medwireNews: Use of sodium-glucose cotransporter (SGLT)2 inhibitors rather than sulfonylureas as an addition to metformin therapy may be associated with a reduced mortality risk for people with type 2 diabetes, suggest real-world study findings.
As reported in JAMA Internal Medicine, the researchers identified 128,293 people (average age 64.6 years, 95.2% men) within the Veterans Affairs healthcare system who were taking metformin for type 2 diabetes.
In a linked editorial, Vinay Guduguntla (University of California, San Francisco, USA) and Richard Grant (Kaiser Permanente Northern California, Oakland, USA) note that current guidelines advise use of sulfonylureas as second-line treatment only when cost is an issue.
Yet more than four times more people in this study were given a sulfonylurea (n=104,423) than were given an SGLT2 inhibitor (n=23,870) in addition to metformin.
“Indeed, although use of sulfonylureas is declining, a recent report suggests that they remain the second most prescribed oral agent after metformin,” write the editorialists. “Many patients cannot afford the hundreds of dollars in annual out-of-pocket costs associated with newer oral agents.”
After using propensity scores to balance the baseline characteristics of the two groups, Ziyad Al-Aly (VA St Louis Health Care System, Missouri, USA) and co-researchers found that SGLT2 inhibitor use was associated with a significant mortality risk reduction of 19% compared with sulfonylurea use, equating to 5.15 fewer deaths per 1000 person–years.
They note that they looked at all-cause mortality as an endpoint that “encompasses the breadth of potential SGLT2 inhibitor benefits.”
The survival advantage with SGLT2 inhibitors versus sulfonylureas was consistent across subgroups defined by age, cardiovascular disease, kidney function, BMI, and other variables.
In addition, the combination of an SGLT2 inhibitor and metformin was associated with a significant 30% reduction in mortality risk, or 7.62 fewer deaths per 1000 person–years, compared with use of an SGLT2 inhibitor alone.
Guduguntla and Grant say the study findings suggest that a consequence of the high cost of new medication classes “could be a worsening of health disparities among lower-income patients with diabetes whose choice of agent is driven by short-term affordability.”
They conclude: “While SGLT2 inhibitors have the potential to improve longer-term (and expensive) diabetes-related outcomes, cost barriers mean that many patients (and our health system) cannot afford the apparent mortality benefit associated with SGLT2 inhibitors compared with sulfonylureas.
“High drug pricing must be reined in to reduce current inequities in the treatment of diabetes.”
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JAMA Intern Med 2021; doi:10.1001/jamainternmed.2021.2488