In patients with type 2 diabetes and CVD, empagliflozin reduced incident or worsening nephropathy at 3.1 y

A subanalysis of a trial of empagliflozin for patients with cardiovascular disease (CVD) found lower rates of nephropathy in those randomized to empagliflozin rather than placebo. Of 4,124 patients assigned to the empagliflozin group and 2,061 assigned to the placebo group, 12.7% and 18.8%, respectively, developed incident or worsening nephropathy. Serum creatinine level doubled in 1.5% of the empagliflozin group and 2.6% of the placebo group, while renal replacement therapy was started in 0.3% versus 0.6% in each group, respectively.

The study was published in the July 28 New England Journal of Medicine and summarized in the July ACP Diabetes Monthly. The following commentary by Tejas Patel, MD, MPH, MBA, FACP, was published in the ACP Journal Club section of the Oct. 18 Annals of Internal Medicine.

The prespecified secondary analysis of the EMPA-REG OUTCOME trial reports interesting findings about empagliflozin. This is in a new class of antidiabetes drugs that inhibit sodium–glucose co-transporter 2 (SGLT2), which is responsible for glucose reabsorption in proximal renal tubules. It is important to consider several points before changing our practice. First, no dose–response relation was found: 10 mg and 25 mg of empagliflozin did not differ for clinical outcomes. Second, the US Food and Drug Administration issued a warning about potential SGLT2 inhibitor–associated ketoacidosis. However, the trial reported no significant treatment difference for these events, probably due to low power. Third, the cost of the drug may be prohibitive. Finally, the highly selective patient cohort in the EMPA-REG OUTCOME trial limits external validity.

Given these limitations, what should be the next steps? Comparative effectiveness analysis of various treatment strategies may help shed light on risks and benefits. In addition, longer, larger trials and patient-level meta-analysis would give a better idea about the population that may benefit from this class of drug. Cost-effectiveness analyses are also needed to assess the benefit–cost ratio of the drug, especially for entities that approve drugs for reimbursement in their patient populations. Until then, we should continue to pursue multifactorial interventions to reduce complications. Given the growing burden of type 2 diabetes, cost-effective interventions are urgently needed to avoid end-stage renal disease, which is equivalent to death in most developing countries.