What are the recommended medications for treating type 1 and type 2 diabetes?

Medications for Diabetes

Type 1 Diabetes

For type 1 diabetes, insulin is the only essential and FDA-approved therapy, administered as multiple daily injections (MDI) or continuous subcutaneous insulin infusion (CSII), with insulin analogues preferred over human insulin to reduce hypoglycemia risk. 1

Insulin Regimen Structure

• Use MDI with 3-4 injections daily of basal and prandial insulin, or use CSII (insulin pump therapy). 1
• Match prandial insulin dosing to carbohydrate intake, premeal blood glucose levels, and anticipated physical activity. 1
• For most patients, especially those at elevated risk of hypoglycemia, use insulin analogues rather than human insulin. 1

Basal Insulin Selection

• Long-acting insulin analogues (glargine, detemir, degludec) are preferred over NPH insulin because they reduce severe hypoglycemia risk by 35-63% and provide more predictable glucose control. 1, 2
• Human NPH insulin remains an acceptable alternative when cost is prohibitive, though it carries higher hypoglycemia risk. 1
• For patients with frequent nocturnal hypoglycemia or hypoglycemia unawareness, consider sensor-augmented pump therapy with low glucose threshold suspend feature. 1

Prandial Insulin Selection

• Use rapid-acting insulin analogues (aspart, lispro, glulisine) before meals, administered 0-15 minutes prior to eating. 3, 4
• These are preferred over regular human insulin due to better postprandial glucose coverage and reduced delayed hypoglycemia. 3

Adjunctive Therapies (Limited Role)

• Pramlintide is the only FDA-approved adjunctive therapy for type 1 diabetes in adults, causing weight loss and reduced insulin requirements, but requires concurrent reduction of prandial insulin to prevent severe hypoglycemia. 1
• Metformin added to insulin may reduce insulin requirements by 6.6 units/day and modestly improve weight and lipids, but does not improve A1C (reduction only 0.11%, P=0.42). 1
• GLP-1 agonists and DPP-4 inhibitors are NOT FDA-approved for type 1 diabetes, though under investigation. 1
• SGLT2 inhibitors are NOT FDA-approved for type 1 diabetes and carry significant risk of euglycemic diabetic ketoacidosis; the FDA issued specific warnings about this complication. 1

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Type 2 Diabetes

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

Initial Therapy Algorithm

• Begin with lifestyle modifications (weight loss, exercise) plus metformin monotherapy. 1
• Metformin can be safely used with eGFR ≥30 mL/min/1.73 m². 1
• If A1C ≥9% or blood glucose ≥300 mg/dL with symptoms, consider initiating insulin therapy (with or without additional agents) immediately. 1
• If A1C is ≥1.5% above target at diagnosis, consider initiating dual therapy from the start. 1

Second-Line Therapy Selection (When Metformin Fails)

The choice of second agent depends critically on comorbidities, particularly established cardiovascular disease or heart failure. 1

For Patients WITH Established Cardiovascular Disease:

• Add an SGLT2 inhibitor OR a GLP-1 receptor agonist with proven cardiovascular benefit (empagliflozin, liraglutide based on EMPA-REG and LEADER trials). 1
• These agents reduce composite outcomes for myocardial infarction, stroke, and cardiovascular death. 1

For Patients WITH Heart Failure or High Heart Failure Risk:

• SGLT2 inhibitors are preferred due to heart failure benefits. 1

For Patients WITHOUT Cardiovascular Disease:

When metformin alone fails after ~3 months, add one of the following based on patient-specific factors 1:

• Sulfonylureas: Effective A1C lowering but higher severe hypoglycemia risk (OR 7.14 compared to DPP-4 inhibitors, OR 11.11 compared to SGLT2 inhibitors). 1
• DPP-4 inhibitors: Lower hypoglycemia risk (OR 0.14 vs sulfonylureas), modest weight loss, but slightly less A1C reduction (0.12-0.19% less than sulfonylureas/TZDs). 1
• SGLT2 inhibitors: Lowest hypoglycemia risk (OR 0.09 vs sulfonylureas), promote weight loss, reduce blood pressure. 1
• TZDs: Effective A1C lowering but cause weight gain and increase fracture risk. 1
• GLP-1 receptor agonists: Effective A1C lowering, promote weight loss, injectable. 1
• Basal insulin: Most effective for severe hyperglycemia but causes weight gain. 1

Third-Line Therapy

• If metformin plus one agent fails, introduce human insulin (strong recommendation from WHO). 1
• If insulin is unsuitable (e.g., patient lives alone, cannot self-inject), add a DPP-4 inhibitor, SGLT2 inhibitor, or TZD. 1

Insulin Therapy in Type 2 Diabetes

• Start with once-daily basal insulin (NPH, glargine, detemir, or degludec) added to metformin. 1, 3
• Long-acting analogues (glargine, detemir) reduce severe hypoglycemia by 35-63% compared to NPH insulin, though A1C lowering is equivalent. 1
• Detemir causes less weight gain (1.26 kg less than NPH). 1
• If basal insulin alone is insufficient, add a GLP-1 receptor agonist before advancing to multiple daily injections. 1, 2
• Fixed-ratio combinations (insulin degludec/liraglutide) are available to simplify treatment. 2
• When adding prandial insulin, use rapid-acting analogues at mealtimes. 3
• Titrate basal insulin using fasting plasma glucose; titrate prandial insulin using both fasting and postprandial glucose. 3

Important Caveats

• Continue metformin when adding insulin; it reduces insulin requirements, limits weight gain, and decreases hypoglycemia compared to insulin alone. 3
• Discontinue sulfonylureas and DPP-4 inhibitors when starting combination injectable therapy. 2
• Monitor vitamin B12 levels periodically in metformin-treated patients, especially those with anemia or peripheral neuropathy. 1
• Reassess A1C approximately 3 months after any therapy change and intensify if target not achieved. 1
• Do not abruptly discontinue oral medications when starting insulin due to rebound hyperglycemia risk. 3