Can SGLT2 Inhibitors Protect Our SLE Patients?

Plenary Session 2 Highlights Sodium-Glucose Co-Transporter-2 Inhibitors at ACR Convergence 2023

Dr. April Jorge

SAN DIEGO—The ACR Convergence Plenary Sessions highlight selected abstracts of interest to the general ACR audience. In the second plenary session this year, April M. Jorge, MD, assistant professor of medicine, Harvard Medical School and director of the lupus program, Massachusetts General Hospital, Boston, shared fascinating results on the potential cardio- and renal-protective benefits of sodium-glucose co-transporter-2 inhibitors (SGLT2i) in patients with systemic lupus erythematosus (SLE) and lupus nephritis.¹

Background

Dr. Jorge commenced her talk with some sobering facts. “Despite recent improvements in SLE treatment, patients with SLE and [lupus nephritis] have an increased risk of cardiovascular (CV) events and kidney failure,” Dr. Jorge said. “In fact, the CV risk is more than double that of the general population. Up to 50% of patients with SLE will develop [lupus nephritis], and 10–30% of these patients will progress to end-stage renal disease (ESRD). There is a major unmet need to improve these outcomes.”

Sodium-glucose co-transporter-2 inhibitors are a class of oral hypoglycemic agents that have been found to reduce the progression of chronic kidney disease and prevent major adverse cardiovascular events (MACE), independent of glycemic control. There are multiple proposed mechanisms of action for these benefits, including anti-inflammatory effects.² The trouble is that patients with SLE have been excluded from trials that demonstrated these benefits—until now.

Objective & Study Design

Jorge et al. sought to determine the impact of SGLT2i vs. a comparator oral hypoglycemic agent (dipeptidyl peptidase 4 inhibitors [DPP4i]) on kidney and CV outcomes in patients with SLE and lupus nephritis. They used a target trial emulation framework. ³

The target trial emulation framework is essentially a hypothetical randomized controlled trial (RCT) using real-world observational data. Dr. Jorge explained, “With this framework, it’s important to state all the key protocol components and specify how you will emulate each using your observational data.”

Randomization of treatment assignment was emulated with propensity score overlap weighting such that baseline patient characteristics were balanced between groups.

The researchers used observational data from a multi-center electronic health records database that included patient information from 46 healthcare organizations across the U.S. Given the use of oral hypoglycemics, these were patients with SLE, as well as a subgroup with lupus nephritis, who also had type 2 diabetes (DM2) and were initiated on any of the FDA-approved SGLT2i (e.g., canagliflozin) and DPP4i (e.g., sitagliptin) in the U.S. Patients with ESRD were excluded.