The "Drugs for Diabetes" chapter in Lippincott's Illustrated Reviews: Pharmacology typically

provides an overview of the pharmacological agents used to treat both Type 1 and Type 2
diabetes, along with their mechanisms of action, therapeutic uses, side effects, and interactions.
Here's a summary:
1. Insulin Therapy
 Type 1 Diabetes: Characterized by the destruction of pancreatic β-cells, requiring insulin
for survival.
 Types of Insulin:
o Rapid-acting insulin (e.g., insulin lispro, aspart, glulisine): Fast onset, used
before meals.
o Short-acting insulin (e.g., regular insulin): Slightly slower onset.
o Intermediate-acting insulin (e.g., NPH insulin): Covers insulin needs for about
half the day or overnight.
o Long-acting insulin (e.g., insulin glargine, detemir): Provides basal insulin
throughout the day.
 Mechanism: Insulin replaces endogenous insulin, facilitating glucose uptake into cells,
reducing blood glucose levels.
2. Oral Hypoglycemic Agents (Primarily for Type 2 Diabetes)
These drugs improve insulin sensitivity, enhance insulin secretion, or decrease glucose
production. Major classes include:
 Biguanides:
o Metformin: Decreases hepatic glucose production and increases insulin
sensitivity. It is first-line therapy for Type 2 diabetes.
o Side effects: Gastrointestinal upset, risk of lactic acidosis (especially in renal
impairment).
 Sulfonylureas:
o Glipizide, glyburide, glimepiride: Stimulate insulin secretion from the pancreas
by closing potassium channels on β-cells.
o Side effects: Hypoglycemia, weight gain.
 Meglitinides:
o Repaglinide, nateglinide: Similar to sulfonylureas but with a rapid onset and
shorter duration, taken before meals to increase insulin release.
o Side effects: Hypoglycemia (less frequent), weight gain.
  Thiazolidinediones (TZDs):
o Pioglitazone, rosiglitazone: Increase insulin sensitivity by activating PPAR-γ
receptors, influencing glucose and lipid metabolism.
o Side effects: Weight gain, fluid retention, risk of heart failure, and bone fractures.
 Dipeptidyl Peptidase-4 (DPP-4) Inhibitors:
o Sitagliptin, saxagliptin, linagliptin: Inhibit the breakdown of incretin hormones,
which increases insulin secretion and decreases glucagon release.
o Side effects: Upper respiratory tract infections, joint pain, rare risk of pancreatitis.
 Sodium-Glucose Co-transporter 2 (SGLT2) Inhibitors:
o Canagliflozin, dapagliflozin, empagliflozin: Promote renal excretion of glucose
by inhibiting glucose reabsorption in the kidney.
o Side effects: Increased risk of urinary tract infections, dehydration, and
ketoacidosis.
 Glucagon-like Peptide-1 (GLP-1) Agonists:
o Exenatide, liraglutide, dulaglutide: Mimic incretin hormones to stimulate
insulin release and inhibit glucagon secretion. They also slow gastric emptying
and reduce appetite.
o Side effects: Nausea, vomiting, risk of pancreatitis.
3. Combination Therapies
 Many patients with Type 2 diabetes may require combinations of the above drugs to
achieve glycemic control. Metformin is often used as a base, with additional agents added
depending on the patient's response and side effect profile.
4. Other Agents
 Amylin Analog (Pramlintide): Used as an adjunct to insulin therapy in both Type 1 and
Type 2 diabetes. It delays gastric emptying, reduces glucagon secretion, and promotes
satiety.
 Glucagon: Used to treat severe hypoglycemia by stimulating hepatic glycogenolysis and
increasing blood glucose levels.
5. Management of Diabetes Complications
 Managing diabetes often involves more than just glycemic control. Drugs for
cardiovascular risk reduction (e.g., statins, ACE inhibitors) are also critical in managing
long-term complications of diabetes, such as heart disease, kidney damage, and
neuropathy.
Key Points:
 Type 1 diabetes requires insulin therapy.
 Type 2 diabetes is treated with a combination of oral hypoglycemic agents and
sometimes insulin as the disease progresses.
 Metformin is the cornerstone of Type 2 diabetes management.
 Newer classes like SGLT2 inhibitors and GLP-1 agonists are becoming more common
due to their cardiovascular and renal benefits.

The drugs used to treat diabetes can be classified into different categories based on their
mechanism of action. Here's a classification:
1. Insulins
Used for Type 1 diabetes and advanced Type 2 diabetes.
 Rapid-acting Insulin:
o Examples: Insulin lispro, insulin aspart, insulin glulisine
o Onset: 10–30 minutes, Duration: 3–5 hours
 Short-acting Insulin:
o Example: Regular insulin
o Onset: 30 minutes, Duration: 6–8 hours
 Intermediate-acting Insulin:
o Example: NPH insulin
o Onset: 1–2 hours, Duration: 12–18 hours
 Long-acting Insulin:
o Examples: Insulin glargine, insulin detemir
o Onset: 1–2 hours, Duration: up to 24 hours
 Ultra-long-acting Insulin:
o Example: Insulin degludec
 o Onset: 1 hour, Duration: over 24 hours
2. Oral Hypoglycemic Agents (Primarily for Type 2 Diabetes)
Biguanides
 Metformin:
o Mechanism: Decreases hepatic glucose production, increases insulin sensitivity.
o First-line therapy for Type 2 diabetes.
Sulfonylureas
 Examples: Glipizide, glyburide, glimepiride
 Mechanism: Stimulate insulin secretion by binding to sulfonylurea receptors on
pancreatic β-cells.
Meglitinides
 Examples: Repaglinide, nateglinide
 Mechanism: Similar to sulfonylureas, but with a shorter action. Stimulates insulin
secretion by closing ATP-sensitive potassium channels.
Thiazolidinediones (TZDs)
 Examples: Pioglitazone, rosiglitazone
 Mechanism: Increase insulin sensitivity by activating PPAR-γ receptors in fat and muscle
tissues.
Dipeptidyl Peptidase-4 (DPP-4) Inhibitors
 Examples: Sitagliptin, saxagliptin, linagliptin, alogliptin
 Mechanism: Inhibit the enzyme DPP-4, which breaks down incretins (GLP-1), thereby
increasing insulin release and decreasing glucagon secretion.
Sodium-Glucose Co-transporter 2 (SGLT2) Inhibitors
 Examples: Canagliflozin, dapagliflozin, empagliflozin
 Mechanism: Block reabsorption of glucose in the kidney, leading to increased glucose
excretion in the urine.
Alpha-glucosidase Inhibitors
 Examples: Acarbose, miglitol
 Mechanism: Inhibit enzymes in the intestines that break down carbohydrates, delaying
glucose absorption and reducing postprandial hyperglycemia.
3. Injectable Non-insulin Agents
Glucagon-like Peptide-1 (GLP-1) Agonists
 Examples: Exenatide, liraglutide, dulaglutide, semaglutide
 Mechanism: Mimic incretin hormones, increasing insulin secretion, decreasing glucagon
release, slowing gastric emptying, and promoting satiety.
Amylin Analogs
 Example: Pramlintide
 Mechanism: Slows gastric emptying, reduces postprandial glucagon secretion, and
promotes satiety.
4. Other Agents
Bile Acid Sequestrants
 Example: Colesevelam
 Mechanism: Reduces blood glucose levels through mechanisms that are not fully
understood, possibly related to glucose absorption or bile acid metabolism.
Dopamine Agonists
 Example: Bromocriptine
 Mechanism: Thought to reset circadian rhythms that influence metabolism, improving
insulin sensitivity.
Glucagon
 Used in emergency treatment of severe hypoglycemia.
 Mechanism: Stimulates glycogenolysis in the liver to increase blood glucose levels.
Classification Summary:
Insulins: Replace or supplement insulin in the body.
Biguanides: Decrease glucose production and increase insulin sensitivity.
Sulfonylureas & Meglitinides: Stimulate insulin secretion from the pancreas.
Thiazolidinediones: Increase insulin sensitivity.
DPP-4 Inhibitors & GLP-1 Agonists: Enhance the incretin effect to increase insulin and
decrease glucagon.
SGLT2 Inhibitors: Promote glucose excretion in the urine.
Alpha-glucosidase Inhibitors: Delay carbohydrate absorption.
Amylin Analogs: Slow gastric emptying and reduce glucagon release.
Other Agents: Involve various mechanisms to reduce blood glucose or improve insulin
sensitivity.