What are the initial management and treatment options for diabetes mellitus?

Initial Management and Treatment of Diabetes Mellitus

Type 2 Diabetes

Start metformin immediately at diagnosis alongside lifestyle modifications for all patients with Type 2 diabetes who have normal renal function, unless they present with severe hyperglycemia or ketoacidosis. 1, 2

Presentation-Based Treatment Algorithm

For patients with ketoacidosis or ketosis:

• Initiate insulin therapy (subcutaneous or intravenous) immediately to correct hyperglycemia and metabolic derangement 1
• Once acidosis resolves, start metformin while continuing subcutaneous insulin 1
• This applies regardless of whether diabetes type is initially certain, as substantial percentages of youth with Type 2 diabetes present with ketoacidosis 1

For patients with marked hyperglycemia (blood glucose ≥250 mg/dL or HbA1c ≥8.5%) without acidosis:

• Begin long-acting insulin at 0.5 units/kg/day while simultaneously initiating metformin 1
• Titrate insulin every 2-3 days based on blood glucose monitoring 1
• This approach allows β-cells to "rest and recover" and may improve long-term treatment adherence 1
• Once glycemic targets are achieved, insulin can be gradually reduced over 2-6 weeks by decreasing doses 10-30% every few days 2

For metabolically stable patients (HbA1c <8.5% and asymptomatic):

• Metformin is the sole initial pharmacologic agent needed 1, 2
• Start at 500 mg daily, increase by 500 mg every 1-2 weeks up to maximum dose of 2000 mg daily in divided doses 1, 3
• Gastrointestinal side effects (abdominal pain, bloating, loose stools) are common initially but typically transient 1, 3

Lifestyle Modifications (Mandatory for All Patients)

Weight loss and physical activity targets:

• Lose at least 5% of baseline body weight 1, 2
• Perform at least 150 minutes of moderate-intensity aerobic activity per week 1, 2
• Include resistance training at least twice weekly 1, 2
• Reduce sedentary time 1, 2

Nutrition therapy:

• Individualized medical nutrition therapy program, preferably delivered by a registered dietitian 1, 2
• Low-fat, reduced-calorie diet 4
• Physical activity can reduce HbA1c by 0.4% to 1.0% and improve cardiovascular risk factors 5

Combination Therapy

When to add a second agent:

• If metformin monotherapy at maximum tolerated dose fails to achieve or maintain HbA1c target after 3 months 1, 2
• For HbA1c ≥9% at diagnosis, consider starting dual therapy immediately to achieve faster glycemic control 1, 2

Second-line agent options (add to metformin):

• GLP-1 receptor agonists (preferred if cardiovascular disease, kidney disease, or high cardiovascular risk present) 5
• SGLT2 inhibitors (preferred if cardiovascular disease, kidney disease, or high cardiovascular risk present) 5
• Sulfonylureas 1
• Thiazolidinediones 1
• DPP-4 inhibitors 1
• Basal insulin 1

The choice should prioritize cardiovascular and renal protection: SGLT2 inhibitors and GLP-1 receptor agonists reduce atherosclerotic cardiovascular disease risk by 12-26%, heart failure risk by 18-25%, and kidney disease progression by 24-39% over 2-5 years 5

For children and adolescents (≥10 years old):

• If glycemic targets not met with metformin, add GLP-1 receptor agonist (if no personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia type 2) 1

Monitoring

• Measure HbA1c every 3 months to evaluate treatment efficacy 2
• For patients on ACE inhibitors, ARBs, or diuretics, monitor serum creatinine/eGFR and potassium at least annually 2
• Metformin can be continued with declining renal function down to GFR 30-45 mL/min, though dose should be reduced 1

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Type 1 Diabetes

Treat all patients with Type 1 diabetes using multiple daily insulin injections (≥3 injections daily) or continuous subcutaneous insulin infusion from diagnosis. 1, 2

Insulin Regimen

• Intensive insulin therapy (≥3 injections per day or insulin pump) reduces microvascular complications and cardiovascular disease compared to 1-2 injections daily 1, 2
• Use insulin analogues rather than regular insulin to reduce hypoglycemia risk 1
• Educate patients on matching prandial insulin doses to carbohydrate intake, preprandial blood glucose levels, and anticipated activity 1, 2

Advanced Technologies

• Continuous glucose monitoring systems significantly reduce severe hypoglycemia risk 1
• Insulin pump therapy with low glucose "suspend" feature reduces nocturnal hypoglycemia without increasing HbA1c 1

Critical Pitfall

When diabetes type is uncertain at presentation (e.g., obese child with ketosis), initially treat with insulin while awaiting pancreatic autoantibody results 1. If autoantibodies are negative, transition to Type 2 diabetes management with metformin; if positive, continue intensive insulin therapy as for Type 1 diabetes 1.