Glucagon-like peptide-1 receptor agonists (GLP-1 RA) and sodium-glucose co-transporter 2 inhibitors (SGLT2i ), which are commonly used to treat type 2 diabetes mellitus (T2DM) are similar in their ability to reduce major heart complications, including heart attack, stroke and death from cardiovascular disease. These findings were accepted for presentation at the Endocrine Society’s Annual Meeting 2020 (ENDO 2020).1,2
Cardiovascular outcome trials (CVOTs) of GLP-1 RA and SGLT2i have demonstrated reduction of major adverse cardiovascular events (MACE), cardiovascular deaths (CVD) and renal outcomes (RO). Further evaluation of data from CVOTs can benefit the treatment decisions with regards to the severity of illness and risk of adverse events.1,2
The investigators have conducted a systemic review of major CVOTs and previous meta-analyses and analyzed data from six previous trials of GLP-1 RA comprising of 51,762 subjects and four trials of SLGT2 inhibitors that included 33,457 subjects. Both drug classes showed similar effects in reducing combined MACE such as heart attack, stroke and death from cardiovascular disease, compared to patients with T2DM who were not taking the drugs.1,2
The rate of hospitalization for heart failure was 32% less in T2DM patients taking SGLT2i compared to patients who were not taking SGLT2i, particularly in those with more severe cardiovascular disease risk. In contrast, T2DM patients taking GLP-1 RA did not have a reduced rate of hospitalization for heart failure compared with people who were not taking GLP-1 RA. Both classes of drugs demonstrated kidney benefit and neither class was superior.1,2
Existing meta-analyses also support the findings of the current analysis. Meta-analysis of 4 earlier trials of LEADER, ELIXA, SUSTAIN-6, and EXCEL found improvements in MACE when compared to controls. Subsequently, when the data from HARMONY was added to the analysis, the benefits of the GLP-1 RA class of drug with regards to MACE and cardiovascular deaths were confirmed. They proposed that although GLP-1 RA reduced the risk of worsening renal failure, this class was inferior to the results of SGLT2i class. However, no formal comparison was given. Furthermore, EMPA-REG, CANVAS and DECLARE trials confirmed that these drugs reduced MACE and heart failure hospitalization.
The most common serious side effects for SGLT2 inhibitors included yeast infections in women and diabetic ketoacidosis, a rare life-threatening problem that can affect people with diabetes. The major serious side effect for GLP-1 RA drugs was gastric distubance.1,2 “Doctors need to balance this side effect against the possible weight-loss benefits of these medicines,” investigators stated.1
Additionally, the investigators suggest modifying the current American Diabetes Association recommendations to guide clinicians towards the use of either GLP-1 RA or SGLT2i for patients with T2DM and higher cardiovascular risk, but preferentially encourage the use of SGLT2i for those with heart failure and more advanced cardiovascular disease. The CREDENCE trial demonstrated that SGLT2i had theoretical benefits of renal protection, which thus provided sufficient evidence for it to be approved by the United States Food and Drug Administration. Only the LEADER and REWIND trials prospectively adjudicated renal events. Although there was no preferential benefit of SGLT2i class compared to GLP-1 RA class for renal protection, the 2 classes of drugs need to be analyzed either in head-to-head trials, or retrospectively to evaluate the effects on renal events.3
Both GLP-1 RA and SGLT2i classes showed similar reduction in MACE, CVD and RO. SGLT2i have advantages over GLP-1 RA in the reduction of hospitalization for heart failure especially in those with more severe cardiovascular disease risk.3