What are the standards of care for a patient with type 2 diabetes?

Standards of Care for Type 2 Diabetes

Start metformin at diagnosis (unless contraindicated) combined with comprehensive lifestyle modification, then add agents with proven cardiovascular and renal benefits—specifically SGLT2 inhibitors or GLP-1 receptor agonists—based on comorbidities rather than waiting for glycemic failure. 1

Initial Pharmacologic Therapy

• Metformin is the preferred first-line agent and should be started at the time of type 2 diabetes diagnosis at 500 mg once or twice daily with meals, titrating to 2000-2550 mg daily as tolerated 1, 2
• Metformin provides established efficacy (HbA1c reduction ~1.0-1.5%), cardiovascular benefits, low cost, and should be continued indefinitely unless contraindicated or not tolerated 1
• Metformin can be safely used when eGFR ≥30 mL/min/1.73 m² (FDA-approved), with dose reduction to 1000 mg/day when eGFR is 45-60 mL/min/1.73 m² 1, 3
• Monitor for vitamin B12 deficiency with long-term metformin use, particularly if anemia or neuropathy develops 1, 2

Comorbidity-Driven Treatment Selection (Independent of HbA1c)

For patients with established atherosclerotic cardiovascular disease, heart failure, chronic kidney disease (eGFR <60 mL/min/1.73 m²), or high cardiovascular risk:

• Add an SGLT2 inhibitor or GLP-1 receptor agonist with demonstrated cardiovascular benefit immediately, regardless of baseline HbA1c and independent of metformin use 1
• SGLT2 inhibitors (canagliflozin, dapagliflozin, empagliflozin) reduce atherosclerotic cardiovascular disease risk by 12-26%, heart failure risk by 18-25%, and kidney disease progression by 24-39% over 2-5 years 3, 4
• GLP-1 receptor agonists are preferred over insulin when greater glucose lowering is needed, providing HbA1c reduction of 1.0-1.5% with cardiovascular benefits and weight loss 1, 4
• High-potency GLP-1 receptor agonists and dual GIP/GLP-1 receptor agonists produce weight loss >5% in most patients, often exceeding 10% 4

Glycemic Targets

• HbA1c target <7.0% for most adults to reduce microvascular complications (retinopathy, nephropathy) by 3.5% absolute risk and myocardial infarction by 3.3-6.2% 1, 4
• Preprandial plasma glucose 90-130 mg/dL (5.0-7.2 mmol/L) 1
• Peak postprandial plasma glucose <180 mg/dL (<10.0 mmol/L) 1, 5
• Blood pressure <130/80 mmHg 1

Treatment Intensification Algorithm

If HbA1c remains ≥7% after 3 months on metformin monotherapy:

• Add a second agent based on patient-specific factors: cardiovascular/renal comorbidities, hypoglycemia risk, weight impact, cost, and patient preferences 1
• Options include: SGLT2 inhibitor, GLP-1 receptor agonist, DPP-4 inhibitor, sulfonylurea, TZD, or basal insulin 1
• Do not delay treatment intensification—advance therapy promptly if targets are not met after 3 months 1, 2

If HbA1c remains ≥7% after 3 months on dual therapy:

• Add a third agent with complementary mechanism of action while maintaining metformin (if tolerated) 1, 2

Exception—Immediate intensive therapy:

• If HbA1c ≥10% (86 mmol/mol) or blood glucose ≥300 mg/dL (16.7 mmol/L), especially with symptoms of hyperglycemia (polyuria, polydipsia), weight loss, or ketosis, initiate insulin therapy immediately 1, 2
• Early combination therapy (dual therapy at diagnosis) can be considered if HbA1c ≥9% to extend time to treatment failure 1

Insulin Therapy

• When insulin is required, combination therapy with a GLP-1 receptor agonist is recommended for greater efficacy, durability, and to mitigate weight gain 1
• For significant prandial hyperglycemia, add rapid-acting insulin analogs (lispro, aspart, glulisine) before meals, targeting postprandial glucose <10.0 mmol/L 5
• Monitor for overbasalization: basal insulin dose >0.5 IU/kg/day, high bedtime-morning glucose differential, hypoglycemia, or high glycemic variability should prompt reevaluation 1

Obesity Management

• Diet, physical activity, and behavioral therapy designed to achieve ≥5% weight loss should be prescribed for patients who are overweight or obese 1
• Interventions should be high-intensity (≥16 sessions in 6 months) focusing on a 500-750 kcal/day energy deficit 1
• Weight loss of ≥5% produces clinically meaningful reductions in blood glucose, HbA1c, triglycerides, blood pressure, and medication requirements 1
• Physical activity alone can reduce HbA1c by 0.4-1.0% and improve cardiovascular risk factors 1, 4

Lipid Management

• Statin therapy should be added to lifestyle therapy regardless of baseline lipid levels for patients with diabetes and established cardiovascular disease or age >40 years with additional cardiovascular risk factors 1
• LDL cholesterol target <100 mg/dL (<2.6 mmol/L) for patients without atherosclerotic cardiovascular disease; <70 mg/dL (<1.8 mmol/L) for those with established disease 1
• Triglycerides <150 mg/dL (<1.7 mmol/L)** and **HDL cholesterol >40 mg/dL (>1.1 mmol/L) in men, >50 mg/dL (>1.3 mmol/L) in women 1

Screening for Complications

Nephropathy:

• Perform annual urine albumin quantification in type 2 diabetes starting at diagnosis 1
• Use ACE inhibitors or ARBs (not both) for urinary albumin excretion ≥30 mg/24 hours 1
• Monitor serum creatinine and potassium when using ACE inhibitors, ARBs, or diuretics 1
• Evaluate and manage complications of chronic kidney disease when eGFR <60 mL/min/1.73 m² 1

Retinopathy:

• Initial dilated comprehensive eye examination by ophthalmologist or optometrist shortly after type 2 diabetes diagnosis 1
• If no retinopathy for one or more exams, repeat every 2 years; if retinopathy present, repeat annually 1

Cardiovascular disease:

• Consider aspirin therapy 75-162 mg/day for primary prevention in patients at increased cardiovascular risk (10-year risk >10%) 1

Medication Regimen Review

• Reevaluate medication regimen and medication-taking behavior every 3-6 months and adjust as needed 1
• Assess adherence, side effects, hypoglycemia episodes, weight changes, and patient preferences at each visit 1

Common Pitfalls to Avoid

• Clinical inertia: Failure to initiate or intensify therapy when targets are not met is the most common error—do not delay treatment intensification beyond 3 months 1, 2, 6
• Discontinuing metformin: Keep metformin in the regimen when adding other agents unless contraindicated or not tolerated 1, 2
• Ignoring comorbidities: Failing to prioritize SGLT2 inhibitors or GLP-1 receptor agonists in patients with cardiovascular or kidney disease misses proven mortality and morbidity benefits 1, 4
• Focusing only on fasting glucose: Neglecting postprandial glucose control limits HbA1c improvement 5
• Inadequate patient education: Not teaching glucose monitoring, medication administration, hypoglycemia recognition, and lifestyle modifications undermines treatment success 5