Injectable Drugs for Diabetes

Growth at Insulin Injection Sites

• Lipohypertrophy is the growth of tissue at insulin injection sites, commonly due to repeated needle use in the same area.
• Scarring and inflammation can occur with repeated insulin injections, impacting absorption and efficacy.

Factors Contributing to Lipohypertrophy

• Repeatedly injecting insulin at the same site significantly contributes to the development of lipohypertrophy.
• The type of needle (short versus long) and injection frequency do not significantly contribute to this condition.

Risk Reduction Strategies

• Rotating injection sites regularly reduces the risk of developing lipohypertrophy.

Insulin Syringe Size

• Insulin syringes are typically marked in 1-2 unit intervals for precision in dosing.
• A 0.5 mL syringe is suitable for administering a 50-unit dose.
• The common needle gauge for insulin syringes is between 28-32 gauge.

Insulin Pen Needle Size

• Insulin pen needles must be ordered separately and are not typically included with the pen.
• Common needle lengths for insulin pen needles range from 4-12.7 mm.
• A higher gauge number indicates a thinner needle.

Insulin Effects on the Body

• GLUT4 is the primary transporter for insulin-mediated glucose uptake in skeletal muscle and adipose tissue.
• Insulin increases protein synthesis and promotes triglyceride storage in adipose tissue.
• It decreases protein catabolism and increases both triglyceride and VLDL synthesis.
• Insulin’s primary role in the liver is to enhance glucose storage as glycogen.

Regulation of Blood Glucose

• Glucagon, secreted by alpha cells in the pancreas, plays a role in glucose regulation.
• GLP-1 hormone helps attenuate glucose spikes after meals and breaks down through DPP-4 enzyme.

Indications for Insulin Therapy

• Insulin therapy is indicated for Type 1, Type 2, secondary diabetes, and gestational diabetes.
• Modern insulin is produced using recombinant DNA technology, reducing the risk of allergic reactions compared to animal-based insulin.

Insulin Degradation and Metabolism

• The liver deactivates around 20-50% of insulin, while the kidneys also play a crucial role in insulin metabolism.
• In end-stage renal disease, insulin dosing should be decreased due to reduced clearance.

Insulin Administration and Absorption

• Intravenous insulin is typically used for patients with uncontrolled diabetes in a hospital setting.
• The abdomen provides the most rapid absorption for subcutaneous insulin injections.
• Rotating injection sites helps prevent lipodystrophy complications.

Lipoatrophy and Lipohypertrophy

• Lipoatrophy is characterized by loss of subcutaneous fat at injection sites, often due to repeated injections in the same location.
• Newer insulin analogs have been associated with a decreased incidence of lipoatrophy.

Types of Insulin

• Short-acting insulin is distinguished by its onset of action compared to long-acting insulin.
• U-100 concentration is the most commonly used insulin concentration.
• Long-acting insulin is utilized to control fasting blood glucose levels.

Endogenous Insulin Production

• The pancreas releases insulin at a blood glucose level of approximately 140 mg/dL.
• Insulin secretion begins about 90 seconds after increased blood glucose levels post-meal.
• Insulin production is responsive to food intake and blood glucose levels rather than being constant.

Common Types of Insulin

• Humalog is a rapid-acting insulin example.
• Rapid-acting insulin is typically used during mealtimes to manage postprandial glucose levels.
• Long-acting insulin, like Lantus, is categorized as "basal" insulin.

Rapid-Acting Insulin

• Apidra is the insulin with the fastest onset of action.
• Rapid-acting insulin should be injected 15 minutes before meals.
• The duration of action for rapid-acting insulin like NovoLog is approximately 3-5 hours.

Short-Acting Insulin

• Humulin R is recognized as a short-acting insulin.
• Regular insulin, a short-acting type, has an onset of action within 30-60 minutes.
• Regular insulin is frequently administered intravenously in hospital settings for managing Diabetic Ketoacidosis (DKA).

Intermediate-Acting Insulin (NPH)

• Humulin N is classified as intermediate-acting insulin.
• NPH insulin requires gentle rolling of the vial to distribute the suspension before injection.
• Intermediate-acting insulin like NPH typically reaches peak effect within 4-10 hours.

Long-Acting Insulin

• Lantus is a long-acting insulin that is considered "peakless," mimicking basal insulin production.
• Tresiba has the longest duration of action among long-acting insulins, lasting up to 42 hours.
• Mixing long-acting insulins like Lantus or Tresiba with other insulins can inactivate them.

NPH Insulin (Additional)

• NPH insulin has a milky appearance and requires gentle rolling before injection.
• It is typically administered twice daily.
• A common complication associated with NPH insulin is hypoglycemia.

Rapid-Acting Insulin - Vial & Pen Forms

• Apidra, or insulin glulisine, is a notable example of rapid-acting insulin.
• The typical onset of action for rapid-acting insulins like Humalog or NovoLog is 10-30 minutes.
• Rapid-acting insulin generally has a duration of 3-5 hours in the body.
• It should be administered 15 minutes before meals or immediately after.
• Rapid-acting insulin is primarily used for postprandial glucose control.
• It can be administered subcutaneously (e.g., via an insulin pump) or via intravenous infusion.

Insulin Titration and Adjustment

• In case of hypoglycemia during basal insulin titration with no clear cause, reduce the insulin dose by 4 units or 10-20%.

Combination Insulin Products

• Humalog Mix 75/25 typically contains 75% insulin lispro protamine and 25% insulin lispro.
• Combination products help control both fasting and postprandial blood glucose levels.
• Glargine/Lixisenatide therapy combines long-acting insulin with a GLP-1 receptor agonist.

Inhaled Insulin (Afrezza)

• Afrezza primarily targets postprandial hyperglycemia.
• Major contraindication includes COPD or asthma.
• Carries a boxed warning for acute bronchospasm in patients with asthma or COPD.

Insulin Adverse Effects

• Most common adverse effect of insulin therapy is hypoglycemia.
• Lipohypertrophy, an insulin-related complication, is associated with excess weight gain.
• Preventing insulin-induced hypoglycemia can be achieved by ensuring proper meal timing for insulin administration.

Insulin Absorption Factors

• Rate of insulin absorption can be affected by insulin concentration, needle length, and injection site rotation.
• The abdomen is the injection site associated with the most consistent and rapid absorption.
• Rotating injection sites is important to prevent tissue reactions like lipodystrophy.

Insulin Therapy Goals

• Primary goal of basal insulin therapy is to maintain glucose control between meals and overnight.
• Rapid-acting insulin is used for bolus therapy to manage postprandial glucose levels.
• Basal insulin aims for a continuous release of insulin to control fasting glucose levels.

Long-Acting Insulin Properties

• Lantus (insulin glargine) is classified as long-acting insulin with a duration of 20-24 hours.
• Mixing long-acting insulins with other types in the same syringe can inactivate the long-acting insulin.
• Toujeo (insulin glargine U-300) has a longer duration of action, lasting 24-36 hours, whereas Tresiba (insulin degludec) can last up to 42 hours.

Blood Glucose Monitoring

• Frequent blood glucose monitoring is essential during pregnancy, when starting or changing medications, and during illness.
• A downside of frequent monitoring can include high costs and potential for patient depression.
• Patients on multiple daily injections should check blood glucose at least four times a day (qACHS).

Bolus vs. Basal Insulin

• Bolus insulin is used to manage glucose spikes after meals and snacks, while basal insulin controls glucose levels between meals and overnight.
• Bolus insulin should be administered 15-30 minutes before a meal for effective glucose control.

Insulin Therapy Overview

• NPH Insulin: Used in diabetes management; rapid-acting counterparts like insulin lispro are available.
• Insulin Pump Catheter Site: Should be changed every 3 days to maintain effectiveness and hygiene.

Continuous Glucose Monitoring (CGM)

• Real-Time Readings: CGM provides immediate glucose levels, improving management accuracy over traditional fingerstick methods.
• Key Measure TIR: Time in Range (TIR) indicates the effectiveness of glucose management and insulin therapy.
• Device Types: Intermittent scanned CGM (isCGM) involves scanning for glucose levels, unlike real-time CGM which continuously displays readings.

Glucose Monitoring Trends

• Tracking TIR Benefits: Offers insights into the effectiveness of insulin treatments over time.
• Parameter TAR: Stands for Time Above Range, showing periods of elevated glucose levels.
• CGM Advantage: Enhances glycemic control without increasing the risk of hypoglycemia.

Insulin Types and Functions

• Basal Insulin: Primarily controls fasting blood glucose levels, providing steady insulin release throughout the day.
• Rapid-Acting Insulin: Commonly used to cover mealtime glucose spikes, addressing post-meal increases.
• Combination Use: A dual approach of basal and bolus insulin supports stable blood glucose between meals and during eating.

Blood Glucose Monitoring Benefits

• Frequent Monitoring: Aids in tracking how lifestyle choices affect blood sugar levels rather than reducing insulin dependency.
• Motivation Factor: Immediate feedback from monitoring can encourage better lifestyle decisions.
• Psychological Considerations: Constant monitoring may lead to depression due to an increased focus on diabetes management.

When to Monitor Blood Glucose

• Critical Situations: Essential to monitor blood glucose while fasting or during illness to prevent complications.
• Pregnancy Monitoring: Increased vigilance is necessary to detect gestational diabetes and minimize risks.
• Occupational Needs: Certain professions, like truck driving, require heightened monitoring to avoid hypoglycemia-related incidents.

Insulin Pump Therapy

• Flexibility: Insulin pumps offer greater flexibility in managing meals and activities compared to traditional methods.
• Insulin Type: Rapid-acting insulin is utilized for both basal and bolus delivery in pump therapy.
• Potential Risks: Increased risk of catheter site infections remains a concern with pump use.

Insulin Pump Mechanics

• CSII Function: Continuous subcutaneous insulin infusion (CSII) delivers tailored basal and bolus doses based on self-monitoring of blood glucose.
• Insulin Approval for Pumps: Insulin lispro is specifically approved for pump use due to its favorable pharmacokinetics, making it ideal for real-time insulin delivery.

Continuous Glucose Monitoring (CGM)

• CGM provides real-time glucose levels and trends, aiding in diabetes management.
• The percentage of time glucose levels are within the target range is referred to as Time in Range (TIR).
• Particularly beneficial for patients using multiple daily insulin injections, enhancing their monitoring capabilities.

Monitoring Blood Glucose (Test Strips)

• Test strips must be compatible with the glucose meter to ensure accurate readings.
• Ensuring an adequate supply of test strips improves patient compliance and glycemic control.
• Accuracy of blood glucose test strips can be significantly affected by storage temperature.

Hypoglycemia

• The first step in treating hypoglycemia involves identifying and addressing its underlying cause.
• A common cause of insulin-induced hypoglycemia is skipping meals after insulin administration.
• In cases without a clear cause for hypoglycemia, reducing the insulin dose by 4 units or 10-20% is recommended.

Glucagon in Hypoglycemia

• Glucagon works by stimulating the liver to release stored glucose, crucial in treating severe hypoglycemia.
• The onset time for glucagon’s effects is typically between 10-20 minutes after administration.
• For children under 6 years or weighing less than 25 kg, the recommended glucagon dose for hypoglycemia is 0.5 mg.

Glucagon Administration

• Glucagon can be administered intravenously (IV), intramuscularly (IM), or subcutaneously (SC).
• Intranasal glucagon is considered when IV access is unavailable for hypoglycemia treatment.
• If a patient shows no response to the initial glucagon dose, it can be repeated after 15-20 minutes.

Incretins Overview

• GLP-1 (glucagon-like peptide-1) plays a crucial role in glucose metabolism by stimulating insulin secretion and inhibiting glucagon release.
• The enzyme DPP-4 (dipeptidyl peptidase-4) breaks down GLP-1, diminishing its activity in the body.
• GLP-1 agonists are utilized in diabetes management to decrease food intake and promote satiety.

GLP-1 Agonists (Mechanism of Action)

• GLP-1 agonists manage blood glucose levels by increasing insulin secretion and decreasing glucagon secretion.
• A major benefit of GLP-1 agonist therapy is weight loss, contrasting with many diabetes medications that may cause weight gain.
• GLP-1 agonists have been shown to reduce hemoglobin A1C by approximately 1%.

GLP-1 Agonists Overview

• Exenatide (Byetta®) is derived from the saliva of the Gila monster lizard.
• Liraglutide (Victoza®) has proven effectiveness in reducing major cardiovascular events and mortality in type 2 diabetes patients.
• Dulaglutide (Trulicity®) is a once-weekly GLP-1 agonist effective for type 2 diabetes and cardiovascular risk reduction.

Semaglutide Variants

• Rybelsus® is the oral form of semaglutide used for the treatment of type 2 diabetes.
• Wegovy® is approved for weight management in patients with obesity and cardiovascular disease.
• Tirzepatide (Mounjaro®) acts as both a GLP-1 receptor agonist and a GIP receptor agonist.

Cardiovascular Benefits of GLP-1 Agonists

• GLP-1 agonists are associated with decreased triglyceride levels by 20% or more.
• They improve endothelial function primarily through vasodilation.
• C-reactive protein (CRP), a marker of cardiovascular health, is reduced by GLP-1 agonists.

Indications for GLP-1 Agonists

• GLP-1 agonists are indicated for the management of type 2 diabetes only.
• They can be combined with basal insulin and metformin to help manage postprandial glucose control.
• A significant benefit of GLP-1 agonists is the reduction of postprandial glucose levels in type 2 diabetes patients.

Adverse Effects of GLP-1 Agonists

• Nausea is the most commonly reported gastrointestinal side effect of GLP-1 agonist therapy.
• Approximately 11-50% of patients may experience nausea as a side effect.
• Pancreatitis is a rare but serious adverse effect associated with GLP-1 agonists.

Contraindications for GLP-1 Agonists

• Gastroparesis is a contraindication for GLP-1 agonist therapy.
• Patients with a history of pancreatitis should avoid GLP-1 agonists.
• Caution is advised when using Exenatide in patients with renal insufficiency due to potential gastrointestinal side effects.

Amylin Analog (Pramlintide)

• Pramlintide (Symlin®) is an amylin analog that primarily slows gastric emptying, reducing postprandial glucose spikes.
• Administration method is via subcutaneous (SC) injection, not oral or through IV.
• Pramlintide assists in reducing caloric intake, potentially leading to weight loss.

Pramlintide Side Effects

• Common side effect includes severe hypoglycemia, especially in insulin-treated patients.
• When starting pramlintide therapy in insulin users, mealtime insulin doses should be decreased by 50% to mitigate hypoglycemia risk.
• Monitoring blood glucose levels closely after meals is advised to manage and minimize hypoglycemic events during initiation of therapy.

Indications for Pramlintide

• Indicated for patients with type 1 and type 2 diabetes who are currently using insulin.
• Not approved for use in gestational diabetes, type 2 diabetes without insulin, or prediabetes patients.