Recent clinical trials studying the safety and efficacy of sodium-glucose co-transporter-2 (SGLT2) inhibitors and glucagon-like peptide-1 (GLP-1) receptor agonists in patients with diabetes have created opportunities for collaboration with cardiologists and nephrologists.
A joint American Diabetes Association/American College of Cardiologist (ACC) mini-symposium on Friday addressed some of lessons learned from these studies in regard to cardiovascular and renal disease, and also provided a look at the future of collaborative research efforts.
Jean-François Yale, MD, FRCPC, Professor of Medicine at McGill University in Montreal, Canada, reviewed some of the controversies born from the studies. Dr. Yale said data indicates the use of SGLT2 inhibitors and GLP-1 agonists should not be conditional on background metformin or baseline A1C.
“Metformin remains very cheap to give and safe, with no weight gain or hypoglycemia,” he said.
Dr. Yale said evidence is lacking about the effects of SGLT2 inhibitors and GLP-1 agonists in patients with lower or no cardiovascular risk. And while the evidence of cardio-renal benefits is even less, he said the treatments offer the advantage of weight loss, no hypoglycemia, and greater potency, although at a higher cost.
“In extending them to those with chronic kidney disease, I think we must use SGLT inhibitors in people with estimated glomerular filtration rate (eGFR) between 30 and 60. That’s the population that will benefit the most,” Dr. Yale said. “Under 30, GLP-1 agonists keep their benefits, and we need more data with SGLT inhibitors in that range because maybe they work even though the eGFR is very low.”
Dr. Yale also highlighted ways to reduce costs associated with the therapies, including ordering the larger dosage pill of SGLT2 inhibitors and then cutting the pills in half, or taking advantage of the price structure of semaglutide pens.
Sandeep Das, MD, MPH, Associate Professor of Internal Medicine in the Cardiology Division at the University of Texas Southwestern Medical Center, discussed how data from a variety of recent trials offered opportunities for synergy in the care of patients with diabetes.
“My take-home as a cardiologist looking at the data, I would say certainly for canagliflozin and empagliflozin, a 15 percent reduction in major adverse cardiac events (MACE), a 30 percent reduction in heart failure hospitalization, and a 35 percent reduction in kidney disease composites—this is how I see their potential advantage in my patient population,” Dr. Das said.
Darren K. McGuire, MD, MHSc, Distinguished Teaching Professor and the Dallas Heart Ball Chair for Research on Heart Disease in Women at the University of Texas Southwestern Medical Center, concluded the session with a rapid-fire look at 13 clinical trials either ongoing or currently recruiting participants that are studying the use of SGLT2 inhibitors and GLP-1 agonists in patients with and without diabetes for additional applications.
“We have an abundance of data, but we’ve also taken a lot of lessons from the data that have accumulated to design the next phase of trials,” said Dr. McGuire, adding that upcoming trials will add 85,000 patients to the data pool with results coming in the next one to seven years. The ongoing and future trials he reviewed fall under three umbrellas: MACE outcomes trials, heart failure trials, and chronic kidney disease.
“It’s been an exciting 10 years since the regulatory guidance has changed. We’re really encouraged that the FDA has been very flexible and entertaining of the additional outcomes instead of the pre-specified and prescribed three-point MACE outcome,” he said.