Oral Hypoglycemics II
Thiazolidinediones · DPP-4 Inhibitors · Alpha-Glucosidase Inhibitors
Class Comparison: Mechanisms and Key Features
ClassExamplesMechanismHypo RiskPrimary Adverse Effect
Thiazolidinediones Pioglitazone, rosiglitazone PPAR-gamma agonism → insulin sensitization None Fluid retention, weight gain, heart failure, fractures, bladder cancer (pioglitazone)
DPP-4 inhibitors Sitagliptin, linagliptin, saxagliptin Block DPP-4 → raise incretin levels → glucose-dependent insulin secretion None Nasopharyngitis; saxagliptin: heart failure hospitalization risk
Alpha-glucosidase inhibitors Acarbose, miglitol Inhibit brush border enzymes → slow carbohydrate absorption None Flatulence, bloating, diarrhea (majority of patients)
Thiazolidinediones (TZDs)
  • Activate PPAR-gamma nuclear receptor
  • Redistribute fat: visceral → subcutaneous
  • Slow onset: 6–12 weeks for full effect
  • Pioglitazone preferred (rosiglitazone restricted)
  • Useful in nonalcoholic steatohepatitis, post-stroke (IRIS)
  • Contraindicated in heart failure (NYHA III–IV)
DPP-4 Inhibitors
  • Block DPP-4 enzyme → GLP-1/GIP not degraded
  • Incretin levels rise 2–3x postprandially
  • Glucose-dependent effect → safe in elderly
  • Weight neutral; HbA1c reduction ~0.5–0.8%
  • Linagliptin: no renal dose adjustment needed
  • Saxagliptin: avoid in heart failure
Alpha-Glucosidase Inhibitors
  • Inhibit sucrase, maltase, glucoamylase
  • Delay carbohydrate digestion → blunt postprandial glucose
  • Take with first bite of each meal
  • Minimal systemic absorption (acarbose)
  • Treat hypoglycemia with glucose tablets — NOT sucrose
  • Avoid in inflammatory bowel disease
Incretin System: How DPP-4 Inhibitors Work
Meal absorbed
→
Intestinal L/K cells release GLP-1 & GIP
→
DPP-4 normally degrades incretins (t½ <2 min)
→
DPP-4 inhibitor blocks degradation
→
Elevated incretins → glucose-dependent insulin secretion ↑, glucagon ↓
Safety Signals by Class
Thiazolidinediones
  • Heart failure (fluid retention)
  • Bone fractures in women
  • Bladder cancer risk (pioglitazone)
  • Rosiglitazone: myocardial infarction risk
DPP-4 Inhibitors
  • Pancreatitis (rare, class effect)
  • Saxagliptin: heart failure hospitalization
  • Upper respiratory infections
  • Cardiovascular outcome trials: neutral (no benefit)
Alpha-Glucosidase Inhibitors
  • Flatulence (majority of patients)
  • Bloating and diarrhea
  • Improve with slow dose titration
  • No systemic adverse effects