How to prioritize CV risk reduction in type 2 diabetes
(1st of two parts)
In the opinion of a doctor, the paradigm of treating patients with type 2 diabetes should shift from a narrow focus on hemoglobin A control to a broader strategy of reducing cardiovascular risk.
“We already know that the No. 1 killer of patients with diabetes is cardiovascular disease, and we already know that lowering HbA1c as a general strategy does not substantially lower the risk of most important CVD events.”
“So, if the goal of treatment is simply to have HbA1c look better in the medical record, then the current approach makes a lot of sense. “But if your goal of treatment is to prevent death and disability in patients with type 2 diabetes, it does not make such sense. You’re pretending that lowering A1c with one drug class is exactly the same as doing it with another drug class, and we already know that’s not the case.”
Physicians know that some medications lower the risk of cardiovascular events including cardiovascular death substantially, and other drugs don’t. “The bottom line is that we are not talking about ignoring HbA1c but it’s how you get there that’s important, how you do it and in whom.”
He pointed to a meta-analysis of four large diabetes trials involving 27,049 participants and 2,370 major vascular events. It found that the general strategy of targeting more-intensive glucose lowering modestly reduced nonfatal myocardial infarction and increased major hypoglycemia over 4.4 years in people with type 2 diabetes – yet there was no difference in the effect of intensive glucose control on cardiovascular death or hospitalization for heart failure.
“Some point to the benefit of glucose control on the risk of nonfatal myocardial infarction, but that’s a modest benefit. “It’s observed beyond the randomization phase of clinical trials and takes many years to see it. It’s a large, very long-term investment for a modest reduction in MI risk, with no benefit in death or heart failure. So, when you test intensive glucose control as a general strategy, it has not been successful in reducing cardiovascular complication of type 2 diabetes.”
However, there is now evidence that specific classes of medications, such as sodium-glucose co-transporter-2 (SGLT20) inhibitors and glucagonlike peptide-1 (GLP-1) receptor agonists, initially developed for glucose lowering in type 2 diabetes, can significantly reduce cardiovascular risk within a relatively short time frame.
In EMPA-REG (Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients), the first trial to demonstrate such benefits, all patients had established CVD, compared with 67% of patients in CANVAS (Canagliflozin Cardiovascular Assessment Study).
A second randomized, controlled trial program to report cardiovascular outcomes with SGLT2 inhibitors. In the meantime, about 15%-20% of patients in real-world clinical practice have established CVD.
This led associates to launch CVD-REAL (Comparative Effectiveness of Cardiovascular Outcomes In New Users of SGLT2 Inhibitors), a real-world comparative effectiveness study that evaluated hospitalization for heart failure and total mortality among new users of SGLT2 inhibitors, compared with other glucose-lowering drugs.
In all, 154,528 patients in six countries were initiated on an SGLT2 inhibitor, and 154,528 were initiated on other glucose-lowering drugs. The greatest exposure time was observed from canagliflozin (53%) followed by dapagliflozin (42%) and empagliflozin (5%). (To be continued)