Two classes of glucose-lowering medications, sodium-glucose cotransporter-2 (SGLT2) inhibitors and glucagon-like peptide-1 receptor agonists (GLP-1RA), improve cardiovascular outcomes of patients with type 2 diabetes with established cardiovascular disease. But their use in clinical practice remains relatively low, with a preference for sulfonylureas and dipeptidyl peptidase-4 (DPP-4) inhibitors, researchers note in the Journal of the American Heart Association, online July 16.
Dr. Gian Paolo Fadini of the University of Padova, Italy, and colleagues at 12 outpatient clinics in Italy investigated whether the occurrence of a cardiovascular event in patients with type 2 diabetes primed changes in the prescription patterns by diabetes specialists.
Among 563 patients with a cardiovascular event, including 497 matched with controls not having a cardiovascular event, the most common glucose-lowering medications at baseline were metformin, sulfonylureas, DPP-4 inhibitors and insulin.
During 9.5 months of follow-up, the only significant difference in glucose-lowering medication prescribing between the matched groups was a decline in metformin prescribing among cases with cardiovascular events.
Among patients who were withdrawn from metformin after a cardiovascular event, insulin prescribing increased from 41.2% to 66.7%, compared with only a slight increase (from 48.3% to 49.5%) among patients without a cardiovascular event.
In contrast, there were significant increases in the prescription of cardiovascular medications (statins, angiotensin-converting enzyme inhibitors, diuretics, and antiplatelet agents) during follow-up in both groups.
Patients with cardiovascular events experienced significant improvements in diastolic blood pressure, total and LDL cholesterol, and triglycerides, as well as declines in estimated glomerular filtration rate and no significant change in hemoglobin A1c.
“This study highlights that occurrence of a cardiovascular event in type 2 diabetes patients did not prime the prescription of glucose-lowering medications provided with cardiovascular protective effects, even though glucose control remained poor,” the researchers conclude. “These data emphasize the need to optimize the therapeutic regimen of type 2 diabetes patients with established cardiovascular disease, according to updated guidelines.”
Dr. Jacob A. Udell of Women’s College Hospital, in Toronto, Canada, who contributed to the Canadian clinical practice guidelines on cardiovascular protection in people with diabetes, told Reuters Health by email, “We need more collective experience reporting on this phenomenon, discussing with front-line physicians and academic leaders why there continues to be hesitancy, primarily I’m told because of the rare but life-threatening potential risk of complications when patients fall ill (e.g., diabetic ketoacidosis, renal injury), and discuss how to mitigate these concerns, as we have established for a multitude of other (now considered) ‘traditional’ cardioprotective medications.”
“We also need the pharmaceutical industry to invest in more studies of these agents in more representative patients being seen in everyday practice, either as an education and implementation initiative or as part of a ‘pragmatic’ randomized trial performed within clinical registries or in regions throughout North America where we can track outcomes using health insurance claims data and get real-time (anonymized and privacy-protected) information of the benefit and side effect risk seen in the ‘real world,’ where proven drugs are being deployed by front-line physicians,” he said.
“Translation of new discoveries with proven benefit to the bedside continues to take a very long time, likely from multifactorial barriers, including drug approval by health regulatory bodies, drug cost coverage by public or private insurance, prescribing inertia or hesitancy for fear of affordability, understanding, side effects, or need for oversight/education that takes too long, and patient’s may not wish to try something new or understand the responsibility that comes with medicines that need to be held during sick days,” said Dr. Udell, who was not involved in the new work.
“It’s a good start to see a study like this, and more research like this is needed to better understand the barrier and enablers to new medications being used in routine practice,” he added.
The study did not have commercial funding, but several authors report ties to manufacturers of antidiabetics.
Dr. Fadini did not respond to a request for comments.
J Am Heart Assoc 2019.