What are the recommendations for the management of type 2 diabetes mellitus, including lifestyle modifications, oral medications, and monitoring?

Comprehensive Management of Type 2 Diabetes Mellitus

Metformin plus an SGLT-2 inhibitor or GLP-1 receptor agonist is the optimal treatment approach for most adults with type 2 diabetes, with medication selection based on comorbidities and specific patient factors. 1, 2

Glycemic Goals and Monitoring

Target Goals

• A1C target: 7-8% for most adults with type 2 diabetes 1, 2
• Preprandial glucose: 80-130 mg/dL
• Postprandial glucose: <180 mg/dL 2
• Consider deintensifying treatment if A1C <6.5% 1
• Individualize targets based on:
  • Hypoglycemia risk
  • Life expectancy
  • Disease duration
  • Comorbidities
  • Patient preferences 1, 2

Monitoring

• Check A1C quarterly when therapy changes or targets not met
• Check A1C twice yearly when stable and at goal 2
• Self-monitoring of blood glucose may be unnecessary for patients on metformin combined with SGLT-2 inhibitor or GLP-1 agonist 1
• Reevaluate medication regimen every 3-6 months 1, 2

Pharmacologic Management Algorithm

First-Line Therapy

• Metformin plus lifestyle modifications for most patients 1, 2
• Start at 500mg once or twice daily with meals
• Titrate gradually to effective dose of 1500-2000mg daily in divided doses 2
• Monitor for GI side effects and vitamin B12 deficiency 2
• Can continue with declining renal function down to GFR of 30-45 mL/min with dose reduction 2

Second-Line Therapy (when A1C targets not met after 3 months)

• Add SGLT-2 inhibitor for patients with:

  • Established cardiovascular disease
  • Heart failure
  • Chronic kidney disease (eGFR 20-60 mL/min/1.73m²)
  • To reduce all-cause mortality, MACE, CKD progression, and CHF hospitalization 1, 2

• Add GLP-1 receptor agonist for patients with:

  • Established cardiovascular disease
  • High stroke risk
  • Obesity/weight loss goals
  • To reduce all-cause mortality, MACE, and stroke 1, 2

Special Circumstances

• Early insulin consideration for:

  • A1C >10%
  • Blood glucose ≥300 mg/dL
  • Symptoms of hyperglycemia
  • Evidence of ongoing catabolism (weight loss) 1, 2

• For advanced CKD (eGFR <30 mL/min/1.73m²):

  • GLP-1 receptor agonist is preferred 2

Medication Adjustments

• When adding SGLT-2 inhibitor or GLP-1 agonist with adequate glycemic control:
  • Reduce or discontinue sulfonylureas or long-acting insulins to reduce hypoglycemia risk 1
• Avoid adding DPP-4 inhibitors to metformin (strong recommendation against) 1

Management of Hypoglycemia

• Define hypoglycemia as blood glucose <70 mg/dL 2
• Treat conscious individuals with 15-20g of glucose or carbohydrates 2
• Prescribe glucagon for all individuals at increased risk of severe hypoglycemia 2
• Educate caregivers and family members on glucagon administration 2

Required Screenings and Monitoring

• Annual comprehensive foot examination
• Annual dilated eye examination
• Annual nephropathy screening with urine albumin-to-creatinine ratio
• Blood pressure check at every routine visit
• Periodic screening for diabetes distress and depression 2

Lifestyle Modifications

• Physical Activity:

  • At least 150 minutes of moderate-intensity aerobic activity weekly
  • Spread over at least 3 days with no more than 2 consecutive days without activity
  • Resistance training 2-3 sessions/week on non-consecutive days 2

• Dietary Recommendations:

  • Emphasize carbohydrates from fruits, vegetables, whole grains, legumes, and low-fat milk
  • Monitor carbohydrate intake through counting, exchanges, or experience-based estimation
  • For overweight/obese patients, aim for 5-10% weight reduction 2, 3

Common Pitfalls to Avoid

• Clinical inertia: Delaying treatment intensification when glycemic targets aren't met 2
• Overbasalization with insulin: Watch for basal insulin dose exceeding 0.5 units/kg/day 2
• Ignoring comorbidities: Failing to consider cardiovascular and renal disease when selecting medications 2
• Metformin side effects: Monitor for vitamin B12 deficiency with long-term use 2
• Hypoglycemia risk: Particularly important with insulin and sulfonylureas; may require dose adjustment with exercise or fasting 2

Drug Class Details

Metformin

• MOA: Reduces hepatic gluconeogenesis and improves glucose uptake 4
• Benefits: Weight neutral, low hypoglycemia risk, possible cardiovascular benefits 4
• ADRs: GI side effects, vitamin B12 deficiency 2, 4
• CI/Precautions: Severe renal impairment (eGFR <30 mL/min/1.73m²), acute or unstable heart failure 2

SGLT-2 Inhibitors

• MOA: Inhibit glucose reabsorption in proximal tubule, increasing urinary glucose excretion
• Benefits: Cardiovascular protection, heart failure benefit, renal protection, weight loss 1, 2
• ADRs: Genital mycotic infections, urinary tract infections, volume depletion, DKA risk
• CI/Precautions: Severe renal impairment (varies by agent), history of DKA, type 1 diabetes

GLP-1 Receptor Agonists

• MOA: Increase glucose-dependent insulin secretion, decrease glucagon secretion, slow gastric emptying
• Benefits: Cardiovascular protection, weight loss, low hypoglycemia risk 1, 2
• ADRs: GI side effects (nausea, vomiting, diarrhea), injection site reactions
• CI/Precautions: Personal/family history of medullary thyroid carcinoma, MEN2, pancreatitis

Sulfonylureas

• MOA: Stimulate insulin secretion from pancreatic β-cells
• Benefits: Effective glucose lowering, low cost
• ADRs: Hypoglycemia, weight gain
• CI/Precautions: Severe renal or hepatic impairment, elderly patients at risk for hypoglycemia
• Note: Inferior to SGLT-2 inhibitors and GLP-1 agonists for mortality and morbidity outcomes 1