Prescribing Antidiabetics

The management of diabetes mellitus, particularly type 2 diabetes (T2DM), involves a combination of lifestyle modifications and pharmacological therapy. Prescribing antidiabetics requires a patient-centered approach, tailored to individual needs, comorbidities, and risk factors. Below is a guide for healthcare professionals on the effective and safe prescription of antidiabetic medications.

1. Goals of Antidiabetic Therapy

• Achieve and maintain glycemic control:
  • HbA1c Target: <7% for most patients (may vary based on age, comorbidities, and individual risk).
  • The ideal HbA1c level for people with diabetes is 48 mmol/mol (6.5%) or below. For people at risk of developing type 2 diabetes, the target level is below 42 mmol/mol (6%)
  • Fasting plasma glucose: 80–130 mg/dL.
  • Postprandial glucose: <180 mg/dL.
• Prevent or delay complications:
  • Microvascular (retinopathy, nephropathy, neuropathy).
  • Macrovascular (cardiovascular disease).
• Minimize side effects, particularly hypoglycemia and weight gain.

2. Classes of Antidiabetic Medications

a. Biguanides

• Drug: Metformin.
• Mechanism:
  • Decreases hepatic glucose production.
  • Improves insulin sensitivity in peripheral tissues.
• Indications:
  • First-line therapy for most T2DM patients.
  • Beneficial in overweight/obese patients due to weight neutrality or mild weight loss.
• Dosage:
  • Start with 500 mg once daily; titrate to 2,000 mg/day.
• Side Effects:
  • Gastrointestinal upset (nausea, diarrhea).
  • Rare risk of lactic acidosis (avoid in renal impairment: eGFR <30 mL/min/1.73m²).
• Key Note: Safe, cost-effective, and reduces cardiovascular risks.

b. Sulfonylureas

• Examples: Glimepiride, Gliclazide, Glipizide.
• Mechanism:
  • Stimulate insulin secretion from pancreatic beta cells.
• Indications:
  • Add-on therapy to metformin.
• Side Effects:
  • Hypoglycemia (especially in elderly or renal impairment).
  • Weight gain.
• Key Note: Effective but use cautiously in patients at risk of hypoglycemia.

c. Dipeptidyl Peptidase-4 (DPP-4) Inhibitors

• Examples: Sitagliptin, Linagliptin, Vildagliptin.
• Mechanism:
  • Inhibit DPP-4, prolonging the action of incretin hormones.
  • Increase insulin secretion and suppress glucagon.
• Indications:
  • Add-on to metformin for patients intolerant to sulfonylureas.
• Side Effects:
  • Nasopharyngitis, headache.
  • Rare cases of pancreatitis.
• Key Note: Weight neutral, low hypoglycemia risk.

d. Sodium-Glucose Cotransporter-2 (SGLT2) Inhibitors

• Examples: Empagliflozin, Dapagliflozin, Canagliflozin.
• Mechanism:
  • Increase glucose excretion in urine by inhibiting renal glucose reabsorption.
• Indications:
  • T2DM with cardiovascular disease or heart failure.
  • Kidney protection in diabetic nephropathy.
• Side Effects:
  • Genital infections (mycotic).
  • Volume depletion (dizziness, hypotension).
• Key Note: Cardiovascular and renal benefits; monitor kidney function.

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

• Examples: Liraglutide, Semaglutide, Exenatide.
• Mechanism:
  • Mimic incretin hormones, stimulating insulin release and reducing appetite.
• Indications:
  • T2DM with obesity (significant weight loss benefit).
  • Cardiovascular risk reduction.
• Side Effects:
  • Nausea, vomiting, diarrhea.
  • Rare cases of pancreatitis.
• Key Note: Injectable; excellent for weight loss and cardiovascular protection.

f. Thiazolidinediones (TZDs)

• Examples: Pioglitazone.
• Mechanism:
  • Enhance insulin sensitivity in muscle and adipose tissue.
• Indications:
  • Add-on therapy in insulin-resistant patients.
• Side Effects:
  • Weight gain, fluid retention (risk of heart failure).
  • Risk of bone fractures.
• Key Note: Avoid in heart failure or liver disease.

g. Insulin

• Types:
  • Rapid-acting (e.g., Aspart, Lispro).
  • Long-acting (e.g., Glargine, Detemir).
  • Premixed.
• Indications:
  • Severe hyperglycemia.
  • Long-term use in type 1 diabetes or advanced T2DM.
• Side Effects:
  • Hypoglycemia.
  • Weight gain.
• Key Note: Tailor regimens based on glucose patterns.

3. Choosing the Right Antidiabetic

a. First-Line Therapy

• Metformin:
  • Unless contraindicated, it remains the gold standard.

b. Add-On Therapy Based on Comorbidities

• Cardiovascular Disease:
  • SGLT2 inhibitors or GLP-1 receptor agonists.
• Heart Failure:
  • SGLT2 inhibitors.
• Chronic Kidney Disease:
  • SGLT2 inhibitors or GLP-1 receptor agonists.
• Obesity:
  • GLP-1 receptor agonists.

c. Considerations for Specific Populations

• Elderly:
  • Avoid sulfonylureas or insulin if possible (hypoglycemia risk).
• Pregnancy:
  • Insulin is the preferred treatment.
  • Metformin and glyburide may be used with caution.
• Renal Impairment:
  • Avoid metformin if eGFR <30 mL/min/1.73m².
  • Use linagliptin or GLP-1 receptor agonists cautiously.

4. Monitoring and Follow-Up

• Blood Glucose Monitoring:
  • Self-monitoring for patients on insulin or prone to hypoglycemia.
• HbA1c Testing:
  • Every 3–6 months to assess long-term control.
• Side Effect Monitoring:
  • Renal function (metformin, SGLT2 inhibitors).
  • Liver enzymes (TZDs).
  • Symptoms of hypoglycemia (sulfonylureas, insulin).

5. Patient Counselling

a. Adherence:

• Stress the importance of regular medication use and not skipping doses.

b. Hypoglycemia Risk:

• Educate patients on symptoms (dizziness, sweating, shakiness) and how to manage episodes.

c. Lifestyle Modifications:

• Emphasize the role of diet, exercise, and weight management in diabetes control.

d. Side Effects:

• Inform about common side effects and when to seek medical attention (e.g., signs of infection with SGLT2 inhibitors).

e. Regular Monitoring:

• Encourage adherence to follow-up visits and routine tests.

6. Summary Table

Class	Advantages	Disadvantages	Key Indications
Metformin	Cost-effective, safe	GI upset, lactic acidosis	First-line, overweight patients
Sulfonylureas	Potent glucose lowering	Hypoglycemia, weight gain	Add-on therapy
DPP-4 Inhibitors	Weight neutral, low hypoglycemia	Rare pancreatitis	Add-on therapy
SGLT2 Inhibitors	CV/renal protection, weight loss	Genital infections	CKD, CVD, HF
GLP-1 Receptor Agonists	Weight loss, CV benefit	Injectable, GI upset	Obesity, high CV risk
TZDs	Insulin sensitization	Weight gain, fluid retention	Insulin resistance
Insulin	Universal glucose control	Hypoglycemia, weight gain	Severe hyperglycemia

Conclusion

Antidiabetic therapy must be individualized to meet the patient’s glycemic goals, address comorbidities, and minimize adverse effects. A patient-centered approach, regular monitoring, and comprehensive patient counselling ensure better outcomes and improved quality of life.