• Metformin is the preferred initial pharmacologic agent for the treatment of type 2 diabetes.  Once initiated, metformin should be continued as long as it is tolerated and not contraindicated. 

• If the A1C target is not achieved after approximately 3 months, metformin can be combined with any one of the preferred six treatment options: Sulfonylurea (Gliclazide, Glimepiride), Thiazolidinedione (Pioglitazone), DPP-4 inhibitor (Sitagliptin, Vildagliptin, Saxagliptin, Linagliptin), SGLT2 inhibitor (Dapagliflozin, Canagliflozin, Empagliflozin), GLP-1 RA (Liraglutide, Trelagliptin)

OR

Basal insulin (Glargine, Detemir, Degludec) ; the choice of which agent to add is based on drug-specific effects and patient factors.

Note: Consider initiating dual therapy in patients with newly diagnosed type 2 diabetes who have A1C ≥1.5% (12.5 mmol/mol) above their glycemic target.

• The early introduction of insulin should be considered if there is evidence of ongoing catabolism (weight loss), if symptoms of hyperglycemia are present, or when A1C levels (>10% [86 mmol/mol]) or blood glucose levels (≥300 mg/dL [16.7 mmol/L]) are very high.
• Control of fasting glucose can be achieved with human NPH insulin (Insulin Human N) or a Long-acting insulin analog (Glargine, Detemir, Degludec). Many individuals with type 2 diabetes require doses of insulin (Prandial insulin like Insulin Human R, Aspart, Lispro, Glulisine) before meals, in addition to basal insulin, to reach glycemic targets.

• Among patients with type 2 diabetes who have established atherosclerotic cardiovascular disease, established kidney disease, or heart failure, a sodium–glucose co-transporter 2 inhibitor or glucagon-like peptide 1 receptor agonist with demonstrated cardiovascular disease are preferred. 

Lifestyle modifications that improve health should be emphasized along with any pharmacologic therapy.

The American Diabetes Association/European Association recommend a patient-centered approach to choosing appropriate pharmacologic treatment of blood glucose.

• This includes consideration of efficacy and key patient factors:

1) important comorbidities such as atherosclerotic cardiovascular disease (ASCVD) and indicators of high ASCVD risk, chronic kidney disease (CKD), and heart failure.

2) hypoglycemia risk,

3) effects on body weight,

4) side effects,

5) cost, and

6) patient preferences.

• Intensification of treatment for patients with type 2 diabetes not meeting treatment goals should not be delayed.
• The medication regimen should be reevaluated at regular intervals (every 3–6 months) and adjusted as needed to incorporate new patient factors.

American Diabetes Association.  Pharmacologic approaches to glycemic treatment: Standards of Medical Care in Diabetes—2021. Diabetes Care 2021; 44(Suppl. 1): S98–S111 

https://care.diabetesjournals.org/content/44/Supplement_1/   

https://www.diabetes.org/a1c/diagnosis  

   Note: For informational purposes only. Consult your textbook for advising your patients.