What is the recommended treatment approach for diabetes mellitus, including lifestyle modification and pharmacologic therapy for type 1 and type 2 disease?

Treatment of Diabetes Mellitus

For type 2 diabetes, initiate metformin immediately at diagnosis alongside comprehensive lifestyle modifications, and add a GLP-1 receptor agonist or SGLT2 inhibitor if the patient has established cardiovascular disease, heart failure, or chronic kidney disease. 1, 2

Type 2 Diabetes Management

Initial Pharmacologic Therapy

Metformin is the cornerstone first-line medication for all adults with type 2 diabetes unless contraindicated (renal function must be >30 mL/min/1.73 m²). 3, 1, 2

• Start metformin at 500 mg daily and increase by 500 mg every 1-2 weeks to a target dose of 2000 mg daily in divided doses to minimize gastrointestinal side effects. 2
• Metformin reduces cardiovascular events and death, carries minimal hypoglycemia risk when used alone, and is inexpensive with long-established safety data. 1, 2
• For patients presenting with marked hyperglycemia (blood glucose ≥250 mg/dL or A1C ≥8.5%) with symptoms (polyuria, polydipsia, weight loss), initiate basal insulin immediately while simultaneously starting and titrating metformin. 3, 1

For patients with established atherosclerotic cardiovascular disease or high cardiovascular risk, add a GLP-1 receptor agonist to metformin immediately at diagnosis. 2

• GLP-1 receptor agonists reduce stroke risk by 12-26% and atherosclerotic cardiovascular disease events. 2

For patients with heart failure or chronic kidney disease, add an SGLT2 inhibitor to metformin immediately at diagnosis. 2

• SGLT2 inhibitors reduce heart failure hospitalizations by 18-25% and kidney disease progression by 24-39%. 2

Glycemic Targets

Target A1C <7% for most non-pregnant adults with type 2 diabetes. 3, 1

• More stringent A1C goals (<6.5%) are appropriate for patients with short diabetes duration, long life expectancy, and no significant cardiovascular disease if achievable without significant hypoglycemia. 3, 1
• Less stringent A1C goals (<8%) are appropriate for patients with history of severe hypoglycemia, limited life expectancy, advanced microvascular or macrovascular complications, extensive comorbidities, or longstanding diabetes difficult to control. 3

Treatment Intensification

If metformin monotherapy at maximum tolerated dose does not achieve A1C target over 3-6 months, add a second agent (oral agent, GLP-1 receptor agonist, or insulin). 3, 1

• Reevaluate medication regimen every 3-6 months and adjust based on A1C, weight goals, and comorbidities. 2
• When adding SGLT2 inhibitors or GLP-1 receptor agonists, reduce or discontinue sulfonylureas or long-acting insulin to avoid hypoglycemia. 2

Monitoring Schedule

Test A1C every 3 months until target is achieved, then at least twice yearly if stable and meeting treatment goals. 3, 1, 2

• Monitor vitamin B12 levels periodically in patients on metformin, as deficiency can worsen neuropathy symptoms. 2
• Monitor serum creatinine and potassium levels when using ACE inhibitors, ARBs, or mineralocorticoid receptor antagonists at routine visits and 7-14 days after initiation or dose change. 3

Lifestyle Modifications (Essential for Both Type 1 and Type 2)

Physical Activity

Prescribe at least 150 minutes per week of moderate-intensity aerobic activity (50-70% of maximum heart rate), spread over at least 5 days, preferably 7 days per week. 3, 1, 2

• Add resistance training at least 2 days per week on non-consecutive days for complementary benefits. 1, 2
• Reduce sedentary time throughout the day with activity breaks every 30 minutes. 2

Dietary Management

Implement a structured dietary pattern focusing on Mediterranean, DASH, or plant-based diets. 2

• Eliminate all sugar-sweetened beverages completely. 2
• Emphasize fiber-rich foods: 8-10 servings per day of vegetables and fruits, whole grains, legumes, low-fat dairy products (2-3 servings per day), and fresh fish. 3, 2
• Restrict sodium intake to <2,300 mg/day. 3
• Reduce red meat consumption and avoid refined carbohydrates and high-energy foods rich in saturated fats. 2
• Limit alcohol to ≤1 drink daily for women, ≤2 drinks daily for men; consume with food to prevent nocturnal hypoglycemia if on insulin or sulfonylureas. 3, 2

Weight Management

Target 5-10% weight reduction from baseline for overweight or obese patients to improve glycemic control and cardiovascular risk factors. 3, 1, 2

• Weight loss interventions should be high-intensity (≥16 sessions in 6 months) and focus on dietary changes, physical activity, and behavioral strategies to achieve a caloric deficit of 500-750 calories daily. 2

Type 1 Diabetes Management

Type 1 diabetes requires insulin therapy from diagnosis, as it is primarily an autoimmune disease with absolute insulin deficiency. 4

• For children and adolescents with type 1 diabetes, the challenge is maintaining good glycemic control while providing adequate energy for growth and development. 4
• Carbohydrates should be spread evenly throughout the day and matched to insulin dosing. 4
• The same A1C targets apply as for type 2 diabetes (<7% for most patients), with individualization based on hypoglycemia risk and life expectancy. 3

Cardiovascular Risk Management

For patients with diabetes and established coronary artery disease, ACE inhibitors or ARBs are recommended first-line therapy for hypertension. 3

Blood Pressure Management

For blood pressure >120/80 mmHg, initiate lifestyle interventions including weight loss when indicated, DASH-style eating pattern, sodium restriction, alcohol moderation, smoking cessation, and increased physical activity. 3

• For confirmed office-based blood pressure ≥140/90 mmHg, initiate pharmacologic therapy promptly in addition to lifestyle therapy. 3
• For blood pressure ≥150/90 mmHg, initiate two antihypertensive medications to more effectively achieve blood pressure goals. 3
• Initial treatment should include ACE inhibitors, ARBs, thiazide-like diuretics, or dihydropyridine calcium channel blockers—all demonstrated to reduce cardiovascular events in people with diabetes. 3
• For patients with albuminuria (UACR ≥30 mg/g), initiate an ACE inhibitor or ARB to reduce progressive kidney disease risk. 3

Important Caveats

• ACE inhibitors, ARBs, mineralocorticoid receptor antagonists, direct renin inhibitors, and neprilysin inhibitors are contraindicated in pregnancy and should be avoided in sexually active individuals of childbearing potential not using reliable contraception. 3
• Do not combine ACE inhibitors with ARBs or with direct renin inhibitors. 3

Pediatric Type 2 Diabetes

For youth with type 2 diabetes who are metabolically stable (A1C <8.5% and asymptomatic), metformin is the initial pharmacologic treatment of choice if renal function is >30 mL/min/1.73 m². 3

• Youth with marked hyperglycemia (blood glucose ≥250 mg/dL, A1C ≥8.5%) without ketoacidosis who are symptomatic should be treated initially with basal insulin while metformin is initiated and titrated. 3
• Overweight or obese youth with type 2 diabetes should receive developmentally and culturally appropriate comprehensive lifestyle programs integrated with diabetes management to achieve 7-10% decrease in excess weight. 3