What are the steps for managing type 2 diabetes mellitus (T2DM) and what medications are used?

Step-by-Step Management of Type 2 Diabetes Mellitus (T2DM)

For optimal management of T2DM, implement a structured approach starting with lifestyle modifications followed by pharmacological therapy with metformin as first-line treatment, adding other agents based on patient-specific factors and comorbidities.

Step 1: Lifestyle Modifications (Foundation of Treatment)

Nutrition

• Implement balanced meal plan with 50-65% carbohydrates, 20-30% fat, and 15-20% protein 1
• Prioritize carbohydrates from vegetables, fruits, legumes, whole grains, and dairy products 1
• Consume most carbohydrates earlier in the day 1
• Eat protein and vegetables first, followed by carbohydrates 30 minutes later 1
• Limit sodium to <2,300 mg/day 1
• For overweight/obese patients, aim for ≥5% weight loss 1

Physical Activity

• Engage in at least 150 minutes of moderate-intensity aerobic activity weekly 1, 2
• Spread activity over at least 3 days with no more than 2 consecutive days without activity 1
• Perform 2-3 sessions of resistance exercise per week on non-consecutive days 1
• Break up prolonged sitting every 30 minutes with brief activity 1
• Reduce overall sedentary time 1

Other Lifestyle Factors

• Smoking cessation is essential for all diabetic patients 2, 1
• If consuming alcohol, limit to one drink per day for women and two drinks per day for men 1
• Address sleep disorders that may affect glycemic control 1, 3
• Manage stress through appropriate interventions 3
• Encourage social connections and peer support 1, 3

Step 2: Pharmacological Therapy

First-Line Therapy

• Start metformin as first-line pharmacological therapy for most adults with T2DM 2, 1
• Begin with low dose (500 mg daily) and gradually increase by 500 mg every 1-2 weeks 2
• Target maximum dose of 2000 mg daily in divided doses 2
• Monitor for gastrointestinal side effects (abdominal pain, bloating, loose stools) which are often transient 2, 4
• Contraindicated in renal insufficiency (eGFR <45 mL/min/1.73m²), liver dysfunction, severe infection, hypoxia 2

Second-Line Therapy (If HbA1c Target Not Achieved After 3 Months)

Add one of the following based on patient characteristics:

1. For patients with cardiovascular disease or high CV risk:

   • GLP-1 receptor agonists (preferred over sulfonylureas due to CV benefits and weight reduction) 2, 1
   • SGLT-2 inhibitors (especially for patients with heart failure or CKD) 2, 1

2. For patients without CV disease:

   • DPP-4 inhibitors (weight neutral with low hypoglycemia risk) 2, 1
   • Sulfonylureas (effective but risk of hypoglycemia and weight gain) 2, 1
   • Thiazolidinediones (effective but may cause weight gain and fluid retention) 2, 1, 5
   • SGLT-2 inhibitors 2
   • GLP-1 receptor agonists 2

Third-Line Therapy (If HbA1c Target Not Achieved After Adding Second Agent)

• Add a third oral agent from a different class 2
• Consider basal insulin if HbA1c remains >9% 2

Insulin Therapy

Initiate insulin therapy when:

• Random blood glucose ≥250 mg/dL 2
• HbA1c >9% 2
• Patient is ketotic or in diabetic ketoacidosis 2
• Distinction between T1DM and T2DM is unclear 2
• Oral agents fail to achieve glycemic targets 2

Step 3: Monitoring and Follow-up

Regular Monitoring

• Check HbA1c every 3 months 2, 1
• Intensify treatment if glycemic targets not met 2, 1
• Monitor finger-stick blood glucose in patients:
  • Taking insulin or medications with hypoglycemia risk 2
  • Initiating or changing diabetes treatment 2
  • Not meeting treatment goals 2
  • With intercurrent illnesses 2
• Regularly assess renal function, especially with SGLT-2 inhibitors and metformin 1

Treatment Targets

• General HbA1c target: <7% for most patients 1
• Individualize targets based on comorbidities and risk of complications 1

Step 4: Management of Comorbidities

• Aggressively manage cardiovascular risk factors including hypertension and dyslipidemia 2, 1
• Screen for and manage diabetes complications (retinopathy, nephropathy, neuropathy)
• Address obesity with appropriate weight management strategies 1
• Consider bariatric surgery for patients with BMI >35 kg/m² who have not responded to conventional therapy 6

Special Considerations

Pediatric T2DM Management

• For children/adolescents with T2DM who are ketotic or in DKA: start insulin therapy 2
• For children/adolescents with random BG ≥250 mg/dL or HbA1c >9%: start insulin therapy 2
• For all other pediatric T2DM cases: start lifestyle modifications and metformin 2

Common Pitfalls to Avoid

• Delaying intensification of therapy when glycemic targets are not met
• Overlooking the importance of lifestyle modifications when starting pharmacotherapy
• Failing to adjust medication doses appropriately based on renal function
• Not considering cardiovascular and renal benefits when selecting second-line agents
• Inadequate monitoring of potential medication side effects
• Neglecting to provide diabetes self-management education and support

By following this structured approach to T2DM management, clinicians can effectively control hyperglycemia, reduce the risk of complications, and improve patients' quality of life.