Overlap of SGLT2 Inhibitors from Diabetology to Cardiology
As recent research shows, one of the modern groups of antidiabetic drugs - SGLT2 inhibitors, also known as gliflozins - brings benefits not only in diabetology but also in cardiology and nephrology. It has been confirmed that representatives of this class of drugs prolong patients' lives, reduce the incidence of major cardiovascular (CV) events and the risk of heart failure (HF), and improve renal function. A recently published study additionally indicates that the CV benefit of empagliflozin is independent of the number of compensated CV risk factors and manifests within the first 3 months of treatment.
Impact on SGLT2i reducing overall mortality
A meta-analysis of randomized controlled trials published this year confirmed that sodium-glucose cotransporter 2 inhibitors (SGLT2i) reduce overall mortality in patients with type 2 diabetes. This meta-analysis included 21 studies with a total of 39,593 patients using one of the SGLT2i and 30,771 with a comparator (active treatment or placebo). Studies with a duration of at least 52 weeks, enrolling at least 100 patients in each arm, were analyzed. The median follow-up duration in these studies was 104 weeks. Treatment with SGLT2i was associated with a significant relative reduction in overall mortality by 14% (Mantel-Haenszel odds ratio [MH-OR] 0.86; 95% confidence interval [CI] 0.81–0.91; p < 0.00001). No significant heterogeneity was found between the studies.
Improvement in heart failure-related outcomes
The main cause of death in patients with type 2 diabetes is cardiovascular disease. They are also a cause of significant morbidity in these patients. SGLT2i have demonstrated not only their cardiovascular safety but also cardiovascular benefit. The EMPA-REG OUTCOME study with empagliflozin demonstrated a reduction in cardiovascular mortality and hospitalization for HF in patients with type 2 diabetes and known cardiovascular disease over 3 years of treatment. A new analysis of data from this study further showed that empagliflozin's benefit manifests soon after the initiation of therapy. Glycated hemoglobin (HbA1c), systolic blood pressure (SBP), body weight, risk of hospitalization for HF, hospitalization for HF or death from cardiovascular causes, and hospitalization for HF or death from any cause significantly decreased with empagliflozin treatment compared to placebo after just 12 weeks. The metabolic and clinical benefits of empagliflozin persisted for 6 and 12 months after randomization and were independent of the presence of HF at the start of treatment.
Overall cardiovascular benefit
Another analysis of data from the EMPA-REG OUTCOME study evaluated the cardiovascular benefit of empagliflozin based on achieving 7 goals for compensating cardiovascular risk factors:
- HbA1c < 58.5 mmol/mol (< 5.9%)
- LDL cholesterol < 2.59 mmol/l or use of statin
- SBP < 140 mmHg and DBP < 90 mmHg
- use of renin-angiotensin-aldosterone system (RAAS) blockers
- normoalbuminuria
- use of acetylsalicylic acid (ASA)
- non-smoking
In the placebo group, achieving 0–3 or 4–5 of these goals was associated with significantly higher cardiovascular mortality, a higher risk of hospitalization for HF or death from cardiovascular causes (excluding stroke [CVA]), and a higher risk of nonfatal myocardial infarction, nonfatal CVA, and death from cardiovascular causes (MACE) compared to achieving 6–7 goals. Empagliflozin significantly reduced the risk of all these parameters compared to placebo in all categories of cardiovascular risk factor compensation, i.e., with compensation for 0–3, 4–5, and 6–7 cardiovascular risk factors.
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Sources:
1. Silverii G. A., Monami M., Mannucci E. Sodium-glucose co-transporter-2 inhibitors and all-cause mortality: a meta-analysis of randomized controlled trials. Diabetes Obes Metab 2021 Apr; 23 (4): 1052–1056, doi: 10.1111/dom.14286.
2. Pellicori P., Ofstad A. P., Fitchett D. H. et al. Early benefits of empagliflozin in patients with or without heart failure: findings from EMPA-REG OUTCOME. ESC Heart Fail 2020 Sep 11; 7 (6): 3401–3407, doi: 10.1002/ehf2.12891.
3. Inzucchi S. E., Khunti K., Fitchett D. H. et al. Cardiovascular benefit of empagliflozin across the spectrum of cardiovascular risk factor control in the EMPA-REG OUTCOME trial. J Clin Endocrinol Metab 2020 Sep 1; 105 (9): 3025–3035, doi: 10.1210/clinem/dgaa321.
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