What are diabetes medications?

Diabetes Medications (DEMARDS)

Diabetes medications encompass several classes of drugs that target different aspects of glucose metabolism to control blood sugar levels and reduce morbidity and mortality in patients with diabetes. These medications are essential for managing hyperglycemia and preventing both acute and chronic complications of diabetes 1.

Major Classes of Diabetes Medications

First-Line Therapy

• Metformin: The preferred initial medication for most patients with type 2 diabetes
  • Mechanism: Decreases hepatic glucose production, improves insulin sensitivity
  • Benefits: High efficacy, good safety profile, low cost, potential cardiovascular mortality benefit compared to sulfonylureas
  • Side effects: GI disturbances, rare lactic acidosis (contraindicated in severe illness or kidney dysfunction)
  • Monitoring: Vitamin B12 levels periodically 1, 2

Other Oral Antihyperglycemic Agents

1. Sulfonylureas

   • Mechanism: Stimulate insulin secretion from pancreatic β-cells
   • Benefits: High glucose-lowering efficacy, inexpensive, evidence for reduction in microvascular complications
   • Limitations: Weight gain, hypoglycemia risk, lack of durable effect
   • Examples: Glipizide, glimepiride, gliclazide 1

2. DPP-4 Inhibitors

   • Mechanism: Increase insulin secretion and reduce glucagon secretion in a glucose-dependent manner
   • Benefits: Moderate efficacy, weight neutral, minimal hypoglycemia risk when used as monotherapy
   • Considerations: Dose adjustment needed in renal dysfunction (except linagliptin)
   • Caution: Potential heart failure risk with saxagliptin and alogliptin
   • Examples: Sitagliptin, saxagliptin, linagliptin 1, 3

3. SGLT2 Inhibitors

   • Mechanism: Inhibit glucose reabsorption in the kidney, increasing urinary glucose excretion
   • Benefits: Moderate efficacy, weight loss, cardiovascular benefits (empagliflozin, canagliflozin)
   • Side effects: Genital mycotic infections, risk of volume depletion
   • Cautions: Risk of diabetic ketoacidosis, increased risk of amputation with canagliflozin
   • Examples: Empagliflozin, canagliflozin, dapagliflozin 1

4. Thiazolidinediones (TZDs)

   • Mechanism: Increase insulin sensitivity
   • Benefits: High glucose-lowering efficacy, durability of effect
   • Limitations: Fluid retention, weight gain, potential heart failure risk, bone fracture risk
   • Examples: Pioglitazone, rosiglitazone 1

Injectable Medications

1. GLP-1 Receptor Agonists

   • Mechanism: Stimulate insulin secretion, reduce glucagon secretion, improve satiety, promote weight loss
   • Benefits: High glucose-lowering efficacy, weight loss, cardiovascular benefits (liraglutide)
   • Administration: Subcutaneous injection (daily or weekly formulations)
   • Examples: Semaglutide, dulaglutide, liraglutide, exenatide 1

2. Insulin

   • Types:
     • Basal insulin: Long-acting (glargine, detemir, degludec) or intermediate-acting (NPH)
     • Bolus/prandial insulin: Rapid-acting (lispro, aspart, glulisine) or short-acting (regular)
     • Premixed formulations
   • Considerations: Dose titration based on self-monitoring, risk of hypoglycemia
   • Initiation: Usually with basal insulin at 10 units/day or 0.1-0.2 units/kg/day 1

Less Commonly Used Medications

• Meglitinides (repaglinide)
• Alpha-glucosidase inhibitors
• Amylin mimetics (pramlintide)
• Dopamine-2 agonists (bromocriptine)
• Bile acid sequestrants (colesevelam) 1

Medication Selection Algorithm

1. Initial Therapy:

   • Start with metformin unless contraindicated
   • If HbA1c ≥9%, consider dual therapy initially
   • If HbA1c ≥10% with symptoms, consider insulin-based regimen 1

2. Add-on Therapy (if target not achieved after ~3 months):

   • Consider patient-specific factors:
     • Cardiovascular disease: Prefer SGLT2 inhibitor or GLP-1 receptor agonist with proven CV benefit
     • Heart failure risk: Avoid TZDs and certain DPP-4 inhibitors (saxagliptin, alogliptin)
     • Weight concerns: Prefer GLP-1 receptor agonist or SGLT2 inhibitor
     • Hypoglycemia risk: Avoid sulfonylureas
     • Cost considerations: Consider sulfonylureas if cost is major factor 1

3. Injectable Therapy:

   • If oral therapy inadequate, consider:
     • GLP-1 receptor agonist before insulin when possible
     • Basal insulin with continued metformin and possibly other agents
     • Combination injectable therapy (basal insulin + GLP-1 receptor agonist or prandial insulin) 1

Important Considerations

• Cost: Significant price variations exist between medication classes, with newer agents generally more expensive than older options 1
• Cardiovascular outcomes: SGLT2 inhibitors (empagliflozin, canagliflozin) and GLP-1 receptor agonists (liraglutide) have demonstrated cardiovascular benefits 1
• Monitoring: Regular assessment of glycemic control (HbA1c every 3 months until target achieved) 1
• Medication errors: Be vigilant about potential errors in prescribing, dispensing, or administration of diabetes medications 4

Common Pitfalls to Avoid

• Delaying insulin when clearly needed (severe hyperglycemia, symptoms)
• Using insulin as a threat rather than a therapeutic option
• Failing to adjust therapy when targets are not met
• Neglecting to consider cardiovascular and renal benefits of newer agents
• Overlooking potential drug interactions, especially with insulin and sulfonylureas
• Not educating patients about hypoglycemia recognition and management when using insulin or insulin secretagogues 1