What diabetes mellitus (DM) medications should be given?

Diabetes Medication Selection

The choice of diabetes medications depends critically on diabetes type, presentation severity, and patient age—with metformin as first-line for stable type 2 diabetes, insulin for type 1 or severe hyperglycemia, and GLP-1 receptor agonists or SGLT2 inhibitors as preferred add-ons when metformin fails to achieve glycemic targets. 1

Initial Assessment and Medication Selection Algorithm

For Adults with Type 2 Diabetes

Start with metformin as the foundational pharmacologic agent when renal function is normal and the patient is metabolically stable 1. Metformin should be prioritized because it is weight-neutral or promotes modest weight loss, which is critical given that over 90% of adults with type 2 diabetes have obesity 1.

For patients with obesity and type 2 diabetes, prioritize glucose-lowering medications based on weight effects 1:

• Highest efficacy for both glucose lowering and weight loss: Tirzepatide and semaglutide (GLP-1 receptor agonists) 1
• Moderate efficacy: Dulaglutide, liraglutide, and extended-release exenatide 1
• Weight-neutral options: SGLT2 inhibitors, DPP-4 inhibitors, metformin 1
• Avoid or minimize: Insulins, sulfonylureas, and thiazolidinediones due to weight gain 1

For Children and Adolescents with Type 2 Diabetes

The approach differs significantly based on A1C level and presence of acidosis 1:

If A1C <8.5% without acidosis or ketosis 1:

• Initiate metformin as first-line therapy
• Titrate up to 2,000 mg per day as tolerated
• Add lifestyle management and diabetes education

If A1C ≥8.5% without acidosis 1:

• Start metformin immediately
• Add long-acting insulin at 0.5 units/kg/day
• Titrate insulin every 2-3 days based on blood glucose monitoring

If acidosis, DKA, or hyperosmolar hyperglycemic state is present 1:

• Manage with intravenous insulin until acidosis resolves
• Then transition to subcutaneous insulin as for type 1 diabetes
• Once metabolically stable, initiate metformin

When glycemic goals are not met on metformin alone 1:

• Add GLP-1 receptor agonist (liraglutide approved for age ≥10 years) or empagliflozin (SGLT2 inhibitor) 1
• Prioritize and maximize noninsulin medications before escalating insulin doses to minimize weight gain 1
• If insulin is needed and basal insulin alone is insufficient, add prandial insulin; total daily dose may exceed 1 unit/kg/day 1

Insulin Therapy Protocols

When Insulin is Required

For severe hyperglycemia (glucose >300 mg/dL) with metabolic derangement 2:

• Begin with priming dose of regular insulin 0.1 units/kg IV bolus
• Follow with continuous IV infusion at 0.1 units/kg/hour
• Target glucose reduction of 50-75 mg/dL per hour
• Continue until glucose <200 mg/dL and metabolic stability achieved

For basal insulin initiation in type 2 diabetes 1:

• Long-acting basal analogs (U-100 glargine, detemir, U-300 glargine, or degludec) reduce hypoglycemia risk compared to NPH insulin
• Longer-acting analogs (U-300 glargine or degludec) have lower nocturnal hypoglycemia risk than U-100 glargine

For mealtime insulin coverage 3, 4:

• Short-acting insulin analogs should be given within 15 minutes before meals or immediately after 4
• Initial dosing: 4 units per meal or 0.1 units/kg per meal 3
• Total daily insulin requirement typically ranges 0.5-1 unit/kg/day 4

Insulin Tapering Protocol

When patients on insulin therapy meet glycemic targets 1:

• Taper insulin over 2-6 weeks
• Decrease insulin dose by 10-30% every few days
• Continue metformin and/or other glucose-lowering medications during taper

Critical Pitfalls to Avoid

Do not delay insulin therapy in patients with marked hyperglycemia (glucose ≥250 mg/dL, A1C ≥8.5%) who are symptomatic with polyuria, polydipsia, or weight loss 1. These patients require immediate basal insulin while metformin is initiated.

Avoid overbasalization with insulin therapy—using higher than necessary basal insulin doses while masking insufficient mealtime insulin coverage 1. Clinical signals include high bedtime-to-morning or preprandial-to-postprandial glucose differences.

Do not abruptly discontinue oral medications when starting insulin due to risk of rebound hyperglycemia 5.

Monitor for hypoglycemia closely when using insulin, especially during dose adjustments, changes in meal patterns, or increased physical activity 1, 4.

GLP-1 receptor agonists should not be used in patients with personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia type 2 1.