What is the treatment for a type 2 diabetes (T2D) patient?

Treatment of Type 2 Diabetes

Start all patients with metformin plus lifestyle modifications immediately at diagnosis, then add an SGLT-2 inhibitor or GLP-1 receptor agonist when glycemic control remains inadequate, as these newer agents reduce mortality and major cardiovascular events. 1

Initial Management: First-Line Therapy

• Initiate metformin at diagnosis along with lifestyle interventions unless contraindicated 2, 1, 3
• Start metformin at 500 mg daily, increase by 500 mg every 1-2 weeks up to maximum dose of 2000 mg daily in divided doses 2
• Gastrointestinal side effects (abdominal pain, bloating, loose stools) are often transient and resolve with continued use 2
• Monitor for vitamin B12 deficiency with long-term metformin use, especially in patients with anemia or peripheral neuropathy 1, 3, 4

Exception: When to Start Insulin Instead

Use insulin therapy from the outset (with or without additional agents) if the patient presents with: 2

• Blood glucose ≥250 mg/dL or HbA1c >9% 2
• Ketoacidosis or ketosis 2
• Markedly symptomatic hyperglycemia 2

Lifestyle Modifications (Mandatory for All Patients)

Dietary Interventions

• Consume a diet high in vegetables, fruits, whole grains, fiber, legumes, plant-based proteins, unsaturated fats, and nuts 2
• Restrict calorie intake to 1500 kcal/day 1
• Limit fat to 30-35% of total energy intake 1
• Reduce processed meats, refined carbohydrates, and sweetened beverages 2
• Protein intake should be 0.8 g/kg/day for patients with chronic kidney disease 2
• Sodium intake should be <2 g per day (or <90 mmol per day, or <5 g sodium chloride per day) 2

Physical Activity Requirements

• Perform at least 150 minutes per week of moderate-intensity aerobic physical activity (50-70% of maximum heart rate), spread over at least 3 days with no more than 2 consecutive days without exercise 2
• Target 30 minutes of physical activity at least five times weekly 1
• Physical activity can reduce HbA1c by 0.4% to 1.0% and improve cardiovascular risk factors 5
• Lifestyle interventions alone can decrease HbA1c by approximately 2% and produce weight loss of 5 kg 1

Second-Line Therapy: Adding SGLT-2 Inhibitors or GLP-1 Receptor Agonists

If metformin at maximal tolerated dose does not achieve HbA1c target over 3-6 months, add either an SGLT-2 inhibitor or GLP-1 receptor agonist. 2, 1, 3

When to Prioritize SGLT-2 Inhibitors

Strongly prioritize SGLT-2 inhibitors in patients with: 1, 3

• Congestive heart failure (18-25% risk reduction) 3, 5
• Chronic kidney disease with eGFR ≥30 mL/min per 1.73 m² (24-39% risk reduction in kidney disease progression) 2, 3, 5
• Need for cardiovascular mortality reduction 1, 3
• SGLT-2 inhibitors reduce all-cause mortality, major adverse cardiovascular events, and hospitalization due to heart failure 3, 5

When to Prioritize GLP-1 Receptor Agonists

Strongly prioritize GLP-1 receptor agonists in patients with: 1, 3

• Increased stroke risk (12-26% risk reduction in atherosclerotic cardiovascular disease) 1, 3, 5
• Need for weight loss (most individuals achieve >5% weight loss, may exceed 10% with high-potency agents) 1, 3, 5
• Need for all-cause mortality reduction 1, 3
• Use long-acting formulations for patients with CKD who have not achieved glycemic targets despite metformin and SGLT-2 inhibitors 2

Glycemic Targets

• Target HbA1c between 7% and 8% for most adults with type 2 diabetes 2, 1, 3
• Consider more stringent target (HbA1c <6.5%) for patients with short diabetes duration, long life expectancy, and no significant cardiovascular disease if achievable without hypoglycemia 2
• Use less stringent target (HbA1c <8%) for patients with history of severe hypoglycemia, limited life expectancy, advanced complications, or extensive comorbidities 2
• Deintensify treatment when HbA1c falls below 6.5% to avoid hypoglycemia and overtreatment 1, 3
• Individualize targets based on hypoglycemia risk, life expectancy, diabetes duration, established vascular complications, and major comorbidities 2, 1, 3

Critical Safety Consideration: Preventing Hypoglycemia

When SGLT-2 inhibitors or GLP-1 agonists achieve adequate glycemic control, reduce or discontinue sulfonylureas or long-acting insulins due to severe hypoglycemia risk 1, 3

Monitoring

• Perform HbA1c testing at least twice yearly in patients meeting treatment goals with stable glycemic control 2
• Perform HbA1c testing quarterly in patients whose therapy has changed or who are not meeting glycemic goals 2
• Self-monitoring of blood glucose is likely unnecessary in patients receiving metformin combined with either SGLT-2 inhibitor or GLP-1 agonist, as these combinations carry minimal hypoglycemia risk 1, 3

What NOT to Use

Do not add DPP-4 inhibitors to metformin because they do not reduce morbidity or all-cause mortality (strong recommendation, high-certainty evidence) 1, 3

Weight Management Considerations

For Overweight/Obese Patients (BMI ≥27 kg/m²)

• When choosing glucose-lowering medications, consider their effect on weight 2
• Minimize medications for comorbid conditions that are associated with weight gain 2
• Weight loss medications may be effective as adjuncts to diet, physical activity, and behavioral counseling 2
• Discontinue weight loss medication if response is <5% weight loss after 3 months or if safety/tolerability issues arise 2

Metabolic Surgery Indications

• Recommend metabolic surgery for appropriate surgical candidates with BMI ≥40 kg/m² (≥37.5 kg/m² in Asian Americans), regardless of glycemic control level 2
• Consider metabolic surgery for adults with BMI 35.0-39.9 kg/m² (27.5-32.4 kg/m² in Asian Americans) if hyperglycemia is inadequately controlled despite lifestyle and optimal medical therapy 2
• Consider metabolic surgery for adults with BMI 30.0-34.9 kg/m² (27.5-32.4 kg/m² in Asian Americans) if hyperglycemia is inadequately controlled despite optimal medical control 2
• Perform metabolic surgery in high-volume centers with multidisciplinary teams experienced in diabetes and gastrointestinal surgery 2

Additional Therapy Considerations

Role of Older Agents

• Sulfonylureas and long-acting insulins are inferior to SGLT-2 inhibitors and GLP-1 agonists for reducing mortality and morbidity but may still provide glycemic control value in cost-constrained situations 1, 3
• Approximately one-third of patients with type 2 diabetes require insulin treatment during their lifetime 5

Cost and Access

• No generic SGLT-2 inhibitors or GLP-1 agonists currently exist, so discuss medication costs with patients when selecting specific agents 1
• Prescribe generic medications when available rather than brand-name alternatives 1

Comprehensive Care Elements

• Provide diabetes self-management education at diagnosis and as needed thereafter 2
• Address psychosocial issues, as emotional well-being is associated with positive diabetes outcomes 2
• Involve clinical pharmacists in medication management to reduce polypharmacy risks 1
• Address sleep health, stress management, and all comorbidities as part of integrated care 1, 6
• Treat with angiotensin-converting enzyme inhibitor or angiotensin receptor blocker if patient has diabetes, hypertension, and albuminuria, titrated to highest approved tolerated dose 2
• Advise patients who use tobacco to quit using tobacco products 2