What is the first line treatment for a patient with a family history of Type 2 Diabetes Mellitus, HbA1c of 8%, Fasting Blood Glucose of 9 mmol/L, and a BMI of 34: liraglutide or metformin?

First-Line Treatment: Metformin

Metformin is the first-line treatment for this patient with newly diagnosed type 2 diabetes (HbA1c 8%, fasting glucose 9 mmol/L, BMI 34). 1

Rationale for Metformin as Initial Therapy

Metformin should be initiated at or soon after diagnosis in all newly diagnosed patients with type 2 diabetes, unless contraindicated or not tolerated. 1 The American Diabetes Association explicitly states that metformin is the preferred initial pharmacologic agent based on its established efficacy, safety profile, cardiovascular benefits, and low cost. 1

Key Supporting Evidence

• Metformin has beneficial effects on HbA1c (expected reduction of approximately 1.5%), weight (weight neutral or modest weight loss), and cardiovascular mortality compared to sulfonylureas. 1
• The UKPDS demonstrated a 36% relative risk reduction in all-cause mortality and 39% reduction in myocardial infarction with metformin therapy. 2
• For this patient with BMI 34, metformin's weight-neutral profile or potential for modest weight loss is particularly advantageous. 3, 4

Practical Implementation

Starting Dose and Titration

• Begin with metformin 500 mg once or twice daily with meals to minimize gastrointestinal side effects. 1, 5
• Titrate by 500 mg weekly until reaching the effective dose of 1000 mg twice daily (2000 mg total daily dose). 5, 6
• Extended-release formulation can be considered if gastrointestinal side effects occur, taken once daily with the evening meal. 5, 6

Monitoring Requirements

• Check eGFR at baseline and at least annually, as metformin dosing depends on renal function. 5, 6
• Monitor vitamin B12 levels periodically, especially after 4 years of therapy or if neuropathy symptoms develop. 1, 5, 6

Why Not Liraglutide First-Line?

While GLP-1 receptor agonists like liraglutide have demonstrated cardiovascular benefits and are highly effective, they are not recommended as initial monotherapy in newly diagnosed patients without established cardiovascular disease, heart failure, or chronic kidney disease. 1

When to Consider Adding Liraglutide

• If HbA1c remains ≥1.5% above target after 3 months on maximum tolerated metformin dose, add a GLP-1 receptor agonist or SGLT2 inhibitor. 1
• For patients with established atherosclerotic cardiovascular disease, heart failure, or chronic kidney disease, GLP-1 receptor agonists or SGLT2 inhibitors should be added to metformin independent of HbA1c level. 1, 5
• This patient has no documented cardiovascular disease or chronic kidney disease, making metformin monotherapy the appropriate initial choice. 1

Common Pitfalls to Avoid

• Do not delay metformin initiation—it should be started at or soon after diagnosis alongside lifestyle modifications. 1
• Do not underdose metformin due to fear of side effects; gradual titration to 2000 mg daily is usually well-tolerated and necessary for optimal efficacy. 5, 6
• Do not avoid metformin in patients with mild-to-moderate renal impairment (eGFR 30-60 mL/min/1.73 m²); dose reduction is appropriate, but the drug can be safely continued. 1, 5
• Do not forget to reassess therapy at 3 months—if HbA1c target is not achieved, promptly add a second agent rather than continuing ineffective monotherapy. 1

Cost and Accessibility Considerations

Metformin is inexpensive and widely available, making it accessible for most patients, whereas liraglutide has significantly higher costs and potential insurance barriers. 1, 7 This practical consideration supports metformin as the appropriate first-line choice for this newly diagnosed patient without compelling indications for alternative initial therapy.