SGLT2 Inhibitors Beneficial for Treating Type 2 Diabetes Mellitus

A duo of drugs have proven effective in treating patients with type 2 diabetes mellitus, while reducing the risk of cardiovascular events.

In a study planned to be presented at the ENDO 2020, a team led by Ali Al-Khazaali, MD, Saint Louis University, evaluated the data to aid in the prescribing decision with regard to treatment with regard to severity of illness and risk of adverse events for patients with type 2 diabetes mellitus.

Cardiovascular outcome trials (CVOT) of glucagon-like peptide-1 receptor agonists (GLP-1 RA), as well as sodium-glucose co-transport 2 inhibitors (SGLT2i) have shown the ability to reduce the risk of major adverse cardiovascular events, cardiovascular deaths, and renal outcomes.

This pair of drugs are commonly used to treat type 2 diabetes with similar ability to reduce major heart complications, including heart attack, stroke, and death from cardiovascular disease.

Past research has shown both classes of drugs have heart and kidney benefits outside of controlling blood sugar.

The investigators conducted a systemic review of the major cardiovascular outcome trials and previous meta-analyses.

Overall, they looked at 6 trials on GLP-1 RA involving 51,762 participants and 4 trials on SGLT2 inhibitors including 33,457 subjects.

Both drug classes reduced major adverse cardiovascular events and cardiovascular deaths when compared to controls.

However, neither treatment option was preferred (comparison GLP1-RA vs. SGLT2i: [Relative rate major adverse cardiovascular events, 1.09; 95% CI, 0.98-1.22; P = 0.129; RR cardiovascular death, 1.04; 95% CI, 0.87-1.24; P = 0.657).

Hospitalization for heart failure improved with the SGLT2i treatment (RR, 0.68; 95% CI, 0.61-0.76; P <0.001), but not with GLP-1 RA (RR, 0.94; 95% CI, 0.86-1.03; P = 0.17).

Overall, the rate of hospitalization for heart failure was 32% less in patients taking the SGLT2 inhibitors when compared to the patients not taking these drugs. This was particularly true for patients with more severe cardiovascular disease risks.

However, patients taking GLP-1 RA drugs did not have a reduced rate of hospitalization for heart failure compared with individuals who had diabetes that were not taking the drugs.

While both classes of drugs demonstrated kidney benefit, neither class was superior.

Both drug classes showed significant reduction in RO (GLP-1 RA, [RR, 0.83; 95% CI, 0.75-0.912; {P <0.001; SGLT2i, RR, 0.067; 95% CI, 0.57-0.79; P = 0.001) without a preferential different between the classes (GLP-1 RA vs SGLT2i, relative difference (RD), 0.005; 95% CI, -0.011-0.021; P = 0.532, number needed to treat (NNT), 200).

The serious adverse events for SGLT2i were mostly mycotic genital infections for women (NNH = 13) and diabetic ketoacidosis (NNH = 595). For the GLP1 RA class, gastrointestinal intolerance was the major serious adverse event (NNH = 35).

“Both GLP-1 RA and SGLT2i classes showed similar reduction in MACE, CVD, and RO.SGLT2i have advantages over GLP-1 RA in reduction in HHF especially in those with more severe cardiovascular disease risk,” the authors wrote.

In a special edition House Call video conference interview with HCPLive®, Muthiah Vaduganathan, a cardiologist at the Center for Advanced Heart Disease at Brigham and Women's Hospital, discussed SGLT2 trial data on the eve of the virtual kickoff for the American College of Cardiology (ACC) 2020 Scientific Sessions.

Vaduganathan projected the most significant trial of this year to be the Empagliflozin Outcome Trial in Patients with Chronic Heart Failure with Reduced Ejection Fraction (EMPEROR-Reduced) trial, in which Boehringer Ingelheim and Eli Lilly and Company are promoting the assessment the SGLT2 inhibitor’s safety and efficacy versus placebo on top of guideline-directed therapy in patients with heart failure with reduced ejection fraction (HFrEF).

Ventures into heart failure subtype care is the next step for the add-on drug class, Vaduganathan said, after showing benefits for cardiovascular risk reduction, glycemic control, and renal outcomes.