What are the treatment options for managing hyperglycaemia?

Management of Hyperglycaemia

Begin with lifestyle interventions (diet and exercise) combined with metformin as first-line pharmacotherapy unless contraindicated, then escalate systematically based on glycemic response, cardiovascular risk, and renal function. 1

Initial Assessment and Treatment Algorithm

Step 1: Assess Severity of Hyperglycemia

Severe hyperglycemia (glucose >300-350 mg/dL or HbA1c ≥10-12%) with symptoms:

• Initiate insulin therapy immediately, especially if catabolic features (weight loss, polyuria, polydipsia) or ketonuria are present 1, 2
• Insulin is mandatory when ketosis is demonstrated, reflecting profound insulin deficiency 1, 2
• Once symptoms resolve and glucose stabilizes, you can taper insulin and transition to oral agents if appropriate 1

Marked hyperglycemia (glucose ≥250 mg/dL or HbA1c ≥8.5-9%):

• Consider starting combination therapy with two agents or insulin plus metformin from the outset, as monotherapy has low probability of achieving target 1, 2
• For patients already on maximum-dose metformin with HbA1c ≥10%, add basal insulin (glargine, detemir, or NPH) starting at 10 units daily, titrated weekly to fasting glucose target of 72-99 mg/dL 2

Mild-moderate hyperglycemia (HbA1c 7-8.5%):

• Start with lifestyle modification plus metformin monotherapy 1

Step 2: Lifestyle Interventions (Foundation for All Patients)

Diet, exercise, and diabetes self-management education remain the foundation of any treatment program 1

• Medical nutrition therapy should emphasize reduced saturated fat intake, increased dietary fiber, and lower glycemic index foods 1, 3
• Physical activity recommendations should target at least 150 minutes per week of moderate-intensity exercise 1
• Weight loss interventions (lifestyle, medication, or bariatric surgery) are recommended for patients with obesity 1

Step 3: First-Line Pharmacotherapy

Metformin is the optimal first-line drug unless contraindicated or not tolerated 1

• Start at low dose (500 mg daily) with gradual titration to minimize gastrointestinal side effects 1, 4
• Maximum dose is 2000 mg daily in divided doses 4
• Initiate at or soon after diagnosis, especially when lifestyle intervention alone is unlikely to achieve HbA1c goals 1

Contraindications to metformin:

• eGFR <30 mL/min/1.73 m² (absolute contraindication) 4
• For eGFR 30-44 mL/min/1.73 m², reduce dose by half 4
• For eGFR 45-59 mL/min/1.73 m², consider dose reduction in certain conditions 4

Step 4: Second-Line Therapy (If HbA1c Target Not Achieved After 3 Months)

For patients with established cardiovascular disease:

• Add an SGLT2 inhibitor (empagliflozin) or GLP-1 receptor agonist with proven cardiovascular benefit 1
• This recommendation prioritizes mortality and morbidity reduction over glycemic control alone 1

For patients with chronic kidney disease or heart failure:

• Add an SGLT2 inhibitor with proven benefit in these conditions 1
• Empagliflozin reduces HbA1c by 0.5-0.7% when added to metformin, with additional benefits of weight loss (1.8-3.2 kg) and blood pressure reduction 5

For patients without cardiovascular disease or CKD:

• Add one of the following to metformin: sulfonylurea, TZD, DPP-4 inhibitor, GLP-1 receptor agonist, or basal insulin 1
• Choice depends on avoiding side effects: sulfonylureas cause hypoglycemia and weight gain; TZDs cause weight gain and fluid retention; GLP-1 agonists promote weight loss but may cause GI side effects 1

Step 5: Intensification to Insulin Therapy

Many patients will ultimately require insulin alone or in combination with other agents 1

When to add insulin:

• HbA1c remains above target despite optimal doses of 2-3 oral/injectable agents 1
• Progressive beta-cell failure over time makes insulin necessary 1

Insulin regimen selection:

• Start with basal insulin (glargine, detemir, NPH) at 10 units daily, maintaining current non-insulin agents 2
• Discontinue sulfonylureas when starting insulin to reduce hypoglycemia risk 2
• Continue metformin unless contraindicated (insulin plus metformin limits weight gain) 1, 2
• Continue GLP-1 receptor agonists as they combine effectively with insulin and limit weight gain 2
• Titrate basal insulin weekly targeting fasting glucose 72-99 mg/dL 2
• If fasting glucose controlled but HbA1c remains elevated after 3 months, add prandial (mealtime) insulin 2

For patients on multiple daily insulin injections:

• Adding empagliflozin 10-25 mg reduces HbA1c by an additional 0.9-1.0% and promotes weight loss of 1.95-2.04 kg 5

Critical Monitoring and Follow-Up

Reassess HbA1c every 3 months until target achieved, then every 6 months 1

• If target not achieved within 3 months, escalate therapy promptly 1
• Monitor renal function at least annually, or every 3-6 months in patients with reduced function 4
• Monitor for vitamin B12 deficiency in patients on metformin >4 years 4

Patient education is imperative:

• Glucose monitoring techniques, insulin injection technique, insulin storage 1, 2
• Recognition and treatment of hypoglycemia 1, 2
• "Sick day" rules for managing illness 1, 2
• Consider referral to certified diabetes educator 1, 2

Common Pitfalls to Avoid

Clinical inertia: The most common error is delaying treatment intensification when targets are not met 1. Escalate therapy within 3 months if HbA1c remains above goal 1.

Ignoring cardiovascular risk: In patients with established ASCVD, prioritizing agents with proven cardiovascular benefit (SGLT2 inhibitors, GLP-1 agonists) over glycemic efficacy alone reduces mortality 1.

Inappropriate insulin dosing: Starting insulin too conservatively or failing to titrate adequately leads to persistent hyperglycemia 2. Use structured titration protocols targeting fasting glucose 72-99 mg/dL 2.

Polypharmacy without insulin: Attempting to avoid insulin by adding multiple oral agents often results in poor control, increased side effects, and higher costs 1. When 2-3 agents fail, add insulin rather than a fourth oral agent 1.