In a retrospective study that included 209,867 new users of an SGLT2 inhibitor who were matched to 209,867 users of a DPP-4 inhibitor, the SGLT2 users were nearly 25% less likely to experience a major adverse cardiovascular event (MACE), according to the report published in The BMJ.
"These findings confirm that the benefits of these drugs demonstrated in the controlled setting of clinical trials extend to the real-world setting of everyday clinical practice," said lead author Kristian Filion of McGill University and the Lady Davis Institute of the Jewish General Hospital.
But SGLT2 inhibitors may not be for everybody, Filion said in an email.
"While this study confirms the effectiveness of SGLT2 inhibitors for the prevention of cardiovascular events, this drug class has also been associated with some important side effects, such as diabetic ketoacidosis and genital tract infections," Filion cautioned. "While such adverse events are rare and likely outweighed by the cardiovascular and renal benefits of using this drug class, physicians and their patients should consider both the potential benefits and harms when choosing the most appropriate treatment for type 2 diabetes."
To take a closer look at the potential cardiovascular benefits of SGLT2s, Filion and his colleagues turned to the administrative health databases from the Canadian provinces of Alberta, British Columbia, Manitoba, Nova Scotia, Ontario, Quebec and Saskatchewan and the United Kingdom Clinical Practice Research Datalink.
They analyzed data on all adults who received an SGLT2 inhibitor or a DPP-4 inhibitor between January 1, 2006 and June 30, 2018.
Overall, they found, SGLT2 inhibitors were associated with decreased risks of MACE. The incidence rate per 1,000 person years was 11.4 in the SGLT2 group as compared with 16.5 in the DPP-4 group, leading to a hazard ratio of 0.76 overall.
Broken down by the type of MACE, HRs were 0.82 for myocardial infarction, 0.60 for cardiovascular death, and 0.43 for heart failure.
The mechanism for the protective effect of the SGLT2 inhibitors isn't known, although it is unlikely to be due solely to the impact of improved glucose control, Filion said. "Additional effects of SGLT2 inhibitors such as reductions in plasma volume and arterial blood pressure, and changes in arterial stiffness could also play a role," he added.
While there have been clinical trials showing the cardiovascular benefits of SGLT2s, this study offers clinicians a chance to see the impact of these drugs in a real world setting, said Dr. Sandra Sobel, chief of endocrinology at UPMC Mercy, in Pittsburgh.
"As physicians we are tasked with the job of extrapolating the results of studies," Dr. Sobel said. "What is nice about this is it included patients who were not at high risk for cardiovascular disease."
The new study is part of a larger accumulation of studies, said Dr. Jeffrey Mechanick, an endocrinologist and professor of medicine at the Icahn School of Medicine at Mount Sinai and medical director of the Mari-Josee and Henry R. Kravis Center for Cardiovascular Health at Mount Sinai Heart in New York.
One of its strengths is that it compares SGLT2s to another class of diabetes drugs, Dr. Mechanick said. The researchers "took great care to make sure that the individuals in the SGLT2 group were matched with those already being treated with a diabetes medication to see if this class of drug added cardiovascular protection," he said. "And it did."
Dr. Mechanick suspects that newer versions of SGLT2 drugs will have an even bigger impact. "This is only the beginning," he said. "There are a lot more medications coming out in this family and they may have multiple effects, kind of like statins, which help protect the heart in ways beyond reducing lipids."
By Linda Carroll
SOURCE: https://bit.ly/2RXBsJg BMJ, September 23, 2020.
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