What is the recommended treatment for a patient with pre-diabetes, indicated by an elevated Hemoglobin A1c (HbA1c) level?

Treatment of Pre-Diabetes (A1C 5.7-6.4%)

Intensive lifestyle modification targeting 7% weight loss and 150 minutes per week of moderate-intensity physical activity is the first-line treatment for all patients with pre-diabetes, with metformin reserved as add-on therapy for high-risk individuals (younger than 60 years, BMI ≥35, fasting glucose ≥110 mg/dL, or A1C ≥6.0%). 1, 2, 3

Lifestyle Modification: The Foundation

All patients with pre-diabetes should begin intensive lifestyle intervention immediately, as this reduces diabetes incidence by 6.2 cases per 100 person-years over 3 years—nearly double the benefit of metformin alone. 3

Physical Activity Requirements

• Prescribe at least 150 minutes per week of moderate-intensity aerobic activity (such as brisk walking), spread over at least 3 days with no more than 2 consecutive days without exercise. 1, 2
• Add resistance training at least twice weekly for additional insulin sensitivity benefits. 2
• Emphasize breaking up prolonged sitting throughout the day, as this independently lowers postprandial glucose. 2

Weight Loss Goals

• Target 7-10% weight loss within the first 6 months through calorie restriction of 500-1,000 calories per day below maintenance needs. 1, 2
• The Diabetes Prevention Program demonstrated that achieving this 7% weight loss goal reduces diabetes risk by 58% over 3 years, with sustained benefits of 27% risk reduction even at 15 years. 1

Dietary Approach

• Multiple eating patterns are effective—Mediterranean-style, intermittent fasting, low-carbohydrate, or DASH diets can all work. 2
• Emphasize whole grains, legumes, nuts, fruits, and vegetables while minimizing refined/processed foods. 2
• No single macronutrient distribution is superior; individualize based on patient preference and current eating patterns. 2

Program Delivery

• Enroll patients in a CDC-recognized National Diabetes Prevention Program for structured, evidence-based lifestyle modification. 1, 2
• Group-based delivery in community or primary care settings is cost-effective while maintaining efficacy. 2
• Technology-assisted programs (online or app-based) are acceptable alternatives based on patient preference. 2

Pharmacologic Therapy: Add-On Treatment for High-Risk Patients

Metformin is most effective and should be added to lifestyle modification for patients younger than 60 years with BMI ≥35, fasting plasma glucose ≥110 mg/dL, or A1C ≥6.0%, reducing diabetes incidence by 3.2 cases per 100 person-years. 3

Specific High-Risk Groups for Metformin

• Women with prior gestational diabetes (highest benefit group). 3
• Patients with family history of type 2 diabetes and high BMI with year-to-year A1C increases. 4
• Younger patients (under 60 years) with obesity. 3

Newer Agents for Select Patients

• For patients with pre-diabetes who also have obesity and established cardiovascular disease, consider GLP-1 receptor agonist-based therapy as add-on to lifestyle modification. 2
• GLP-1 receptor agonists achieve 15-25% weight reduction and demonstrate cardiovascular event reduction in patients with obesity and CVD. 2
• SGLT2 inhibitors provide cardiovascular and renal protective effects and may be considered in high-risk individuals. 2

Monitoring Strategy

• Monitor A1C approximately every 6 months to assess disease progression and guide treatment adjustments. 2
• At least annual monitoring for development of type 2 diabetes is required in all patients with pre-diabetes. 1

Cardiovascular Risk Factor Management

Address hypertension, dyslipidemia, and smoking cessation aggressively, as pre-diabetes is associated with excess absolute risk of 7.36 per 10,000 person-years for mortality and 8.75 per 10,000 person-years for cardiovascular disease. 2, 3

Common Pitfalls to Avoid

• Do not rely solely on A1C for diagnosis without confirming with fasting glucose or oral glucose tolerance test, as A1C may be problematic in certain hemoglobinopathies or conditions affecting red blood cell turnover. 1
• Do not delay lifestyle intervention while waiting to start metformin—lifestyle modification should begin immediately for all patients. 1, 3
• Do not use adult A1C cutoffs for adolescents, as this significantly underestimates pre-diabetes prevalence in pediatric populations. 5
• Recognize that patients with A1C 5.7-6.4% who are older and have higher BMI may have elevated A1C due to age and adiposity rather than true glucoregulatory dysfunction—match for these factors when assessing risk. 6