Anti-Sugar Pills becoming Healthy Hearty Promoters

Bryan Vo, PharmD, Cub Pharmacy

Background: The American Heart Association (AHA) and American College of Cardiology (ACC) have developed new clinical guidelines for chronic coronary disease (CCD) management. The aim of the newly published guidelines is to consolidate the previously published guidelines, “2012 Guideline for the Diagnosis and Management of Patients With Stable Ischemic Heart Disease” and the corresponding “2014 Focused Update of the Guideline for the Diagnosis and Management of Patients With Stable Ischemic Heart Disease,” and to provide updated recommendations with new clinical evidence that has been collected since 2014. The 2023 guideline summarized these updates and reviewed the impact it may have on managing patients with CCD. During the same year ACC published their 2014 guideline, dapagliflozin (Farxiga®) and empagliflozin (Jardiance®) were approved by the FDA for the treatment of patients with diabetes following the first approved sodium-glucose cotransporter 2 (SGLT2) inhibitor, canagliflozin (Invokana®) in 2013. 

Evidence: SGLT2 inhibitors were intended to improve patients’ glucose levels by increasing glucose excretion. Since 2014, evidence has shown that SGLT2 inhibitors can provide benefits to patients with cardiovascular complications, including coronary disease.

An article from Petrie et al. concluded that dapagliflozin significantly reduced the risk of worsening heart failure or cardiovascular death (primary outcome), independently of diabetic status. The authors found that patients without diabetes, the primary outcome occurred in 171 of 1298 (13.2%) in the dapagliflozin group and 231 of 1307 (17.7%) in the placebo group (hazard ratio, 0.73; 95% CI, 0.60 to 0.88). 

The 2023 AHA/ACC guidelines now address the management of comorbidities, including hypertension, diabetes, and obesity. The 2023 AHA/ACC guidelines emphasized that in patients with CCD and heart failure with LVEF ≤40%, SGLT2 inhibitors may reduce the risk of cardiovascular and heart failure hospitalization and may improve quality of life, irrespective of the patients’ diabetic status. Moreover, the use of SGLT2 inhibitors provides additional benefits to weight loss and kidney disease. 

Discussion/Clinical Impact: The effect of using SGLT2 inhibitors in patients with CCD and heart failure demonstrated great clinical impact. It is also important to assess if the use of SGLT2 inhibitors are cost-effective for patients. In the 2023 AHA/ACC guidelines, it was commented that for patients with reduced ejection fraction (HFrEF), the use of SGLT2 inhibitors has an immediate value ($50,000 to <$150,000 per quality-adjusted life year (QALY) gained). The QALY describes the cost associated with the health benefits for a quality life that the patient gained. The 2023 AHA/ACC guidelines noted that additional clinical studies are needed to conclude the value of SGLT2 inhibitors in patients with CCD and heart failure with preserved ejection fraction (HFpEF). The reduction in cardiovascular mortality was not statistically significant in the EMPEROR-PRESERVED or DELIVER trials, or in a pooled analysis of the two trials for the use of SGLT2 inhibitors. Therefore, the use of SGLT2 inhibitors in patients with HFpEF is considered low value, and it is not cost effective.

An article from Aggarwal et al. described an estimated national total spending on SGLT2 inhibitors of $3,308,539,528 (95% CI, $2,722,122,074–$3,894,956,982). The findings for out-of-pocket spending that were statistically significant were for individuals having Medicaid ($5.10 ($0.34 to $9.86), P=0.001) or Medicaid and Medicare ($3.87 ($1.00 to $6.75), P=0.001). Patients with private insurance had an average out-of-pocket cost of $49.34 (P=1.00). The out-of-pocket cost remains high compared to other alternative drugs for CCD management. This cost factor may be a barrier to patients that need additional help, but have no resources to acquire the drugs. However, for patients that can afford the drugs, SGLT2 inhibitor use is recommended.

Zannad et al. commented that there were no serious adverse events reported with the use of SGLT2 inhibitors. SGLT2 inhibitors should be part of the standard of care treatment options for patients with CCD and heart failure. These agents provide benefits in many different aspects for patients – weight loss, cardiovascular health, and diabetes.

Teaser Summary: The 2023 AHA/ACC Clinical Guideline for Chronic Coronary Disease (CCD) provides new medication recommendations with emerging evidence. What benefits do SGLT2 inhibitors provide to patients with CCD?


  1. Virani SS, Newby LK, Arnold SV, et al. 2023 AHA/ACC/ACCP/ASPC/NLA/PCNA Guideline for the management of patients with chronic coronary disease: A report of the American Heart Association/American College of Cardiology Joint Committee on Clinical Practice Guidelines [published online ahead of print, 2023 Jul 20]. Circulation. 2023;10.1161/CIR.0000000000001168. doi:10.1161/CIR.0000000000001168
  2. Petrie MC, Verma S, Docherty KF, et al. Effect of dapagliflozin on worsening heart failure and cardiovascular death in patients with heart failure with and without diabetes [published correction appears in JAMA. 2021 Apr 6;325(13):1335]. JAMA. 2020;323(14):1353-1368. doi:10.1001/jama.2020.1906
  3. Aggarwal R, Vaduganathan M, Chiu N, Bhatt DL. Out-of-pocket costs for SGLT-2 (sodium-glucose transport protein-2) inhibitors in the United States. Circ Heart Fail. 2022;15(3): e009099. doi:10.1161/CIRCHEARTFAILURE.121.009099

Zannad  F,  Ferreira  JP,  Pocock  SJ,  et  al.  SGLT2  inhibitors  in patients with heart failure with reduced ejection fraction: a meta-analysis of the EMPER-OR-Reduced and DAPA-HF trials. Lancet. 2020; 396:819–829.