Type 2 Diabetes: High-Risk Indicators & Therapy

• First-line therapy involves Metformin and Comprehensive Lifestyle, which includes weight management and physical activity.
• Consider independently of baseline A1C, individualized A1C target or Metformin use.

Indicators of High-Risk

• High-risk indicators include established ASCVD (atherosclerotic cardiovascular disease), CKD (chronic kidney disease), or HF (heart failure).
• ASCVD indicators of high-risk include age 255 years with coronary, carotid, or lower-extremity artery stenosis >50%, or LVH (left ventricular hypertrophy).
• HF, particularly HFrEF (heart failure with reduced ejection fraction) defined as LVEF <45%.

If A1C Above Individualized Target

• If A1C is above the individualized target, proceed as follows.
• For compelling needs to minimize hypoglycemia, the options include DPP-4i, GLP-1 RA, SGLT2i, or TZD.
• For compelling needs to minimize weight gain or promote weight loss, the options include GLP-1 RA with good efficacy for weight loss.
• When cost is a major issue, consider SU or TZD.
• SGLT2i are preferable with primary evidence of reducing CKD progression.
• GLP-1 RA with proven CVD benefit if SGLT2i is not tolerated or contraindicated.
• SGLT21 with evidence of reducing CKD progression in CVOTS is preferable
• For patients with T2D and CKD with eGFR <60 mL/min/1.73 m² and at increased risk of cardiovascular events, consider the addition of SU or basal insulin.

Further Actions

• If further intensification is required or the patient cannot tolerate GLP-1 RA and/or SGLT2i, choose agents demonstrating CV benefit and/or safety.
• For patients on GLP-1 RA, consider adding SGLT2i with proven CVD benefit and vice versa.
• If quadruple therapy is required, or SGLT2i and/or GLP-1 RA not tolerated or contraindicated, use a regimen with the lowest risk of weight gain.
• If DPP-4i is not tolerated or contraindicated or patient already on GLP-1 RA, add SU, TZD or Basal insulin cautiously.
• Sulphonylureas and TZDs are considered if the A1C level is still above the target
• Consider the addition of SU or basal insulin
• Later generation SU with is preferred to lower the risk of hypoglycemia
• Action whenever new clinical considerations come up, regardless of background glucose-lowering medications.
• Most patients in relevant trials were on Metformin at baseline as glucose-lowering therapy
• Proven CVD benefit means it has label indication of reducing CVD events