Type 2 Diabetes Management and Medications

Introduction

• Focus is on type 2 diabetes (T2D)
• Key element: insulin resistance leading to insulin deficiency and hyperglycemia

Drugs causing dysglycemia

• Beta-blockers (drugs ending in –olol)
• Corticosteroids (prednisone)
• HMG-CoA Reductase Inhibitors (drugs ending in statin)
• Thiazide or loop diuretics (hydrochlorothiazide, furosemide)
• Protease antiviral medications
• Second-generation antipsychotics (olanzapine, quetiapine)

Goals of therapy

• Control symptoms
• Maintain glycemic control
• Prevent complications
• Manage risk factors (hypertension, obesity, dyslipidemia)

Pharmacologic choices

• Nonpharmacologic interventions (diet, exercise) are essential
• Self-monitoring is important

Insulin

• Human insulin and insulin analogues are preferred
• Classified by onset and duration of action
• Rapid-acting for postprandial injections or insulin pump use
• Long-acting for basal infusion

Insulin adverse effects

• Hypoglycemia is the most common
• Localized fat hypertrophy
• Allergic reactions

Biguanides

• Metformin is generally the first choice for new and uncomplicated T2D
• Decreases hepatic glucose production
• Does not cause weight gain
• Lowers HbA1c by 1-1.5%

Biguanides adverse effects

• Gastrointestinal side effects (nausea, diarrhea, discomfort)
• Lactic acidosis risk in those with hepatic/renal disease
• Vitamin B12 deficiency with long-term use
• Low risk of hypoglycemia as monotherapy

Alpha-glucosidase inhibitors

• Acarbose inhibits intestinal alpha-glucosidases
• Delays starch and disaccharide digestion, reducing postprandial glucose
• Does not significantly affect lactase

Acarbose

• Requires TID dosing
• Effective only with meals
• Lowers HbA1c by 1% or less
• Glucose, not sucrose, should be used for hypoglycemia treatment
• Does not cause weight gain

Acarbose adverse effects

• Gastrointestinal side effects (flatulence, diarrhea, pain, cramps)
• May reduce metformin bioavailability
• Contraindicated in irritable bowel disorders

Dipeptidyl Peptidase-4 Inhibitors

• Generic ending: -gliptin
• Sitagliptin is an example
• Inhibit enzyme responsible for GLP-1 degradation
• Indirectly act as incretin mimetics

Dipeptidyl Peptidase-4 Inhibitors

• Do not seem to alter cardiovascular risk
• Lower HbA1c by 1% or less
• Weight neutral

Dipeptidyl Peptidase-4 Inhibitors adverse effects

• Nasopharyngitis, hypersensitivity reactions
• Rare pancreatitis and joint pain
• Low interaction potential due to minimal cytochrome P450 inhibition
• Low risk of hypoglycemia

Glucagon-like Peptide-1 Receptor Agonists

• Semaglutide and liraglutide are examples
• Direct incretin mimetics by acting on GLP-1 receptors
• Increase insulin secretion, suppress glucagon, slow gastric emptying, increase satiety

Glucagon-like Peptide-1 Receptor Agonists

• Usually subcutaneous injection, but oral semaglutide exists
• Decrease HbA1c by 1-1.5%
• Cause weight loss
• Evidence suggests cardiovascular event prevention in both primary and secondary prevention

Glucagon-like Peptide-1 Receptor Agonists adverse effects

• Common GI side effects, especially nausea initially
• Injection site reactions
• Rare pancreatitis
• Caution in heart rhythm disturbances and severe renal impairment
• Contraindicated in pregnancy and those with medullary thyroid carcinoma or MEN type 2

Sulfonylureas

• Glyburide is an example
• Generic names often begin with gly or gli
• Insulin secretagogues, stimulating both basal and meal-stimulated insulin release
• Generally add-on therapy to metformin, not monotherapy

Sulfonylureas

• Lower HbA1c by 1-1.5%
• Variation within the class regarding effectiveness, hypoglycemia risk, and weight gain
• Glyburide has higher hypoglycemia and weight gain risks
• Cardiovascular event reduction unclear due to lack of evidence

Sulfonylureas adverse effects

• Weight gain
• Prolonged hypoglycemia, especially in elderly or those with renal impairment
• Beta-blockers can mask hypoglycemic symptoms

Meglitinides

• Repaglinide is an example
• Another class of insulin secretagogues
• Shorter duration of action than sulfonylureas
• Similar effects and adverse effects as sulfonylureas
• Lower hypoglycemia risk if meals are missed
• More extensive metabolic drug interactions

Sodium-Glucose Cotransporter 2 Inhibitors

• Canagliflozin is an example
• Prevent glucose reabsorption in the kidneys, leading to enhanced excretion
• Do not cause weight gain (cause weight loss)
• Lower HbA1c by 1% or less

Sodium-Glucose Cotransporter 2 Inhibitors

• Reduce cardiovascular mortality, adverse cardiovascular events, and hospitalization due to heart failure
• Small blood pressure decrease
• Require sufficient kidney function
• Slow progression of nephropathy

Sodium-Glucose Cotransporter 2 Inhibitors adverse effects

• Increased risk of urinary tract infections
• Hypotension due to reduced intravascular volume
• Hyperkalemia
• Diabetic ketoacidosis risk
• Increased hypotension risk when used with loop diuretics

Thiazolidinediones

• Pioglitazone is an example
• Agonists at PPARG receptors in the nucleus (particularly in adipose tissue)
• Influence gene expression, upregulating GLUT4 transporters and lipoprotein lipase
• Enhance glucose reabsorption and triglyceride hydrolysis
• Exact mechanism not fully understood

Thiazolidinediones

• Increase peripheral glucose uptake
• Enhance fat cell insulin sensitivity
• Decrease hepatic glucose output
• Reduce HbA1c by 1-1.5%
• Associated with weight gain

Thiazolidinediones adverse effects

• Increased heart failure risk due to fluid retention and edema
• Fractures (hip and wrist)
• Worsened macular edema
• Health Canada mandates patient counseling and written consent for rosiglitazone

Sample question

• Metformin is generally considered first-line therapy for most patients with type 2 diabetes.

This quiz covers essential topics related to Type 2 diabetes (T2D), focusing on insulin resistance, pharmacologic therapies, and the various medications that can affect glycemic control. You'll learn about the goals of diabetes therapy, nonpharmacologic interventions, and the adverse effects of insulin. Test your knowledge on managing symptoms and preventing complications related to T2D.