TY - JOUR
T1 - Effects of sacubitril/valsartan on glycemia in patients with diabetes and heart failure
T2 - the PARAGON-HF and PARADIGM-HF trials
AU - Wijkman, Magnus O
AU - Claggett, Brian
AU - Vaduganathan, Muthiah
AU - Cunningham, Jonathan W
AU - Rørth, Rasmus
AU - Jackson, Alice
AU - Packer, Milton
AU - Zile, Michael
AU - Rouleau, Jean
AU - Swedberg, Karl
AU - Lefkowitz, Martin
AU - Shah, Sanjiv J
AU - Pfeffer, Marc A
AU - McMurray, John J V
AU - Solomon, Scott D
N1 - © 2022. The Author(s).
PY - 2022/6/18
Y1 - 2022/6/18
N2 - BACKGROUND: Compared with enalapril, sacubitril/valsartan lowered HbA1c and reduced new insulin therapy in patients with heart failure with reduced ejection fraction (HFrEF) and diabetes in the PARADIGM-HF trial. We sought to assess the glycemic effects of sacubitril/valsartan in heart failure with preserved ejection fraction (HFpEF) and diabetes, and across the spectrum of left ventricular ejection fraction (LVEF) in heart failure and diabetes.METHODS: We compared the effect of sacubitril/valsartan, relative to valsartan, on HbA1c, new insulin therapy and hypoglycemia in the randomized controlled trial PARAGON-HF, and performed pooled analyses of PARAGON-HF and PARADIGM-HF.RESULTS: Among 2395 patients with HFpEF and diabetes in PARAGON-HF, sacubitril/valsartan compared with valsartan reduced HbA1c (baseline-adjusted between-group difference in HbA1c change at 48 weeks: - 0.24%, 95% CI - 0.33 to - 0.16%, P < 0.001). Numerically, new insulin treatment was initiated less often in the sacubitril/valsartan group than in the valsartan group, but the difference was not statistically significant (12.8% vs. 16.1%; HR: 0.80, 95% CI 0.62-1.02, P = 0.07). Hypoglycemia adverse event reports were low, but more frequent in those receiving sacubitril/valsartan than in the valsartan group (4.2% vs. 2.6%; HR: 1.64, 95% CI 1.05-2.56, P = 0.030). In a pooled analysis of PARAGON-HF and PARADIGM-HF, the effect of sacubitril/valsartan on change in HbA1c was not significantly modified by LVEF (Pinteraction = 0.56). Across the spectrum of LVEF, sacubitril/valsartan reduced new insulin therapy (HR: 0.75, 95% CI 0.63-0.89, P = 0.001), compared with enalapril or valsartan.CONCLUSIONS: Sacubitril/valsartan reduced HbA1c and new insulin therapy in patients with heart failure and diabetes across the spectrum of LVEF but may be associated with a slightly higher risk for hypoglycemia. Trial registration ClinicalTrials.gov NCT01920711.
AB - BACKGROUND: Compared with enalapril, sacubitril/valsartan lowered HbA1c and reduced new insulin therapy in patients with heart failure with reduced ejection fraction (HFrEF) and diabetes in the PARADIGM-HF trial. We sought to assess the glycemic effects of sacubitril/valsartan in heart failure with preserved ejection fraction (HFpEF) and diabetes, and across the spectrum of left ventricular ejection fraction (LVEF) in heart failure and diabetes.METHODS: We compared the effect of sacubitril/valsartan, relative to valsartan, on HbA1c, new insulin therapy and hypoglycemia in the randomized controlled trial PARAGON-HF, and performed pooled analyses of PARAGON-HF and PARADIGM-HF.RESULTS: Among 2395 patients with HFpEF and diabetes in PARAGON-HF, sacubitril/valsartan compared with valsartan reduced HbA1c (baseline-adjusted between-group difference in HbA1c change at 48 weeks: - 0.24%, 95% CI - 0.33 to - 0.16%, P < 0.001). Numerically, new insulin treatment was initiated less often in the sacubitril/valsartan group than in the valsartan group, but the difference was not statistically significant (12.8% vs. 16.1%; HR: 0.80, 95% CI 0.62-1.02, P = 0.07). Hypoglycemia adverse event reports were low, but more frequent in those receiving sacubitril/valsartan than in the valsartan group (4.2% vs. 2.6%; HR: 1.64, 95% CI 1.05-2.56, P = 0.030). In a pooled analysis of PARAGON-HF and PARADIGM-HF, the effect of sacubitril/valsartan on change in HbA1c was not significantly modified by LVEF (Pinteraction = 0.56). Across the spectrum of LVEF, sacubitril/valsartan reduced new insulin therapy (HR: 0.75, 95% CI 0.63-0.89, P = 0.001), compared with enalapril or valsartan.CONCLUSIONS: Sacubitril/valsartan reduced HbA1c and new insulin therapy in patients with heart failure and diabetes across the spectrum of LVEF but may be associated with a slightly higher risk for hypoglycemia. Trial registration ClinicalTrials.gov NCT01920711.
KW - Aminobutyrates/adverse effects
KW - Angiotensin Receptor Antagonists/adverse effects
KW - Biphenyl Compounds/adverse effects
KW - Blood Glucose
KW - Diabetes Mellitus/chemically induced
KW - Enalapril/adverse effects
KW - Glycated Hemoglobin A
KW - Heart Failure/chemically induced
KW - Humans
KW - Hypoglycemia/chemically induced
KW - Insulins/pharmacology
KW - Stroke Volume
KW - Tetrazoles/adverse effects
KW - Valsartan/adverse effects
KW - Ventricular Function, Left
UR - http://www.scopus.com/inward/record.url?scp=85132100863&partnerID=8YFLogxK
U2 - 10.1186/s12933-022-01545-1
DO - 10.1186/s12933-022-01545-1
M3 - Journal article
C2 - 35717169
SN - 1475-2840
VL - 21
JO - Cardiovascular Diabetology
JF - Cardiovascular Diabetology
IS - 1
M1 - 110
ER -