Meta-Analysis Explores Cardiovascular, Renal Effects of SGLT2s and GLP-1s

A new meta-analysis of data from placebo-controlled randomized trials is diving deeper into the potential cardiovascular benefits of antidiabetes drugs in the glucagon-like peptide-1 receptor agonists (GLP-1 RAs) and sodium-dependent glucose cotransporter-2 (SGLT2) inhibitors.

Carried out by investigators from the Capital Medical University in Beijing, China, the hope of the study was to provide further details and information for incorporating into the design of future trials.

A rapidly evolving area of cardiometabolic health, investigators hoped to provide clinicians and researchers with an update to a pair of previous meta-analyses examining outcome trials of the respective classes—Investigators listed 4 specific aims of their study.

These objectives were to update earlier published estimates of benefit or harms associated with these drug classes in patients with type 2 diabetes with endpoints for major adverse cardiovascular events (MACE) or chronic kidney disease, to compute the number needed to treat for 1 year to prevent 1 endpoint, to assess the antihypertensive effects of these classes in trials applying 24-hour ambulatory blood pressure monitoring, and to meta-regress treatment effects associated with GLP-1 RAs and SGLT2 inhibitors in patients with type 2 diabetes.

Using the PubMed and EMBASE databases, investigators identified 2 trials examining the effects of liraglutide and 7 trials examining the effects of SGLT2 inhibitors on glycemic control and 24-hour blood pressure. Additionally, investigators identified 7 studies for their analysis examining outcomes with GLP-1 RA and 5 studies for their analysis examining outcomes with SGLT2 inhibitors.

In total, 2238 patients were identified in the 7 trials examining SGLT2 inhibitors and 24-hour blood pressure. In these trials, SGLT2 inhibitor use was associated with a lowered 24-hour systolic and diastolic blood pressures with a mean reduction of 4.4/1.9 mmHg (95% CI, 3.4-5.5/1.2-2.6 mmHg). Conversely, analysis of the 2 trials examining the effects of liraglutide yield contradictory results.

In 5 trials examining outcomes with SGLT2 inhibitors, investigators obtained data related to 43,467 patients with a follow-up time of 1.5-4.2 years. in aggregate analyses, SGLT2 inhibitor use was associated with a 13% reduction in MACE (HR, 0.87; 95% CI, 0.82-0.93). Additional results from the analyses indicated SGLT2 inhibitor use was associated with a 32% reduction in heart failure (HR, 0.68; 95% CI, 0.62-0.75), an 18% reduction in cardiovascular death (HR, 0.82; 95% CI, 0.72-0.93), a 13% reduction in myocardial infarction (HR, 0.87; 95% CI, 0.79–0.96), and a 39% reduction in worsening chronic kidney disease (HR, 0.61; 95% CI, 0.56-0.67).

From GLP-1 RA outcome trials, investigators obtained data related to 56,004 patients with a follow-up time of 1.3-5.4 years. In aggregated analyses, GLP-1 RA use was associated with a 12% (HR, 0.88; 95% CI, 0.84-0.93) reduction in MACE. For chronic kidney disease, aggregate analyses indicated a reduction in risk of 16% (HR, 0.84; 95% CI, 0.74-0.89). Investigators also pointed out reductions for individual MACE components aged from 10-16% (P<.01).

Further analysis yielded additional information in regard to the potential effects of GLP1-RA and SGLT2 inhibitor use. Specific results highlighted by investigators the trend of lower blood pressure being associated with additional reductions in risk of heart failure and chronic kidney disease, but not MACE. Additionally, investigators pointed out stricter glycemic control was associated with higher heart failure risk but this was unrelated to risk of MACE or CKD.

“Both GLP1-RAs and SGLT2-Is reduced BP, improved glycemic control without weight gain, and prevented cardiovascular and renal complications in high-risk T2DM patients,” wrote study investigators. “These observations hold promise for the use of these drugs as first-line agents in patients to prevent rather than treat established cardiovascular or renal disease.”

This study, “Opportunities of Antidiabetic Drugs in Cardiovascular Medicine,” was published in Hypertension.