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NEW YORK (Reuters Health) – When metformin fails to sufficiently lower blood glucose levels, it’s better to add a sodium-glucose cotransporter 2 (SGLT2) inhibitor rather than a sulfonylurea, according to a comparative effectiveness analysis.

Sulfonylureas are the most commonly prescribed second-line diabetes medications, yet how they compare to SGLT2 inhibitors is unclear.

To investigate, Dr. Yan Xie of the VA St Louis Health Care System and colleagues compared the use of SGLT2 inhibitors versus sulfonylureas in more than 128,000 veterans receiving metformin for type-2 diabetes; 23,870 added a SGLT2 inhibitor and 104, ativan 1 mg q8h 423 added a sulfonylurea as a second medication.

Over an average of about two years, adding a SGLT2 inhibitor was associated with a reduced risk of dying from any cause compared to adding a sulfonylurea, regardless of age, cardiovascular disease, or estimated glomerular filtration rate (hazard ratio, 0.81; 95% confidence interval, 0.75 to 0.87).

In addition, continued use of an SGLT2 inhibitor was associated with a reduced risk of death compared with continued use of a sulfonylurea (HR, 0.66; 95% CI, 0.60 to 0.74) and continued use of a SGLT2 inhibitor with metformin was associated with a reduced risk of death compared with a SGLT2 inhibitor alone (HR, 0.70; 95% CI, 0.50 to 0.97).

“The results provide data from a real-world setting that might help guide the choice of anti-hyperglycemic therapy,” Dr. Xie and colleagues write in JAMA Internal Medicine.

The authors of an Editor’s Note say these findings “reinforce” current American Diabetes Association (ADA) guidelines, which advise metformin as initial therapy followed by a dipeptidyl peptidase-4 inhibitor, glucagon-like peptide-1 receptor agonist, thiazolidinedione, or SGLT2 inhibitor class medicine when hemoglobin A1c remains elevated.

Sulfonylureas are recommended as second-line agents only if cost is a major barrier, write Dr. Vinay Guduguntla, editorial fellow with JAMA Internal Medicine, and Dr. Richard Grant, associate editor of the journal.

The current study, they say, makes it clear that the cost of newer agents, such as SGLT2 inhibitors, “remains a major barrier,” as most patients were prescribed sulfonylureas as their second agent.

“Many patients cannot afford the hundreds of dollars in annual out-of-pocket costs associated with newer oral agents,” they point out, and this analysis suggests that a consequence of this cost barrier could be a “worsening of health disparities among lower-income patients with diabetes whose choice of agent is driven by short-term affordability.”

“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,” Dr. Gudunguntla and Dr. Grant conclude.

SOURCE: and JAMA Internal Medicine, online June 28, 2021.

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