What is the next step for managing hyperglycemia (high blood sugar) in patients not controlled on metformin (Glucophage)?

Management of Hyperglycemia Uncontrolled on Metformin

When metformin monotherapy fails to achieve glycemic targets, adding basal insulin (NPH, insulin glargine, or insulin detemir) is a highly effective next step, particularly for patients with marked hyperglycemia or symptoms. 1

Treatment Algorithm Based on Clinical Presentation

For Patients with Severe Hyperglycemia or Symptoms

• If blood glucose ≥250 mg/dL (13.9 mmol/L) or HbA1c ≥8.5% with symptoms (polyuria, polydipsia, nocturia, weight loss): Initiate basal insulin immediately while continuing metformin 1
• If blood glucose >300-350 mg/dL or HbA1c ≥10-12%: Strongly consider insulin therapy from the outset, as this reflects more severe insulin deficiency 1
• If catabolic features present (weight loss, hypertriglyceridemia) or ketonuria: Insulin therapy is mandatory 1

For Patients with Moderate Hyperglycemia (Asymptomatic)

• If HbA1c <8.5% and asymptomatic: Combination therapy with an additional oral agent, GLP-1 receptor agonist, or basal insulin is reasonable 1
• After metformin failure: Add one agent from a different class; each new class typically lowers HbA1c by approximately 0.9-1.1% 1

Basal Insulin Selection and Dosing

Choice of Basal Insulin

Long-acting insulin analogs (glargine or detemir) offer modest advantages over NPH insulin 1:

• Less overnight hypoglycemia with both glargine and detemir compared to NPH 1
• Possibly slightly less weight gain with detemir 1
• Higher cost than NPH insulin 1
• Dosing differences: Detemir typically requires higher average unit requirements than glargine 1

Insulin Initiation Strategy

• Start with basal insulin alone unless patient is markedly hyperglycemic and symptomatic 1
• Goal: Suppress hepatic glucose production between meals and during sleep 1
• Target fasting plasma glucose: 4.0-5.5 mmol/L (72-99 mg/dL) 2
• Continue metformin when adding insulin, as combination therapy is more effective than either agent alone 3, 2

Evidence for Insulin Plus Metformin Combination

Combination therapy with basal insulin and metformin achieves superior glycemic control compared to either agent alone 3, 2:

• In patients with inadequate control on oral agents, adding basal insulin to metformin reduced HbA1c by approximately 1.7% 3
• Both insulin glargine plus metformin and NPH plus metformin can achieve good glycemic control (mean HbA1c ~7.1%) 2
• Insulin glargine with metformin showed fewer symptomatic hypoglycemic episodes (4.1 vs 9.0 episodes/patient-year) during initial 12 weeks compared to NPH with metformin 2

Progression to More Intensive Insulin Regimens

If basal insulin alone does not achieve targets, progression to prandial insulin is necessary 1:

• Add rapid-acting insulin analogs (lispro, aspart, or glulisine) before meals 1
• These provide better postprandial glucose control than regular human insulin 1
• Majority of type 2 diabetes patients can be successfully treated with basal insulin alone; prandial insulin is needed only when insulin secretory capacity progressively diminishes 1

Critical Patient Education Components

Proper education is imperative when initiating insulin 1:

• Glucose monitoring techniques and frequency 1
• Insulin injection technique and storage 1
• Recognition and treatment of hypoglycemia 1
• "Sick day" management rules 1
• Self-adjustment of insulin doses based on glucose trends 1, 2

Common Pitfalls to Avoid

• Do not use sliding scale insulin alone as primary therapy; basal-bolus regimens are superior for glycemic control 1
• Avoid metformin in patients with eGFR <30 mL/min/1.73 m², risk of lactic acidosis, or acute illness with hypoxia/shock 1, 3
• Monitor for hypoglycemia risk when combining insulin with metformin, though risk is lower than with sulfonylureas 3
• Do not delay insulin initiation in symptomatic patients or those with very high glucose levels, as early intervention prevents further metabolic decompensation 1