What is the management of diabetes mellitus?

Management of Diabetes Mellitus

All patients with diabetes should begin with lifestyle modifications and metformin as first-line pharmacologic therapy, unless severe hyperglycemia or specific contraindications are present. 1, 2

Foundation: Lifestyle Modifications (Required for All Patients)

• Initiate comprehensive diabetes self-management education focusing on nutrition therapy and structured physical activity at diagnosis 2, 3
• Prescribe at least 150 minutes of moderate-intensity aerobic activity weekly plus resistance training twice per week 2, 3
• Target weight loss of at least 5-7% of starting weight in overweight/obese patients with type 2 diabetes 1, 2, 3
• Emphasize nutrient-dense, high-quality foods while decreasing calorie-dense, nutrient-poor foods 2

Type 1 Diabetes Management

Initiate multiple daily insulin injections (≥3 injections daily) or continuous subcutaneous insulin infusion at diagnosis 2, 3, 4, 5

Insulin Regimen for Type 1 Diabetes:

• Use basal insulin analogues (glargine, detemir, or degludec) over NPH insulin to reduce hypoglycemia risk 1, 4, 5
• Administer rapid-acting insulin analogues (lispro, aspart, or glulisine) 0-15 minutes before meals for prandial coverage 1, 4, 5
• Educate patients on matching prandial insulin doses to carbohydrate intake, preprandial blood glucose, and anticipated activity 2, 5
• Implement continuous glucose monitoring to significantly reduce severe hypoglycemia risk 2, 3, 5

Glycemic Targets for Type 1 Diabetes:

• Target HbA1c <7% (53 mmol/mol) for most nonpregnant adults; <7.5% (58 mmol/mol) for children 4, 5
• Monitor HbA1c every 3 months until target reached, then at least twice yearly 2

Type 2 Diabetes Management: Stepwise Algorithm

Step 1: Initial Pharmacologic Therapy

Start metformin at or soon after diagnosis alongside lifestyle modifications 1, 2, 3

• Begin metformin at low dose and titrate gradually to maximum tolerated dose of 2000 mg daily in divided doses 2
• Metformin is preferred due to efficacy, safety, low cost, and potential cardiovascular benefits 1, 2
• Continue metformin in declining renal function down to GFR 30-45 mL/min with dose reduction 1

Critical Exception: If patient has established atherosclerotic cardiovascular disease, heart failure, or chronic kidney disease, consider adding GLP-1 receptor agonist or SGLT2 inhibitor at diagnosis 3

Step 2: When to Bypass Metformin and Start Insulin Immediately

Initiate insulin therapy instead of metformin when: 2, 4

• Ketosis or diabetic ketoacidosis present
• Random blood glucose ≥250 mg/dL (13.9 mmol/L)
• HbA1c >8.5%
• Symptomatic diabetes with polyuria, polydipsia, and weight loss

For severe hyperglycemia (blood glucose 300-350 mg/dL or HbA1c 10-12%), especially with catabolic features, start basal insulin plus mealtime insulin immediately 1

Step 3: Intensification When Monotherapy Fails

Add a second agent when metformin at maximum tolerated dose fails to achieve HbA1c target after 3 months 1, 2

Second-line options to combine with metformin: 1

• Sulfonylureas
• Thiazolidinediones (pioglitazone)
• DPP-4 inhibitors
• SGLT2 inhibitors
• GLP-1 receptor agonists
• Basal insulin

For HbA1c ≥9%, start dual-regimen combination therapy immediately to achieve glycemic control more rapidly 1

Step 4: Insulin Initiation in Type 2 Diabetes

When to add insulin: 1, 4

• HbA1c ≥7.5% (58 mmol/mol) despite optimal oral agents
• HbA1c ≥10% (86 mmol/mol) when diet, physical activity, and other agents optimally used

Preferred insulin initiation method: 1, 4

• Start with basal insulin (NPH, glargine, detemir, or degludec) at 10 units or 0.1-0.2 units/kg body weight 1
• Continue metformin and possibly one additional noninsulin agent 1
• Titrate basal insulin based on fasting blood glucose levels 1

Step 5: Adding Prandial Insulin Coverage

When basal insulin is titrated to appropriate fasting glucose but HbA1c remains above target, add combination injectable therapy: 1

Options for postprandial glucose control:

• GLP-1 receptor agonist 1
• Rapid-acting insulin (lispro, aspart, or glulisine) administered immediately before meals 1
• Twice-daily premixed insulin analogues (70/30 aspart mix or 75/25 or 50/50 lispro mix), though suboptimal for postprandial coverage 1

When bolus insulin is needed, insulin analogues are preferred because they are faster-acting 1

Managing Oral Agents with Insulin

When initiating basal insulin only: 1

• Continue metformin
• Continue one additional noninsulin agent if used

When using more complicated insulin regimens (beyond basal insulin): 1

• Withdraw sulfonylureas, DPP-4 inhibitors, and GLP-1 receptor agonists 1
• May continue thiazolidinediones (pioglitazone) or SGLT2 inhibitors to improve glucose control and reduce total daily insulin dose 1

Critical Safety Considerations and Pitfalls

Hypoglycemia Management:

• Treat hypoglycemia (glucose <3.9 mmol/L or 70 mg/dL) with 15-20g rapid-acting glucose, recheck after 15 minutes, and repeat if needed 2
• Severe or frequent hypoglycemia is an absolute indication for treatment regimen modification 2, 3
• Patients with hypoglycemia unawareness must increase glycemic targets temporarily for several weeks to partially reverse this condition 2, 3

Insulin Dose Adjustments:

• When combining insulin with sulfonylureas, decrease sulfonylurea dose if hypoglycemia occurs 1
• When adding insulin to existing insulin therapy, decrease insulin dose by 10-25% if hypoglycemia occurs or plasma glucose <100 mg/dL 1
• Timely dose titration is essential once insulin therapy initiated 1

Thiazolidinedione Cautions:

• Use pioglitazone with caution in patients with or at risk for congestive heart failure 1, 6
• Associated with fractures and weight gain 1
• Maximum dose 45 mg once daily 6

SGLT2 Inhibitor Warning:

• FDA warning: Risk of ketoacidosis with SGLT2 inhibitors 1
• Patients must stop SGLT2 inhibitor and seek immediate medical attention if symptoms of ketoacidosis develop 1

Metformin Considerations:

• Rarely causes hypoglycemia by itself, but risk increases with inadequate food intake, alcohol, or other glucose-lowering medications 7
• Do not abruptly discontinue oral medications when starting insulin due to risk of rebound hyperglycemia 4

Insulin Injection Technique:

• Use shortest needles (4-mm pen and 6-mm syringe needles) as first-line choice in all patients 4
• Avoid intramuscular injections, especially with long-acting insulins, as severe hypoglycemia may result 4
• Rotate injection sites continuously to prevent lipohypertrophy, which distorts insulin absorption 4

Monitoring Requirements

• Monitor HbA1c every 3 months until glycemic target achieved, then at least twice yearly 2
• Use fasting plasma glucose to titrate basal insulin; use both fasting and postprandial glucose to titrate mealtime insulin 1, 4
• Frequent self-monitoring of blood glucose is essential for effective insulin therapy 1, 4, 5
• Reassess medication regimens every 3-6 months and adjust based on HbA1c, side effects, and patient factors 3