Medications for Diabetes Mellitus (DM) – Blood Glucose Lowering

This article will provide detailed information on different types of diabetes medications, focusing on their pharmacologic effects, pharmacokinetics, indications, contraindications, adverse effects, and drug interactions.

I. Classes of Medications for DM

1. Insulin:

a. Pharmacologic Effect:

– Insulin is a hormone produced by the pancreas that plays a crucial role in regulating blood glucose levels.

– Insulin acts on target cells, facilitating glucose entry into cells for energy use.

– Insulin also suppresses glucose production in the liver, contributing to a decrease in blood sugar levels.

b. Pharmacokinetics:

– Insulin is administered subcutaneously or intravenously due to its degradation by digestive enzymes if taken orally.

– Insulin circulates in the bloodstream in its free form.

– Insulin is primarily degraded in target tissues, with the liver metabolizing only about 20-50% of the insulin.

– Insulin is filtered by the glomeruli and reabsorbed in the proximal convoluted tubule.

c. Classification of Exogenous Insulin:

• Based on Kinetics:

– Rapid-acting insulin (e.g., Regular insulin, Crystalline insulin).

– Intermediate-acting insulin (e.g., NPH insulin, Lente insulin).

– Long-acting insulin (e.g., Ultralente insulin, Glargine insulin, Detemir insulin).

• Based on Purity:

– Monopic insulin: highly purified, containing only one type of insulin.

– Monocompose insulin: highly purified, containing one type of insulin combined with a carrier.

• Based on Origin:

– Porcine insulin.

– Bovine insulin.

– Human insulin (recombinant insulin).

d. Adverse Effects:

• Hypoglycemia:

– Symptoms: Hunger, rapid heartbeat, sweating, weakness, coma.

– Note: Hypoglycemia can occur with high insulin doses, missed meals, excessive physical activity, or drug interactions.

• Local injection site reactions:

– Redness, swelling, pain, itching at the injection site.

• Lipodystrophy:

– Atrophy and hypertrophy at the injection site due to frequent injections in the same location.

• Insulin resistance:

– Development of antibodies against insulin, reducing treatment effectiveness.

• Metabolic changes:

– Insulin can affect regulatory processes in the body, for example, electrolyte imbalances, renal dysfunction…

e. Drug Interactions:

• High-dose Acetylsalicylic acid:

– Increased risk of hypoglycemia.

• Non-selective beta-blockers on the heart:

– Inhibit insulin action, reducing the hypoglycemic effect.

• Acute alcohol intoxication:

– Inhibits gluconeogenesis, increasing the risk of hypoglycemia.

f. Indications:

• Emergency insulin therapy:

– Insulin deficiency (as in type 1 diabetes), ketoacidosis.

• Required insulin therapy:

– Non-insulin-dependent diabetes (type 2) in pregnant women.

– Non-insulin-dependent diabetes, but blood sugar remains high after adhering to dietary regimens, in combination with other hypoglycemic medications (biguanides, sulfonylureas).

– Non-insulin-dependent diabetes but blood sugar rises due to stress (severe infection, surgery, myocardial infarction, stroke) to prevent osmotic stress.

– Non-insulin-dependent diabetes with severe complications.

2. Biguanides:

a. Pharmacologic Effect:

– Lower blood glucose in patients with non-insulin-dependent diabetes (type 2), but do not lower blood glucose in healthy individuals.

– Do not stimulate insulin secretion by beta cells.

b. Mechanism of Hypoglycemic Action:

• Inhibits hepatic gluconeogenesis:

– From lactate and pyruvate.

• Increases glucose uptake into cells:

– In peripheral tissues, especially muscles.

• Reduces intestinal glucose absorption:

• Enhances insulin action:

– By increasing insulin receptor binding.

c. Other Effects:

• Anorexia:

• Decreases cholesterol incorporation into arterial lipid deposits:

– Beneficial in preventing and treating atherosclerosis.

d. Pharmacokinetics:

– Oral administration, absorbed in the gut.

– Not metabolized in the liver and does not bind to plasma proteins.

– Half-life of 1.5-3 hours.

– Excreted in feces and urine.

e. Types of Biguanides:

• Metformin.

• Metformin hydrochloride.

• Metformin embonate.

f. Indications:

• Non-insulin-dependent diabetes (type 2), both obese and non-obese.

• Glucose intolerance.

• First-line indication or after failure of sulfonylurea treatment.

g. Contraindications:

• Severe renal, hepatic, cardiac, or arterial disease.

• Not prescribed for patients over 65 years old.

• Pregnant women.

• Severe infections.

• Surgical procedures.

• Replaced by insulin therapy.

h. Adverse Effects:

• Lactic acidosis:

– Dangerous, potentially fatal.

• Anorexia:

• Reduced vitamin B12 and folic acid absorption:

– Can lead to anemia.

• Skin allergies:

i. Drug Interactions:

• Alcohol:

– Increases the risk of lactic acidosis.

• Biguanides:

– Enhances the hypoglycemic effect of sulfonylureas.

3. Sulfonylureas:

a. Classification:

• First generation:

– Tolbutamide.

– Chlorpropamide.

• Second generation:

– Glizipide.

b. Pharmacodynamics:

• Stimulates insulin secretion:

– The drug becomes ineffective if the pancreas loses function.

• Increases insulin sensitivity of target tissues:

– By increasing the number of insulin receptors.

c. Indications:

• Patients with non-insulin-dependent diabetes (type 2) with normal weight.

• Caution with the elderly.

• Used in combination in non-insulin-dependent diabetes patients with increased weight but ineffective biguanides.

d. Contraindications:

• Pregnant women.

• Insulin-deficient diabetes (type 1).

• Severe liver failure.

• Renal failure.

e. Adverse Effects:

• Hypoglycemia:

• Allergies:

– Urticaria, erythema multiforme or papular.

• Gastrointestinal:

– Anorexia, nausea, vomiting, liver disease.

– Chlorpropamide can cause cholestatic jaundice.

• Hematologic:

– Decreased neutrophils or platelets.

– Agranulocytosis, particularly hemolytic anemia.

• Hyponatremia:

• Vasodilation:

• Teratogenesis:

f. Drug Interactions:

• Salicylates, sulfonamides anti-infective:

– Increase hypoglycemic effects.

• Coumarin anticoagulants:

– May inhibit tolbutamide oxidation, increasing drug half-life.

• Probenecid, pyrazole derivatives, salicylates, and some antibacterial sulfonamides:

– Decrease renal excretion of sulfonylureas, thus increasing their effects.

II. General Notes on the Use of Medications for DM

• Always follow your doctor’s instructions:

– Dosage, duration of use, method of administration.

• Monitor blood sugar regularly:

– As instructed by your doctor.

• Appropriate diet and exercise regimen:

– Crucial for controlling DM.

• Monitor for adverse effects:

– Inform your doctor if you experience any side effects.

• Avoid alcohol:

– May increase the risk of hypoglycemia or lactic acidosis.

• Use caution when administering medication to children, pregnant women, and nursing mothers:

– Consult your doctor.

• Carry a diabetes identification card:

– In case of emergency, so that medical personnel can provide timely treatment.

Note: This article is for informational purposes only and does not replace the advice of a healthcare professional.