What are the initial treatment recommendations for managing type 1 and type 2 diabetes?

Initial Treatment Recommendations for Diabetes Management

Type 2 Diabetes

For newly diagnosed type 2 diabetes, metformin is the preferred initial pharmacological agent and should be started at or soon after diagnosis alongside lifestyle modifications, unless contraindicated or not tolerated. 1

Starting Metformin

• Begin metformin at 500 mg once or twice daily with meals, then titrate gradually to the target dose of 2000 mg daily (1000 mg twice daily) over 2-4 weeks to minimize gastrointestinal side effects. 2
• Ensure eGFR ≥30 mL/min/1.73 m² before initiating metformin, as it is contraindicated below this threshold. 2
• Metformin reduces HbA1c by approximately 1.12% as monotherapy and has cardiovascular benefits including 36% reduction in all-cause mortality and 39% reduction in myocardial infarction. 1, 3

When to Escalate Beyond Metformin Monotherapy

If HbA1c remains above target after 3 months on maximum tolerated metformin dose, add a second agent based on patient comorbidities. 1

• For patients with heart failure or chronic kidney disease, prioritize adding an SGLT-2 inhibitor (such as dapagliflozin). 1
• For patients with increased stroke risk or for whom weight loss is an important goal, prioritize adding a GLP-1 receptor agonist. 1
• Other options include sulfonylureas, thiazolidinediones, or DPP-4 inhibitors, though these are inferior to SGLT-2 inhibitors and GLP-1 agonists for mortality and morbidity outcomes. 1

Immediate Combination Therapy

For patients presenting with HbA1c ≥9%, initiate combination therapy immediately (metformin plus a second agent) rather than waiting 3 months, as monotherapy has low probability of achieving near-normal targets. 1, 2

For patients with marked hyperglycemia (blood glucose ≥300 mg/dL) and/or HbA1c ≥10-12%, especially if symptomatic or showing catabolic features, consider initiating insulin therapy (typically basal insulin) with or without metformin from the outset. 1

Common Pitfalls to Avoid

• Do not delay adding a second agent when HbA1c ≥9%, as the outdated stepwise approach prolongs hyperglycemic exposure and increases risk of complications. 2
• Avoid sulfonylureas as the preferred second agent due to increased hypoglycemia risk and weight gain; prioritize SGLT-2 inhibitors or GLP-1 agonists instead. 1, 2
• When adding SGLT-2 inhibitors or GLP-1 agonists that achieve adequate glycemic control, reduce or discontinue sulfonylureas or long-acting insulins to prevent severe hypoglycemia. 1

Type 1 Diabetes

All patients with type 1 diabetes require insulin therapy from diagnosis, as this is an insulin-deficient state resulting from autoimmune beta-cell destruction. 4

Insulin Regimen

Use a basal-bolus insulin regimen consisting of:

• Basal insulin (long-acting insulin such as glargine or detemir) administered once or twice daily 5, 6

• Prandial insulin (rapid-acting insulin) before each meal 1, 5

• Multiple daily injections (MDI) or continuous subcutaneous insulin infusion (insulin pump) are both effective delivery methods. 1

• For patients with frequent nocturnal hypoglycemia and/or hypoglycemia unawareness, consider a sensor-augmented low glucose threshold suspend pump. 1

Adjunctive Therapies (Limited Role)

• Pramlintide is the only FDA-approved non-insulin therapy for type 1 diabetes in adults, which induces weight loss and lowers insulin dose, but requires concurrent reduction of prandial insulin to reduce severe hypoglycemia risk. 1
• Metformin may be added to insulin therapy in overweight/obese patients with poorly controlled type 1 diabetes to reduce insulin requirements (by approximately 6.6 U/day) and achieve small reductions in weight and cholesterol, though it does not significantly improve HbA1c. 1
• GLP-1 agonists, DPP-4 inhibitors, and SGLT-2 inhibitors are not FDA-approved for type 1 diabetes and have insufficient data to recommend clinical use at this time. 1

Type 2 Diabetes in Youth

For youth with newly diagnosed type 2 diabetes, treatment approach depends on metabolic stability at presentation: 1

Metabolically Stable (HbA1c <8.5%, asymptomatic, no ketosis)

• Metformin is the initial pharmacologic treatment of choice if renal function is normal, titrated up to 2000 mg per day as tolerated. 1

Marked Hyperglycemia (Blood glucose ≥250 mg/dL, HbA1c ≥8.5%) Without Acidosis

• Treat initially with long-acting insulin (starting at 0.5 units/kg/day, titrated every 2-3 days) while metformin is initiated and titrated. 1

Ketosis/Ketoacidosis

• Initiate subcutaneous or intravenous insulin to rapidly correct hyperglycemia and metabolic derangement; once acidosis resolves, start metformin while continuing subcutaneous insulin. 1

Escalation in Youth

• If glycemic targets are not met with metformin (with or without long-acting insulin), add a GLP-1 receptor agonist approved for youth with type 2 diabetes in children ≥10 years old, provided no personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia type 2. 1