What are the primary treatment recommendations for patients with Type 1 (T1DM) and Type 2 (T2DM) Diabetes Mellitus (DM)?

Primary Treatment Recommendations for Type 1 and Type 2 Diabetes Mellitus

Type 1 Diabetes Mellitus

Most patients with Type 1 diabetes should be treated with multiple daily injections (MDI) of prandial and basal insulin (3-4 injections per day) or continuous subcutaneous insulin infusion (CSII), using rapid-acting insulin analogues to reduce hypoglycemia risk. 1

Insulin Regimen Structure

• Initiate insulin therapy immediately at diagnosis with a starting total daily dose of 0.5 units/kg/day for metabolically stable patients, divided between basal and prandial insulin 1
• Higher doses (0.4-1.0 units/kg/day) are required during puberty, and patients presenting with diabetic ketoacidosis need higher weight-based dosing initially 1
• Rapid-acting insulin analogues (aspart, lispro, glulisine) are preferred over regular human insulin because they reduce hypoglycemia risk, particularly nocturnal episodes 1
• Long-acting basal insulin analogues are preferred over NPH insulin due to reduced peak profile, extended duration of action, and lower intraindividual variability 2

Insulin Delivery Methods

• MDI versus CSII (insulin pump) show minimal differences in A1C (combined mean difference favoring CSII by only -0.30 percentage point), though CSII may reduce severe hypoglycemia rates in children and adults 1
• Patients successfully using CSII should maintain access to this therapy after age 65 1
• Sensor-augmented pump therapy with threshold suspend feature reduces nocturnal hypoglycemia without increasing HbA1c 1

Patient Education Requirements

• Educate patients on matching prandial insulin doses to carbohydrate intake, premeal blood glucose levels, and anticipated physical activity 1
• Patients who master carbohydrate counting should receive education on fat and protein gram estimation for advanced glycemic management 1

Glycemic Targets

• Target HbA1c <7% (53 mmol/mol) for most nonpregnant adults to reduce microvascular and macrovascular complications 1, 2
• More stringent goals (<6.5%) may be appropriate for patients with short diabetes duration, long life expectancy, and no significant cardiovascular disease, if achievable without significant hypoglycemia 1
• Less stringent goals (<8%) are appropriate for patients with history of severe hypoglycemia, limited life expectancy, advanced complications, or extensive comorbidities 1

Evidence Base

The DCCT demonstrated that intensive insulin therapy (≥3 injections daily or CSII) reduces microvascular complications, and the EDIC follow-up study showed a 57% reduction in cardiovascular events (nonfatal MI, stroke, or CV death) with intensive therapy, with benefits persisting for decades 1

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Type 2 Diabetes Mellitus

Newly diagnosed patients should begin metformin therapy at or soon after diagnosis (if tolerated and not contraindicated) combined with lifestyle modifications including at least 5% weight loss; for severe hyperglycemia (random glucose ≥300 mg/dL or HbA1c ≥10%), initiate basal insulin immediately at 0.2-0.3 units/kg/day along with metformin. 1, 3

Initial Therapy Algorithm

For patients with random glucose consistently >300 mg/dL:

• Start basal insulin (glargine or detemir) at 0.2-0.3 units/kg/day given once daily at bedtime 3
• Simultaneously initiate metformin 500 mg once daily with dinner, increasing by 500 mg every 1-2 weeks up to 2000 mg daily in divided doses 3
• This approach allows rapid glucose normalization and gives beta cells a chance to "rest and recover" 3
• Taper insulin after 2 weeks to 3 months once glucose control is achieved (fasting glucose 80-130 mg/dL), reducing by 10-20% initially and continuing reductions every 3-7 days 3

For patients with HbA1c ≥9-10%:

• Consider immediate insulin initiation, particularly if symptomatic hyperglycemia is present 3, 4
• Insulin is essential when HbA1c ≥10% (≥86 mmol/mol) after optimal use of diet, physical activity, and other antihyperglycemic agents 4

For patients with HbA1c 7.5-9%:

• Insulin should be considered alone or in combination with oral agents when HbA1c ≥7.5% (≥58 mmol/mol) 4

Metformin as Foundation Therapy

• Metformin is the preferred initial pharmacologic agent due to established efficacy, safety profile, low cost, and potential reduction in cardiovascular events and death 1
• Metformin can be continued with declining renal function down to GFR 30-45 mL/min with dose reduction 1
• When combined with insulin, metformin reduces weight gain, lowers insulin dose requirements, and decreases hypoglycemia compared to insulin alone 4

Combination Therapy Escalation

• When monotherapy with a noninsulin agent at maximum tolerated dose fails to achieve or maintain HbA1c target over 3 months, add a second agent 1
• Consider combination of metformin with one of six options: sulfonylurea, thiazolidinedione, DPP-4 inhibitor, SGLT2 inhibitor, GLP-1 receptor agonist, or basal insulin 1
• The preferred method of insulin initiation is adding long-acting basal insulin, once-daily premixed insulin, or twice-daily premixed insulin, alone or combined with GLP-1 RA or other oral agents 4

Insulin Intensification Strategy

• If desired glucose targets are not met with basal insulin, add rapid-acting or short-acting prandial insulin at mealtimes to control postprandial glucose rises 4
• Titrate basal insulin using fasting plasma glucose values; titrate mealtime insulin using both fasting and postprandial glucose values 4
• Oral medications should not be abruptly discontinued when starting insulin due to risk of rebound hyperglycemia 4

Glycemic Targets

• Target HbA1c <7% for most patients, with fasting glucose 80-130 mg/dL and 2-hour post-meal glucose <180 mg/dL to reduce microvascular complications 3
• Check HbA1c at 3 months to assess response to therapy 3

Monitoring Requirements

• Self-monitor blood glucose with fasting and 2-hour post-meal readings daily while on insulin 3
• Weekly follow-up initially is necessary to titrate insulin and assess for hypoglycemia 3
• Provide education on hypoglycemia symptoms and keeping glucose tablets or sugar readily available 3

Common Pitfalls to Avoid

• Do not delay insulin initiation in patients with severe hyperglycemia (glucose >300 mg/dL or HbA1c ≥10%), as this represents glucose toxicity requiring immediate intervention 3, 4
• Avoid intramuscular injections, especially with long-acting insulins, as severe hypoglycemia may result 4
• Rotate injection sites properly to prevent lipohypertrophy, which distorts insulin absorption 4
• Use shortest needles (4-mm pen or 6-mm syringe needles) as first-line choice in all patients—they are safe, effective, and less painful 4