Is metformin appropriate for a 45‑year‑old overweight (BMI 32 kg/m²) adult with prediabetes (fasting plasma glucose 110 mg/dL, 2‑hour oral glucose tolerance test 150 mg/dL, HbA1c 6.0 %) and estimated glomerular filtration rate ≥45 mL/min/1.73 m²?

Metformin for Prediabetes

Yes, metformin is appropriate for this 45-year-old overweight patient with prediabetes, particularly given the BMI of 32 kg/m², HbA1c of 6.0%, and adequate renal function (eGFR ≥45 mL/min/1.73 m²).

Evidence-Based Rationale

Lifestyle Intervention Remains First-Line

• The European Society of Cardiology and European Association for the Study of Diabetes recommend that people at high risk for type 2 diabetes should receive appropriate lifestyle counseling first, with pharmacological therapy added if needed to reduce or delay diabetes risk 1
• Lifestyle modification (targeting 7% weight reduction and 150 minutes/week of moderate physical activity) reduced diabetes incidence by 58% in the Diabetes Prevention Program, compared to 31% with metformin 1

When Metformin Should Be Added to Lifestyle Intervention

Metformin is specifically indicated when:

• BMI ≥32 kg/m² (this patient qualifies) 1
• Age <60 years (this patient is 45 years old) 1
• HbA1c ≥6.0% (this patient has HbA1c of 6.0%) 2
• Fasting plasma glucose 110-125 mg/dL (this patient has FPG of 110 mg/dL) 2

This patient meets all four high-risk criteria that predict greatest benefit from metformin therapy.

Efficacy Data

• Metformin reduces conversion from prediabetes to diabetes with a number needed to treat of 7-14 over 3 years 3
• The drug showed greater beneficial effect in people with higher baseline BMI and higher fasting plasma glucose 4
• In the Diabetes Prevention Program, metformin reduced diabetes incidence to 7.8 cases per 100 person-years versus 11.0 in the control group 1
• One case of diabetes is prevented for every 14 people with prediabetes treated with metformin for 3 years 1

Safety Considerations with This Patient's Renal Function

The patient's eGFR ≥45 mL/min/1.73 m² makes metformin safe:

• Metformin may be used safely in patients with eGFR ≥30 mL/min/1.73 m² 1
• Standard dosing is appropriate when eGFR ≥45 mL/min/1.73 m² 5
• The FDA states metformin is contraindicated only when eGFR <30 mL/min/1.73 m² 6
• Initiation is not recommended when eGFR is 30-45 mL/min/1.73 m², but this patient's renal function exceeds this threshold 6

Practical Implementation

Starting regimen:

• Begin with metformin 500 mg once daily with the largest meal 7
• Titrate by 500 mg weekly as tolerated to target dose of 850 mg twice daily or 1000 mg twice daily 1, 3
• Use extended-release formulation if gastrointestinal side effects occur 1, 7

Monitoring requirements:

• Check eGFR at least annually 6
• Monitor vitamin B12 levels periodically, especially if neuropathy symptoms develop 1, 7
• Temporarily discontinue during acute illness, hospitalization, or procedures with iodinated contrast 6

Addressing the Counterargument

One perspective argues against treating prediabetes with metformin, noting that two-thirds of people with prediabetes never develop diabetes and one-third return to normal glucose regulation 2. However, this argument fails to account for:

• This specific patient's high-risk profile (BMI 32, age 45, HbA1c 6.0%, FPG 110 mg/dL) places them in the subset most likely to progress to diabetes 2
• Cardiovascular and cancer-protective benefits of metformin extend beyond diabetes prevention 4
• The National Institute for Clinical Excellence (UK) specifically recommends metformin for adults at high risk who fail to adhere to lifestyle changes 4

Common Pitfalls to Avoid

• Do not use metformin as monotherapy without concurrent lifestyle intervention—both should be implemented together 1
• Do not prescribe glyburide or chlorpropamide if diabetes eventually develops, as these carry high hypoglycemia risk 1
• Do not continue metformin if eGFR falls below 30 mL/min/1.73 m² 6
• Do not ignore gastrointestinal side effects—switch to extended-release formulation or reduce dose temporarily 1, 7

Long-Term Strategy

If diabetes develops despite metformin:

• Continue metformin as first-line agent unless contraindicated 1
• Add SGLT2 inhibitor or GLP-1 receptor agonist if cardiovascular disease or chronic kidney disease develops 1
• Avoid sulfonylureas due to hypoglycemia risk 1

The combination of intensive lifestyle modification plus metformin 850 mg twice daily provides this patient the best evidence-based strategy to prevent or delay type 2 diabetes while maintaining an excellent safety profile given their preserved renal function.