SGLT-2 inhibitors reduce cardiac events, mortality compared to DPP-4 inhibitors

Sodium-glucose cotransporter-2 (SGLT-2) inhibitors reduced risk of major adverse cardiovascular events (MACEs), hospitalizations for heart failure, and risk for acute kidney injury versus dipeptidyl peptidase-4 (DPP-4) inhibitors but also increased risk of genital infections and diabetic ketoacidosis, a recent comparison found.

Researchers studied 144,614 commercially insured adults who were initiating therapy with an SGLT-2 inhibitor or a DPP-4 inhibitor. The primary outcomes were MACE, a composite of myocardial infarction, stroke, or all-cause death, and hospitalization for heart failure. Safety outcomes were hypovolemia, fractures, falls, genital infections, diabetic ketoacidosis, acute kidney injury, and lower-limb amputation. Results were published Feb. 6 by JAMA Internal Medicine.

In the cohort, 44,099 patients had a baseline HbA1c level of less than 7.5%, another 52,986 had an HbA1c level between 7.5% and 9%, and 47,529 had a baseline level greater than 9%. Overall, 87,274 eligible patients were propensity score-matched: 24,052 with HbA1c levels less than 7.5%; 32,290 with HbA1c levels between 7.5% and 9%; and 30,932 with HbA1c levels greater than 9%.

Over a mean follow-up of eight months, SGLT-2 inhibitors were associated with a lower rate of MACE (incidence rates [IRs] per 1,000 person-years, 17.13 vs. 20.18; hazard ratio [HR], 0.85 [95% CI, 0.75 to 0.95]; rate difference [RD], −3.02 [95% CI, −5.23 to –0.80]) and of hospitalization for heart failure (IR per 1,000 person-years, 3.68 vs. 8.08; HR, 0.46 [95% CI, 0.35 to 0.57]; RD, −4.37 [95% CI, −5.62 to −3.12]). There were no overall differences between treatments for the risk of myocardial infarction (HR, 0.92; 95% CI, 0.74 to 1.09) or stroke (HR, 0.86; 95% CI, 0.65 to 1.08). SGLT-2 inhibitors were associated with a significantly reduced risk of all-cause mortality: a HR of 0.74 (95% CI, 0.59 to 0.88) or two fewer deaths per 1,000 person-years.

SGLT-2 inhibitors were also associated with an increased risk of genital infections and diabetic ketoacidosis and a reduced risk of acute kidney injury compared to DPP-4 inhibitors. The findings were consistent by HbA1c level, except for a more pronounced risk of genital infections associated with SGLT-2 inhibitors for HbA1c levels of 7.5% to 9% (IR per 1,000 person-years, 68.5 vs. 22.8; HR, 3.10 [95% CI, 2.68 to 3.58]; RD, 46.22 [95% CI, 40.54 to 51.90]).

“This study complements the evidence provided by [cardiovascular outcome trials] by showing that patients with [type 2 diabetes] can benefit from the use of [SGLT-2 inhibitors] regardless of glycemic control, with no additional increase in the risk of adverse effects in patients with above-target or elevated HbA1c levels, compared with [DPP-4 inhibitor] initiators with similar glycemic control,” the authors wrote.