What is the treatment guideline for Diabetes mellitus (Type 2 Diabetes)?

Treatment Guidelines for Type 2 Diabetes Mellitus

For most adults with type 2 diabetes, treatment should begin with metformin and lifestyle modifications, followed by adding an SGLT-2 inhibitor or GLP-1 receptor agonist based on comorbidities, with SGLT-2 inhibitors prioritized for patients with heart failure or chronic kidney disease, and GLP-1 agonists prioritized for patients with high stroke risk or when weight loss is an important goal. 1, 2

Initial Management Approach

First-Line Therapy

• Metformin: Start as first-line pharmacologic therapy in most patients with T2D and eGFR ≥30 mL/min/1.73m² unless contraindicated 1, 2
• Lifestyle modifications: Should be implemented concurrently with medication
  • Physical activity: At least 150 minutes per week of moderate-intensity aerobic activity 2
  • Weight management: Target ≥5% weight loss for overweight/obese patients 2
  • Nutrition: Individualized approach focusing on reduced caloric intake for overweight/obese patients 2

Glycemic Targets

• Aim for HbA1c between 7% and 8% in most adults 1
• Deintensify pharmacologic treatments in adults with HbA1c levels <6.5% 1
• Reevaluate medication plan every 3-6 months and adjust as needed 2

Second-Line Therapy Selection Algorithm

For patients with inadequate glycemic control on metformin:

1. If patient has heart failure or chronic kidney disease:

   • Add an SGLT-2 inhibitor (strong recommendation; high-certainty evidence) 1, 2
   • Benefits: Reduces heart failure hospitalizations, slows CKD progression, provides cardiovascular risk reduction 1, 2

2. If patient has increased risk for stroke or weight loss is an important goal:

   • Add a GLP-1 receptor agonist (strong recommendation; high-certainty evidence) 1, 2
   • Benefits: Reduces risk for all-cause mortality, major adverse cardiovascular events, and stroke; promotes weight loss 1, 3

3. Avoid adding DPP-4 inhibitors:

   • The American College of Physicians strongly recommends against adding DPP-4 inhibitors to metformin and lifestyle modifications (strong recommendation; high-certainty evidence) 1

Medication Management Considerations

SGLT-2 Inhibitors (e.g., Empagliflozin)

• Provides statistically significant reductions in HbA1c, fasting plasma glucose, and body weight 4
• Reduces systolic blood pressure by 2.6-4.8 mmHg 4
• Monitor for potential side effects: genital mycotic infections, urinary tract infections, volume depletion, and rare risk of diabetic ketoacidosis 2

GLP-1 Receptor Agonists

• Can achieve weight loss >5% in most individuals, sometimes exceeding 10% 3
• Particularly beneficial for patients needing greater glucose lowering and weight management 2
• Lower risk of hypoglycemia compared to insulin and sulfonylureas 2

Medication Adjustments

• When adding an SGLT-2 inhibitor or GLP-1 agonist that results in adequate glycemic control, reduce or discontinue existing treatment with sulfonylureas or long-acting insulins to reduce hypoglycemia risk 1
• Monitor for vitamin B12 deficiency in patients on metformin for more than 4 years 2

Special Considerations

Monitoring Requirements

• HbA1c: Every 3-6 months (quarterly if not meeting targets, twice yearly if stable) 2
• Regular monitoring of blood pressure, lipids, weight, and kidney function 2
• Self-monitoring of blood glucose might be unnecessary in patients receiving metformin combined with either an SGLT-2 inhibitor or a GLP-1 agonist 1

Cardiovascular Risk Management

• Target blood pressure <130/80 mmHg 2
• Consider statin therapy for most persons with diabetes aged 40 years or older 2
• Use ACE inhibitor or ARB (but not both) for hypertension management 2

Common Pitfalls and Caveats

1. Medication cost barriers: Currently no generic SGLT-2 inhibitors or GLP-1 agonists are available. Discuss medication costs when selecting treatments 1

2. Hypoglycemia risk: Particularly high with insulin and sulfonylureas; use insulin analogs when possible to reduce this risk 2

3. Overreliance on medications alone: Collaborative care plans should include integrated efforts with dietary improvement, weight management, sleep health, physical activity, and stress management 1

4. Failure to address social determinants: Health systems should assess social risk factors and connect patients with social and community services 1

5. Inadequate monitoring of comorbidities: Regular assessment of cardiovascular risk factors, kidney function, and other diabetes-related complications is essential 2