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TABLE 1

Comparison of Recent Pharmacologic Therapy Algorithms for Glycemic Management in Type 2 Diabetes

RecommendationADA (36)AACE/ACE (42)ESC (43)ACC/AHA (CVD Primary Prevention) (44)ACC (CVD Secondary Prevention) (45)
Metformin as first-line therapy in patients with no CVD, CHF, or CKD Yes Yes Yes Yes NA 
Metformin as first-line therapy in patients with CVD, CHF, or CKD Yes* No No NA No 
Primary prevention: high-risk patients with multiple risk factors but without overt CVD, CKD, or HF Metformin* SGLT2 inhibitor or long-acting GLP-1 receptor agonist SGLT2 inhibitor or GLP-1 receptor agonist if high risk of HF; GLP-1 receptor agonist if high risk of CVD SGLT2 inhibitor or GLP-1 receptor agonist added to metformin if CVD risk factors and A1C ≥7% SGLT2 inhibitor if high risk of CVD, CKD, or HF; GLP-1 receptor agonist if high risk of CVD 
With comorbidities      
CVD SGLT2 inhibitor or GLP-1 receptor agonist SGLT2 inhibitor or long-acting GLP-1 receptor agonist SGLT2 inhibitor or GLP-1 receptor agonist NA SGLT2 inhibitor or GLP-1 receptor agonist 
HFrEF SGLT2 inhibitor SGLT2 inhibitor SGLT2 inhibitor NA SGLT2 inhibitor 
CKD with albuminuria SGLT2 inhibitor SGLT2 inhibitor SGLT2 inhibitor or GLP-1 receptor agonist NA SGLT2 inhibitor 
CKD without albuminuria SGLT2 inhibitor or GLP-1 receptor agonist SGLT2 inhibitor SGLT2 inhibitor or GLP-1 receptor agonist NA SGLT2 inhibitor 
RecommendationADA (36)AACE/ACE (42)ESC (43)ACC/AHA (CVD Primary Prevention) (44)ACC (CVD Secondary Prevention) (45)
Metformin as first-line therapy in patients with no CVD, CHF, or CKD Yes Yes Yes Yes NA 
Metformin as first-line therapy in patients with CVD, CHF, or CKD Yes* No No NA No 
Primary prevention: high-risk patients with multiple risk factors but without overt CVD, CKD, or HF Metformin* SGLT2 inhibitor or long-acting GLP-1 receptor agonist SGLT2 inhibitor or GLP-1 receptor agonist if high risk of HF; GLP-1 receptor agonist if high risk of CVD SGLT2 inhibitor or GLP-1 receptor agonist added to metformin if CVD risk factors and A1C ≥7% SGLT2 inhibitor if high risk of CVD, CKD, or HF; GLP-1 receptor agonist if high risk of CVD 
With comorbidities      
CVD SGLT2 inhibitor or GLP-1 receptor agonist SGLT2 inhibitor or long-acting GLP-1 receptor agonist SGLT2 inhibitor or GLP-1 receptor agonist NA SGLT2 inhibitor or GLP-1 receptor agonist 
HFrEF SGLT2 inhibitor SGLT2 inhibitor SGLT2 inhibitor NA SGLT2 inhibitor 
CKD with albuminuria SGLT2 inhibitor SGLT2 inhibitor SGLT2 inhibitor or GLP-1 receptor agonist NA SGLT2 inhibitor 
CKD without albuminuria SGLT2 inhibitor or GLP-1 receptor agonist SGLT2 inhibitor SGLT2 inhibitor or GLP-1 receptor agonist NA SGLT2 inhibitor 
*

Metformin is considered initial therapy, but additional and/or alternative agents may be considered in special circumstances, such as in individuals with established or increased risk of cardiovascular or renal complications. Addition is irrespective of A1C on metformin.

Only the ADA/EASD algorithm separates out CKD with or without albuminuria. The ACC algorithm states that, if eGFR is <30 mL/min/1.73 m2, consider a GLP-1 receptor agonist.

SGLT2 inhibitors (empagliflozin, canagliflozin, or dapagliflozin) have class 1, level B, recommendation for CKD, whereas GLP-1 receptor agonists (liraglutide or semaglutide) have a class 2a, level B, recommendation. NA, not applicable.

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