Drugs for Diabetes Oral Agents 03/25/2025

Page 1: Introduction to Endocrine System

• Topic: The Endocrine System: Drugs for Diabetes Mellitus - Oral Agents

• Course Code: NURS 3110

Page 2: Understanding Type 2 Diabetes Mellitus

• Prevalence: 90-95% of diabetes cases are Type 2, non-insulin dependent.

• Pathophysiology:

  • Obesity: Defined as BMI > 30.

  • Insulin Resistance: Target cells unresponsive due to insulin receptor defects.

  • Dyslipidemia:

    • Elevated total cholesterol (> 200)

    • Elevated LDL (> 130)

    • Elevated triglycerides (> 150; >500 strongly linked to hyperglycemia).

• Risks: Consequences parallel those of Type 1 diabetes.

Page 3: iClicker Question

• Characteristic Symptoms Comparison:

  • T1DM:

    • Weight loss

    • DKA

    • Early morning hypoglycemia

  • T2DM:

    • Insulin resistance

    • Central obesity

Page 4: Risks and Complications of Type 2 Diabetes

• Complications:

  • Vascular Damage: Long-term hyperglycemia lead s to heart disease, stroke, chronic renal disease, blindness.

  • Nerve Damage: Ranges from neuropathy to total lack of sensation.

  • Hyperosmolar Hyperglycemic State (HHS):

    • Occurs with insufficient insulin.

    • Symptoms: Blood sugar levels > 600, dehydration, flushed skin.

    • Treatment: Similar to DKA; requires fluids, electrolyte correction, insulin.

Page 5: iClicker Question 7

• Consequences of Chronic Hyperglycemia:

  • 1. Retinal damage

  • 2. Coronary artery disease

  • 3. Peripheral neuropathy

  • 4. Erectile dysfunction

  • 5. Chronic renal disease

Page 6: Diagnosis of Type 2 Diabetes

• Hyperglycemia Definition:

  • Fasting Blood Sugar (FBS) > 125 mg/dL (≥ 2 occasions)

  • Hemoglobin A1C > 6.5%

  • Postprandial glucose > 140 mg/dL

  • Glucose tolerance test > 200 mg/dL (2 hours post-ingestion).

• Symptoms: Lack of weight loss, visual changes, less pronounced 3 P's (polyphagia, polydipsia, polyuria).

Page 7: Medications for Type 2 Diabetes

• Overview:

  • Referred to as oral agents, not all are taken orally; some do not lower blood glucose directly.

• Classes of Medications:

  • Alpha-glucosidase inhibitors

  • Biguanide

  • Incretin mimetics (GLP-1 agonists)

  • Incretin enhancers (DPP-4 inhibitors)

  • Meglitinides

  • Sulfonylureas (1st and 2nd generation)

  • Thiazolidinediones (TZDs)

  • Miscellaneous (SGLT2 Inhibitors)

Page 8: Adult Doses of Medications

• Alpha-glucosidase Inhibitors:

  • Acarbose: PO 25-100 mg tid (max: 300 mg/day)

  • Miglitol: PO 25-100 mg tid (max: 300 mg/day)

• Biguanide (Metformin):

  • Immediate Release: Starting PO 500 mg bid, max: 2550 mg/day

  • Extended Release: Max 2000 mg/day.

• Incretin Mimetics (GLP-1 Agonists):

  • Various dosing based on drug (albiglutide, exenatide, etc.)

  • All administered Subcutaneously.

Page 9: Biguanide (Metformin)

• Description: Only drug in this class; available as IR and ER formulations.

• Mechanism: Decreases hepatic glucose production and improves insulin sensitivity.

• Safety Profile:

  • No hypoglycemia risk.

  • Common Side Effects: GI upset, bitter/metallic taste.

  • Serious Adverse Event: Lactic acidosis due to drug-drug interactions (e.g., alcohol).

Page 10: iClicker Question

• Significant Advantages of Metformin:

  • Cost effectiveness

  • No significant drug-drug interactions

  • Minimal GI side effects

  • No Black Box warning

Page 11: Sulfonylureas

• Description: First drugs for T2DM; stimulate insulin release and enhance receptor sensitivity.

• Generations:

  • First: Chlorpropamide, tolazamide, tolbutamide

  • Second: Glimepiride, glipizide, glyburide.

• Common Side Effects: GI upset, weight gain, dizziness.

• Serious Events: Risk of hypoglycemia, blood dyscrasias.

• Effectiveness: Tends to diminish over time.

Page 12: Incretin Mimetics (GLP-1 Agonists)

• Mechanism: Activate GLP-1 receptor; increase insulin secretion, slow glucose absorption, reduce glucagon action.

• Drugs: Albiglutide, exenatide, liraglutide, among others (subcutaneous route).

• Common Side Effects: GI upset, injection site reactions.

• Serious Events: Pancreatitis, thyroid tumors.

Page 13: Incretin Enhancers (DPP-4 Inhibitors)

• Mechanism: Slow incretin breakdown, enhancing its effects.

• Drugs: Alogliptin, sitagliptin, etc.

• Common Side Effects: Flu-like symptoms, back pain.

• Serious Events: Liver impairment, hypoglycemia in combination therapy.

Page 14: iClicker Question

• Mechanism of Action Comparison:

  • Metformin: Decreases hepatic glucose production.

  • Glimepiride: Stimulates pancreatic insulin release.

  • Liraglutide: Activates incretin receptors.

  • Sitagliptin: Slows incretin breakdown.

Page 15: Thiazolidinediones (TZDs)

• Mechanism: Decreases insulin resistance.

• Drugs: Pioglitazone and rosiglitazone.

• Common Side Effects: Headache, edema, weight gain.

• Serious Events: Liver toxicity, heart failure (Black Box Warning).

Page 16: Sodium-Glucose Co-Transporter 2 (SGLT2) Inhibitors

• Overview: Newest drug class, approved since 2013; promotes glucose excretion in urine.

• Drugs: Canagliflozin, dapagliflozin, and empagliflozin.

• Common Side Effects: Genital yeast infections, urinary tract infections.

• Serious Events: Hypotension, CKD.

Page 17: Alpha-Glucosidase Inhibitors & Meglitinides

• Alpha-Glucosidase Inhibitors:

  • Block absorption of carbohydrates; include acarbose and miglitol.

  • Common Side Effects: GI upset.

  • Serious Events: Hypoglycemia if combined with other agents.

• Meglitinides: Stimulate insulin release with shorter duration (e.g., nateglinide, repaglinide).

  • Common Side Effects: Similar to alpha-glucosidase inhibitors.

Page 18: iClicker Question

• First-line Treatments for T2DM:

  • Metformin

  • Other Options: Glyburide, pioglitazone are second-line; insulin not typically first-line for T2DM.

Page 19: Gestational Diabetes

• Prevalence: ~5% of pregnant women affected; routine screening for all pregnant women.

• Complications:

  • Neonate: fetal macrosomia, neonatal hypoglycemia, and birth trauma.

  • Mother: increased risk for C-section, preeclampsia.

• Treatment Options: Insulin historically, but now include metformin and glyburide considered second-line.

Page 20: Gestational Diabetes (Repeated Information)

• Same as Page 19, with a note about the recurrence rate of ~48%.

Page 21: iClicker Question

• Maternal Risks of Gestational Diabetes:

  • Risk of C-section, potential for long-term health issues.

• Neonate Risks: Shoulder dystocia, potential for trauma during delivery.