What is the treatment for an adult with prediabetes?

Treatment of Prediabetes

All adults with prediabetes should be referred to an intensive lifestyle behavior change program targeting at least 7% weight loss through reduced-calorie diet and 150 minutes per week of moderate-intensity physical activity, with metformin added for high-risk individuals (BMI ≥35 kg/m², age 25-59 years, fasting glucose ≥110 mg/dL, A1C ≥6.0%, or prior gestational diabetes). 1

Lifestyle Interventions: First-Line Treatment

Weight Loss Target

• Achieve 7-10% reduction in initial body weight through caloric restriction of 500-1,000 calories/day below maintenance levels 1
• Weight loss pace should be 1-2 pounds (0.5-1 kg) per week 1
• Even 5% weight loss improves insulin resistance and reduces diabetes risk 2
• This approach reduces diabetes incidence by 58% at 3 years, with sustained benefits of 27-43% risk reduction at 7-20 years follow-up 1, 3

Physical Activity Prescription

• Minimum 150 minutes per week of moderate-intensity aerobic activity (such as brisk walking), distributed over at least 3 days with no more than 2 consecutive days without exercise 1, 2
• Add resistance training 2-3 times per week as supplemental exercise 1
• Break up prolonged sedentary time throughout the day 1
• Exercise alone (without weight loss) reduces diabetes risk by 44% 4

Dietary Approach

• No single macronutrient distribution is ideal—individualize based on current eating patterns and preferences 1
• Emphasize whole grains, legumes, nuts, fruits, and vegetables while minimizing refined and processed foods 1, 4
• Acceptable eating patterns include Mediterranean-style, low-carbohydrate, vegetarian/plant-based, and DASH diets 1, 4
• Eliminate or minimize sugar-sweetened beverages, refined grains, and ultraprocessed foods 2
• Higher intake of nuts, berries, yogurt, coffee, and tea reduces diabetes risk; avoid red meats 3

Program Delivery

• Refer to CDC-recognized Diabetes Prevention Program (DPP) or equivalent intensive behavioral counseling program with frequent follow-up sessions 1, 3
• Refer to registered dietitian nutritionist (RDN) for individualized medical nutrition therapy at diagnosis and regular intervals—this effectively reduces A1C, weight, and waist circumference 1, 2
• Technology-assisted programs (smartphone apps, web-based, telehealth) are acceptable alternatives, particularly for rural or low-income populations, but must be CDC-certified 1
• Community health workers can effectively deliver DPP-like interventions and bridge social determinants of health barriers 1

Pharmacologic Interventions

Metformin: Primary Pharmacologic Option

Consider metformin for adults at high risk, specifically: 1

• Age 25-59 years with BMI ≥35 kg/m²
• Fasting plasma glucose ≥110 mg/dL (6 mmol/L)
• A1C ≥6.0% (42 mmol/mol)
• Women with prior gestational diabetes mellitus

Metformin reduces diabetes incidence by 31% relative risk reduction and was as effective as lifestyle modification in younger adults (age 25-44) and those with BMI ≥35 kg/m² in the DPP trial 1, 3, 2

Critical monitoring caveat: Long-term metformin use causes vitamin B12 deficiency, with higher risk after 4-5 years of treatment 1. Check vitamin B12 levels annually in patients on metformin >4 years or those with anemia, peripheral neuropathy, or vegan diet 1, 3

Alternative Pharmacologic Agents

No pharmacologic agent is FDA-approved specifically for diabetes prevention—all use is off-label 1

• GLP-1 receptor agonists: Most effective pharmacologic option with RR 0.28 (95% CrI 0.15-0.50), also provide cardiovascular benefits and 15-25% weight reduction 1, 5
• Pioglitazone: Consider only in patients with prior stroke, insulin resistance, and prediabetes to reduce recurrent stroke/MI risk—balance against weight gain, edema, and fracture risk; use lower doses to mitigate adverse effects 1
• Acarbose: RR 0.66 for diabetes prevention; start 25 mg three times daily with meals, titrate every 4-8 weeks to maximum 50-100 mg three times daily based on body weight 6, 5
• Orlistat and thiazolidinediones: Effective (RR 0.33 for both) but limited by side effects 5, 7

Vitamin D therapy: Despite Endocrine Society advocacy, evidence remains insufficient—three large RCTs showed non-significant modest benefits, optimal dosing unclear, and benefit-to-risk ratio uncertain 1

Avoid statins in prediabetes—they increase diabetes risk by 20% relative risk 5

Cardiovascular Risk Management

All patients with prediabetes have heightened cardiovascular risk 3

• Screen and treat hypertension, dyslipidemia, and tobacco use using same targets as general population 3
• Consider lipid-lowering therapy, blood pressure management, and potentially GLP-1 RA or SGLT2i for cardiovascular protection 1
• Lifestyle interventions reduce cardiovascular risk factors and medication requirements 3

Monitoring Strategy

• Check fasting glucose, 2-hour OGTT, or A1C at least annually to assess progression to diabetes 3, 2
• Monitor cardiovascular risk factors (blood pressure, lipid profile) regularly 4
• For patients on metformin >4 years: annual vitamin B12 assessment 1
• Use one-hour postprandial glucose during initial metformin titration, then A1C every 3 months 6

Implementation Algorithm

Step 1: Diagnose prediabetes and assess risk factors (BMI, age, fasting glucose, A1C, GDM history)

Step 2: Immediately refer to:

• CDC-recognized DPP or intensive lifestyle program 1
• Registered dietitian for medical nutrition therapy 1, 2

Step 3: Prescribe lifestyle intervention:

• 7-10% weight loss target 1
• 150 min/week moderate-intensity activity 1, 2
• Individualized healthy eating pattern 1, 4

Step 4: Add metformin if high-risk (BMI ≥35, age 25-59, FPG ≥110, A1C ≥6.0%, or prior GDM) 1

Step 5: If obesity present and <7% weight loss achieved with lifestyle alone, add GLP-1 RA-based therapy 1

Step 6: Screen and treat cardiovascular risk factors 3

Step 7: Monitor annually for diabetes progression and adjust therapy 3, 2

Common Pitfalls

• Failing to refer to structured programs: Individual counseling alone is less effective than intensive group-based DPP programs 1
• Delaying metformin in high-risk patients: Metformin should be started concurrently with lifestyle intervention in appropriate candidates, not after lifestyle "failure" 1, 3
• Ignoring vitamin B12 monitoring: This is a frequently overlooked but important complication of long-term metformin use 1, 3
• Prescribing statins without considering diabetes risk: Statins increase diabetes incidence by 20% in this population 5
• Setting vague lifestyle goals: Specific targets (7% weight loss, 150 min/week activity) are more effective than general advice 1