Study Estimates Lifetime Benefit of SGLT2, GLP-1 RA, Nonsteroidal MRA Use in Type 2 Diabetes

In the last 10 years, cardiovascular and renal risk management among patients with type 2 diabetes has been revolutionized as the result of advances in pharmacological therapy.

Driven by GLP-1 receptor agonists, SGLT2 inhibitors, and, most recently, nonsteroidal mineralocorticoid receptor agonists, many have hypothesized about the magnitude of benefit combination therapy might offer. Now, a new study is providing clinicians with insight into the estimated lifetime cardiovascular, kidney, and mortality benefit of this approach in patients with type 2 diabetes and albuminuria.

Presented at the American Heart Association Scientific Sessions 2023, the study leveraged data from a set of 12 trials examining the agents to estimate the relative effects of combination therapy compared to conventional care in patients with type 2 diabetes and a UACR of 30 mg/g or more. In the study, investigators estimated absolute risk reduction by applying estimated combination treatment effects to participants receiving conventional care in CANVAS and CREDENCE, which were also used in estimating the relative effects of treatment for SGLT2 inhibitors.

Of note, the 2 non-steroidal mineralocorticoid receptor agonist trials were FIDELIO-DKD and FIGARO-DKD. The GLP-1 receptor agonist trials were ELIXA, LEADER, SUSTAIN-6, EXSCEL, Harmony Outcomes, REWIND, PIONEER 6, and AMPLITUDE-O.

Upon analysis, results suggested combination therapy with SGLT2 inhibitors, GLP-1 receptor agonists, and non-steroidal mineralocorticoid receptor antagonist was associated with a 35% reduction in risk of the study’s primary major adverse cardiovascular events endpoint of nonfatal myocardial infarction, nonfatal stroke or cardiovascular death relative to conventional care. Investigators highlighted the corresponding estimated absolute risk reduction over 3 years was 4.4% (95% Confidence Interval [CI], 3.0-5.7), with a number-needed-to-treat of 23 (95% CI, 18-33).

Investigators also pointed out, for a 50-year-old commencing combination therapy, estimated MACE event-free survival was 21.1 years compared to 17.9 years for conventional care (3.2 years gained; 95% CI 2.1-4.3). Projected gains were observed for survival free from heart failure hospitalization (3.2 years; 95% CI, 2.4-4.0), CKD progression (5.5 years; 95% CI, 4.0-6.7), cardiovascular death (2.2 years; 95% CI, 1.2-3.0) and all-cause death (2.4 years; 95% CI, 1.4-3.4).

Additional analysis performed assuming 50% additive effects of combination therapy indicated attenuated, but clinically relevant, gains in event-free survival for major adverse cardiovascular events (2.4 years, 95% CI 1.1-3.5), CKD progression (4.5 years, 95% CI 2.8-5.9), and all-cause mortality (1.8 years, 95% CI 0.7-2.8).

Learn more about the study and how it informs the management of patients with type 2 diabetes, check out our interview with lead investigator Brendon Neuen, MBBS, PhD, nephrologist and director of the Kidney Trials Unit at Royal North Shore Hospital.

Relevant disclosures for Neuen include AstraZeneca, Bayer, Boehringer and Ingelheim, and Janssen.

References:

Neuen BL, Heerspink HJ, Vart P, et al. Estimated Lifetime Cardiovascular, Kidney and Mortality Benefits of Combination Treatment With SGLT2 Inhibitors, GLP-1 Receptor Agonists, and Non-steroidal MRA Compared With Conventional Care in Patients With Type 2 Diabetes and Albuminuria. Paper presented at: American Heart Association Scientific Sessions 2023; November 10 - 13; Philadelphia, PA. Accessed November 12, 2023.