What is the standard treatment approach for a patient with type 2 diabetes (T2D)?

Standard Treatment for Type 2 Diabetes

Start with metformin plus lifestyle modifications as first-line therapy, then add an SGLT2 inhibitor or GLP-1 receptor agonist based on the presence of cardiovascular disease, heart failure, or chronic kidney disease. 1

Initial Treatment Approach

Metformin is the foundation of therapy for all patients with type 2 diabetes unless contraindicated, combined with lifestyle interventions including at least 150 minutes per week of physical activity and weight loss targeting 7% of baseline weight. 1, 2, 3

• Early combination therapy at treatment initiation can be considered to shorten time to achieving glycemic goals, rather than waiting for monotherapy failure. 1
• Target HbA1c between 7-8% for most adults, with deintensification if HbA1c falls below 6.5%. 1

Second-Line Agent Selection: Comorbidity-Driven Approach

Patients WITH Cardiovascular or Kidney Disease

Add an SGLT2 inhibitor OR GLP-1 receptor agonist to metformin—these agents reduce mortality and major cardiovascular events beyond glycemic control. 1, 2

For heart failure (reduced or preserved ejection fraction): Use an SGLT2 inhibitor, which reduces HF hospitalizations by 18-25% and provides cardiovascular event reduction. 1

For chronic kidney disease (eGFR 20-60 mL/min/1.73m² or albuminuria): Use an SGLT2 inhibitor to minimize CKD progression (24-39% risk reduction), reduce cardiovascular events, and decrease HF hospitalizations. 1, 2

For advanced CKD (eGFR <30 mL/min/1.73m²): Prefer a GLP-1 receptor agonist due to lower hypoglycemia risk and cardiovascular event reduction, as SGLT2 inhibitor glycemic benefits diminish at eGFR <45. 1

For stroke risk or weight loss goals: Prioritize GLP-1 receptor agonists, which reduce stroke risk by 12-26% and achieve >5% weight loss in most patients (often >10% with high-potency agents or dual GIP/GLP-1 receptor agonists). 1, 2

Patients WITHOUT Cardiovascular or Kidney Disease

Select agents addressing both glycemic and weight goals. 1

• SGLT2 inhibitors and GLP-1 receptor agonists remain preferred over DPP-4 inhibitors, sulfonylureas, or thiazolidinediones due to superior mortality and morbidity outcomes. 1
• Avoid DPP-4 inhibitors as add-on therapy—they do not reduce all-cause mortality or major cardiovascular events despite glycemic efficacy. 1

When to Initiate Insulin

Start insulin immediately if any of the following are present, regardless of background therapy: 1, 4

• Evidence of ongoing catabolism (unexpected weight loss)
• Symptomatic hyperglycemia
• HbA1c >10% (>86 mmol/mol) or blood glucose ≥300 mg/dL (≥16.7 mmol/L)

However, prefer GLP-1 receptor agonists (including dual GIP/GLP-1 receptor agonists) over insulin when both options are viable, due to superior weight and hypoglycemia profiles. 1

• If insulin is necessary, combine it with a GLP-1 receptor agonist for greater glycemic effectiveness, beneficial weight effects, and reduced hypoglycemia risk. 1
• Reassess and reduce insulin dosing when adding or escalating GLP-1 receptor agonist therapy. 1

Insulin Regimens When Required

For severe hyperglycemia requiring insulin: Start basal-bolus therapy at 0.3-0.4 units/kg/day, divided approximately half as basal insulin (long-acting analog) and half as prandial insulin (rapid-acting analog). 4, 5

For conventional insulin initiation: Begin with basal insulin at 10 units once daily or 0.1-0.2 units/kg/day, titrating by 2-4 units every 3 days until fasting glucose reaches 80-130 mg/dL. 5

Continue metformin with insulin to reduce weight gain, lower insulin requirements, and decrease hypoglycemia risk. 4

Medication Adjustments and Monitoring

• Reevaluate medication plans every 3-6 months, adjusting based on glycemic control, weight goals, and metabolic comorbidities. 1
• When adding SGLT2 inhibitors or GLP-1 receptor agonists achieves adequate control, reduce or discontinue sulfonylureas or long-acting insulins due to increased severe hypoglycemia risk. 1
• Self-monitoring of blood glucose may be unnecessary in patients on metformin combined with SGLT2 inhibitors or GLP-1 receptor agonists (not requiring insulin). 1

Common Pitfalls to Avoid

Do not delay insulin in severely hyperglycemic patients—oral agents alone will not achieve control when glucose >300 mg/dL and HbA1c >10%. 4

Do not use sulfonylureas or long-acting insulins as preferred second-line agents—they are inferior to SGLT2 inhibitors and GLP-1 receptor agonists for reducing mortality and morbidity, though they retain limited value for glycemic control. 1

Do not start with basal insulin only in severe hyperglycemia—both basal and prandial coverage are required from the outset to address glucose toxicity. 4

Do not continue sulfonylureas when initiating multiple daily insulin injections—this significantly increases hypoglycemia risk. 4