What is the first line of management for hyperglycaemia?

First-Line Management of Hyperglycemia

Metformin is the optimal first-line pharmacological therapy for hyperglycemia in type 2 diabetes, unless contraindicated, and should be initiated at or soon after diagnosis, especially when lifestyle interventions alone are unlikely to achieve glycemic targets. 1

Initial Approach to Hyperglycemia Management

Lifestyle Interventions as Foundation

• Diet, exercise, and education remain the foundation of any type 2 diabetes treatment program 1
• Patients should aim for at least 150 minutes per week of moderate-intensity aerobic activity, including resistance and flexibility training 1
• Dietary advice must be personalized, emphasizing foods high in fiber (vegetables, fruits, whole grains, legumes) and limiting high-energy foods rich in saturated fats 1
• Weight reduction of 5-10% contributes meaningfully to achieving improved glucose control 1, 2

Pharmacological Therapy Initiation

• For patients with HbA1c already near target (<7.5%), highly motivated patients may engage in lifestyle changes for 3-6 months before starting pharmacotherapy 1
• For patients with moderate hyperglycemia or in whom lifestyle changes are anticipated to be unsuccessful, metformin should be promptly started at diagnosis 1
• Start metformin at a low dose with gradual titration to minimize gastrointestinal side effects 1

Special Circumstances Requiring Different Approaches

Severe Hyperglycemia

• If a patient presents with significant hyperglycemic symptoms and/or dramatically elevated plasma glucose (>300-350 mg/dL) or HbA1c (≥10.0-12.0%), insulin therapy should be strongly considered from the outset 1, 3
• Insulin therapy is mandatory when catabolic features are exhibited or if ketonuria is demonstrated 1
• Once symptoms are relieved, it may be possible to taper insulin partially or entirely, transferring to non-insulin agents 1

Gestational Diabetes

• For gestational diabetes, insulin is the first-line agent recommended in the U.S. when lifestyle modifications are insufficient 1
• While metformin and glyburide have been studied, they cross the placenta and long-term safety data are not available 1

Metformin as First-Line Therapy

Benefits of Metformin

• Reduces HbA1c levels by 1.0% to 1.5% versus placebo 1
• Generally considered weight-neutral with chronic use 1
• Does not increase the risk of hypoglycemia when used as monotherapy 1
• May provide modest cardiovascular benefits, though clinical trial data are not robust 1, 4

Contraindications and Precautions

• Contraindicated in renal insufficiency (eGFR < 45 mL/min/1.73m²), liver dysfunction, severe infection, hypoxia, or in patients undergoing major surgery 1
• Dose should be reduced if eGFR is 45-59 mL/min/1.73m² 1
• Should be temporarily discontinued for patients undergoing angiography with iodinated contrast agents 1
• Long-term use may cause vitamin B12 deficiency 1

Treatment Intensification

When Monotherapy is Insufficient

• If HbA1c target is not achieved after ~3 months, consider adding a second agent 1
• Options include sulfonylureas, thiazolidinediones, DPP-4 inhibitors, GLP-1 receptor agonists, or basal insulin 1
• Choice should be based on patient and drug characteristics, with the goal of improving glycemic control while minimizing side effects 1

Insulin Initiation

• The American Diabetes Association recommends beginning with basal insulin (insulin glargine, detemir, or NPH) in combination with current non-insulin agents 3
• Starting dose typically 10 IU per day, then titrated weekly to target fasting glucose 3
• Consider discontinuing sulfonylureas when initiating insulin to reduce hypoglycemia risk 3
• Maintain GLP-1 receptor agonists as they can be effectively combined with insulin 3

Monitoring and Follow-up

• Monitor fasting blood glucose daily when initiating insulin and adjust dose accordingly 3
• Consider adding prandial insulin if fasting glucose targets are achieved but HbA1c remains elevated after 3 months 3
• Regular follow-up, ideally within 1-2 weeks of treatment changes, is necessary to assess response and adjust therapy 3

Common Pitfalls to Avoid

• Delaying pharmacotherapy in patients unlikely to achieve targets with lifestyle modifications alone 1
• Failing to recognize severe hyperglycemia requiring immediate insulin therapy 1, 5
• Not starting metformin at a low dose, leading to poor tolerance and adherence 1
• Overlooking the importance of comprehensive cardiovascular risk reduction alongside glycemic control 1, 4