What are the common medications for type 2 diabetes management?

Type 2 Diabetes Medication Classes

The primary medication classes for type 2 diabetes include metformin, sulfonylureas, thiazolidinediones, DPP-4 inhibitors, SGLT-2 inhibitors, GLP-1 receptor agonists, and insulin. 1

First-Line Therapy

• Metformin is the preferred initial pharmacologic agent for most adults with type 2 diabetes when lifestyle modifications alone are insufficient 1
• Metformin reduces HbA1c by approximately 1.1-1.2% as monotherapy and has demonstrated cardiovascular benefits including reduced mortality 2, 3
• It is effective, safe, inexpensive, weight-neutral, and carries low hypoglycemia risk 1, 4

Second-Line and Combination Therapy Options

When metformin monotherapy fails to achieve glycemic targets after approximately 3 months, the following medication classes can be added 1:

Sulfonylureas

• Stimulate insulin secretion from pancreatic beta cells 1
• High risk of hypoglycemia and associated with weight gain 1
• Low cost but less favorable side effect profile 1

Thiazolidinediones (TZDs)

• Improve insulin sensitivity 1
• Associated with weight gain, edema, heart failure risk, and bone fractures 1
• Moderate to high cost 1

DPP-4 Inhibitors (Dipeptidyl Peptidase-4 Inhibitors)

• Examples include sitagliptin and linagliptin 1
• Weight-neutral with low hypoglycemia risk 1
• Reduce HbA1c by approximately 0.6-0.8% 1
• Should not be used concurrently with GLP-1 receptor agonists due to lack of additional benefit 1

SGLT-2 Inhibitors (Sodium-Glucose Cotransporter-2 Inhibitors)

• Examples include empagliflozin 5
• Demonstrated 12-26% reduction in atherosclerotic cardiovascular disease risk and 18-25% reduction in heart failure risk 4
• Provide 24-39% reduction in kidney disease progression 4
• Recommended early in patients with established cardiovascular disease, heart failure, or chronic kidney disease 1, 4
• Associated with modest weight loss 1

GLP-1 Receptor Agonists (Glucagon-Like Peptide-1 Receptor Agonists)

• Examples include liraglutide 6
• High-potency formulations result in weight loss exceeding 5% in most patients, often exceeding 10% 4
• Demonstrated cardiovascular and kidney benefits similar to SGLT-2 inhibitors 4
• Recommended early in patients with established cardiovascular disease or at high cardiovascular risk 1, 4
• Common side effects include gastrointestinal symptoms (nausea, diarrhea) 1
• Contraindicated in patients with personal or family history of medullary thyroid carcinoma or multiple endocrine neoplasia type 2 1

Dual GIP/GLP-1 Receptor Agonists

• Newer class with enhanced weight loss effects compared to GLP-1 receptor agonists alone 1, 4
• Provide greater glucose-lowering efficacy 4

Insulin

• Multiple formulations available: basal (long-acting), prandial (rapid-acting), and premixed 1
• Should be initiated regardless of background therapy when HbA1c >10% or blood glucose ≥300 mg/dL, especially if symptomatic 1, 2
• Approximately one-third of patients with type 2 diabetes require insulin during their lifetime 4
• Highest risk of hypoglycemia and weight gain among all medication classes 1

Pediatric Considerations

For youth with type 2 diabetes, approved medication classes are more limited 1:

• Metformin remains first-line therapy 1
• GLP-1 receptor agonists approved for children ≥10 years old 1
• SGLT-2 inhibitors (specifically empagliflozin) recently approved for pediatric use 1
• Insulin for severe hyperglycemia, ketoacidosis, or when A1C ≥8.5% 1

Additional Medication Classes

Meglitinides (Rapid-Acting Secretagogues)

• Can substitute for sulfonylureas in patients with erratic meal schedules 1
• Similar hypoglycemia risk to sulfonylureas 1

Alpha-Glucosidase Inhibitors

• Used in specific clinical situations 1
• Modest glucose-lowering effect 1

Other Agents

• Bromocriptine, colesevelam, and pramlintide have limited roles in specific situations 1

Key Clinical Considerations

• When HbA1c is ≥1.5% above target, dual-combination therapy or more potent agents should be initiated rather than sequential monotherapy 1
• Selection of add-on therapy should prioritize presence of cardiovascular disease, heart failure, or chronic kidney disease, as SGLT-2 inhibitors and GLP-1 receptor agonists provide proven benefits in these populations 1, 4
• Metformin can be safely used with eGFR ≥30 mL/min/1.73m², though dose reduction is recommended when eGFR is 30-45 mL/min/1.73m² 1, 7
• Extended-release metformin formulations improve gastrointestinal tolerability and allow once-daily dosing 1, 8