglutide, another drug for Type 2 diabetes, saw 0.57 percent reduction in their hemoglobin A1c, compared to placebo. They needed a significantly lower dose of insulin and had lower systolic blood pressure. Patients also saw a reduction in appetite and caloric intake, and they lost an average of 8 pounds over the duration of the study.
While the researchers will be looking to see positive outcomes when insulin is used in conjunction with either one or both of these drugs, Dandona noted that the triple therapy approach may have an advantage.
“In a small pilot study that we conducted and published in 2016 with triple therapy including insulin, liraglutide and dapagliflozin, the A1c reduction was greater than the sum of actions of liraglutide or dapagliflozin alone when used with insulin,” he said. “Thus, it is possible that semaglutide, which we will be using in this trial, and which is more potent than liraglutide, may synergize the effect of dapagliflozin, leading to even better outcomes.”
He added: “Quite apart from the beneficial effect on HbA1c, which is known to reduce microvascular complications, both semaglutide and dapagliflozin are known to reduce the systolic blood pressure and body weight and to reduce the risk of macrovascular disease and congestive cardiac failure. Thus, the potential benefits of triple therapy in Type 1 diabetes could be multidirectional and immense.”
The mission of JDRF is to accelerate life-changing breakthroughs to cure, prevent and treat Type 1 diabetes and its complications. To accomplish this, JDRF has invested more than $2.2 billion in research funding since its inception.
JDRF collaborates with academic institutions, policymakers and corporate and industry partners to develop and deliver a pipeline of innovative therapies to people living with Type 1 diabetes. Its staff and volunteers throughout the United States and six international affiliates are dedicated to advocacy, community engagement and a vision of a world without Type 1 diabetes.
Dandona’s three-year study will commence in November, supported by John Petrie, MD, PhD, professor of diabetic medicine at the University of Glasgow, as the co-investigator.
UB researchers from the Department of Medicine associated with the study are:
Patients participating in the U.S. will be treated at the Clinical Research Center of the Division of Endocrinology at UB. Patients participating in Scotland will be treated at the University of Glasgow/NHS Greater Glasgow and Clyde Clinical Research Facility in the United Kingdom.