What is the initial management and treatment for type 2 diabetes?

Initial Management of Type 2 Diabetes

Start metformin 500 mg daily with dinner immediately at diagnosis alongside lifestyle modifications (diet and physical activity counseling) for all metabolically stable patients with type 2 diabetes. 1

Treatment Algorithm Based on Presentation Severity

Metabolically Stable Patients (A1C <8.5%, Asymptomatic)

• Begin metformin monotherapy as the first-line pharmacologic agent if renal function is normal (eGFR >30 mL/min/1.73 m²). 2, 1
• Start at 500 mg PO daily with dinner, then increase by 500 mg every 1-2 weeks as tolerated to reach target dose of 2000 mg daily in divided doses. 1
• Metformin provides glycemic control with minimal hypoglycemia risk and potential weight benefits. 1

Marked Hyperglycemia Without Acidosis (Blood Glucose ≥250 mg/dL or A1C ≥8.5%)

• Initiate dual therapy immediately: long-acting insulin PLUS metformin. 2, 1
• Start insulin glargine at 0.5 units/kg subcutaneously once daily at bedtime while simultaneously initiating metformin 500 mg PO daily. 2, 1
• Titrate insulin every 2-3 days based on blood glucose monitoring values. 2
• This applies to symptomatic patients with polyuria, polydipsia, nocturia, and/or weight loss. 2

Ketosis or Diabetic Ketoacidosis (DKA)

• Begin intravenous insulin infusion per DKA protocol until acidosis resolves, then transition to subcutaneous insulin. 2, 1
• Once ketosis/acidosis is resolved, add metformin 500 mg PO daily while continuing subcutaneous insulin therapy. 2, 1
• For severe hyperglycemia (blood glucose ≥600 mg/dL), assess for hyperglycemic hyperosmolar nonketotic syndrome. 2

Concurrent Lifestyle Interventions (Mandatory for All Patients)

• Provide behavioral counseling for healthful nutrition and physical activity changes at diagnosis—this is not optional. 2
• Physical activity can reduce A1C by 0.4% to 1.0% and improve cardiovascular risk factors including hypertension and dyslipidemia. 3
• Even moderate weight loss combined with increased activity improves insulin sensitivity and glycemic control. 4
• No specific diet has proven superiority for health outcomes, but weight management remains an important treatment component. 3

Treatment Intensification When Metformin Monotherapy Fails

• If A1C goals are not met with metformin alone, add a GLP-1 receptor agonist (such as semaglutide 0.25 mg subcutaneously weekly, titrated to 0.5-1.0 mg weekly) or SGLT2 inhibitor. 2, 1
• For patients ≥10 years old, GLP-1 receptor agonist therapy is approved if there is no personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia type 2. 2
• High-potency GLP-1 receptor agonists result in weight loss exceeding 5% in most individuals, with some achieving >10% weight loss. 3

Special Populations Requiring Modified Approach

Patients with Cardiovascular Disease or Heart Failure

• Add cardioprotective agents early: metformin 500 mg PO daily PLUS empagliflozin 10 mg PO daily or a GLP-1 receptor agonist. 1
• SGLT2 inhibitors and GLP-1 receptor agonists reduce atherosclerotic cardiovascular disease risk by 12-26%, heart failure risk by 18-25%, and kidney disease risk by 24-39% over 2-5 years. 3

Patients with Chronic Kidney Disease

• Metformin is safe if eGFR >30 mL/min/1.73 m². 1
• Add empagliflozin 10 mg PO daily or canagliflozin 100 mg PO daily for renal protection. 1

Pediatric/Adolescent Patients

• Metformin 500 mg PO daily with dinner, titrated to maximum 2000 mg daily in divided doses, with emphasis on family-centered lifestyle modifications. 1
• A multidisciplinary diabetes team (physician, diabetes educator, dietitian, psychologist/social worker) is essential for youth-onset diabetes. 2

Glycemic Targets and Monitoring

• Target A1C <7% for most adults, with <6.5% for selected individuals if achievable without hypoglycemia. 1
• Check A1C every 3 months until target achieved, then every 6 months. 1
• Lower A1C targets in youth with type 2 diabetes (compared to type 1) are justified by lower hypoglycemia risk and higher complication risk. 2
• Individualize targets based on life expectancy, comorbidities, hypoglycemia risk, and patient preferences. 1

Critical Pitfalls to Avoid

• Do not delay insulin in patients with marked hyperglycemia or ketosis—waiting worsens metabolic derangement and increases complication risk. 2
• Do not discontinue metformin when adding insulin unless contraindicated—combination therapy is more effective than insulin alone. 2
• Do not assume diabetes type in the first weeks of treatment, especially in youth with obesity—substantial overlap exists in presentation, and pancreatic autoantibody testing may be needed. 2
• Do not use metformin if eGFR <30 mL/min/1.73 m² due to lactic acidosis risk. 1