Pharmacodynamics

Chemistry

• Insulin is a small protein normally created and released by pancreatic beta cells. 
• Available formulations can be:
  • Human insulin: identical to endogenously produced insulin
  • Analog insulin: altered to create pharmacokinetic advantages

Mechanism of action

• Insulin acts on cells to ↑glucoseGlucoseA primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement.Lactose Intolerance uptake in all tissues, including the: 
  • LiverLiverThe liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood.Liver: Anatomy
  • Skeletal muscle
  • Adipose tissueAdipose tissueAdipose tissue is a specialized type of connective tissue that has both structural and highly complex metabolic functions, including energy storage, glucose homeostasis, and a multitude of endocrine capabilities. There are three types of adipose tissue, white adipose tissue, brown adipose tissue, and beige or “brite” adipose tissue, which is a transitional form.Adipose Tissue: Histology
• This occurs viaglucoseGlucoseA primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement.Lactose Intolerance transporters (GLUTs): 
  • GLUT4 → muscle and adipose
  • GLUT2GLUT2A glucose transport facilitator that is expressed primarily in pancreatic beta cells; liver; and kidneys. It may function as a glucose sensor to regulate insulin release and glucose homeostasis.Digestion and Absorption →liverLiverThe liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood.Liver: Anatomy
• Exogenous insulin is often used to overcomehyperglycemiaHyperglycemiaAbnormally high blood glucose level.Diabetes Mellitus caused by:
  • Insulin deficiency (type 1Type 1Spinal Muscular AtrophydiabetesDiabetesDiabetes mellitus (DM) is a metabolic disease characterized by hyperglycemia and dysfunction of the regulation of glucose metabolism by insulin. Type 1 DM is diagnosed mostly in children and young adults as the result of autoimmune destruction of β cells in the pancreas and the resulting lack of insulin. Type 2 DM has a significant association with obesity and is characterized by insulin resistance.Diabetes Mellitus)
  • Insulin resistanceInsulin resistanceDiminished effectiveness of insulin in lowering blood sugar levels: requiring the use of 200 units or more of insulin per day to prevent hyperglycemia or ketosis.Diabetes Mellitus (type 2Type 2Spinal Muscular AtrophydiabetesDiabetesDiabetes mellitus (DM) is a metabolic disease characterized by hyperglycemia and dysfunction of the regulation of glucose metabolism by insulin. Type 1 DM is diagnosed mostly in children and young adults as the result of autoimmune destruction of β cells in the pancreas and the resulting lack of insulin. Type 2 DM has a significant association with obesity and is characterized by insulin resistance.Diabetes Mellitus)

Physiologic effect

• In theliverLiverThe liver is the largest gland in the human body. The liver is found in the superior right quadrant of the abdomen and weighs approximately 1.5 kilograms. Its main functions are detoxification, metabolism, nutrient storage (e.g., iron and vitamins), synthesis of coagulation factors, formation of bile, filtration, and storage of blood.Liver: Anatomy:
  • ↑ GlycogensynthesisSynthesisPolymerase Chain Reaction (PCR)
  • ↑GlycolysisGlycolysisGlycolysis is a central metabolic pathway responsible for the breakdown of glucose and plays a vital role in generating free energy for the cell and metabolites for further oxidative degradation. Glucose primarily becomes available in the blood as a result of glycogen breakdown or from its synthesis from noncarbohydrate precursors (gluconeogenesis) and is imported into cells by specific transport proteins.Glycolysis
  • ↑LipogenesisLipogenesisDe novo fat synthesis in the body. This includes the synthetic processes of fatty acids and subsequent triglycerides in the liver and the adipose tissue. Lipogenesis is regulated by numerous factors, including nutritional, hormonal, and genetic elements.Metabolic Dysfunction-associated Steatotic Liver Disease (MASLD)
  • ↑ ProteinsynthesisSynthesisPolymerase Chain Reaction (PCR)
  • ↓GlycogenolysisGlycogenolysisThe release of glucose from glycogen by glycogen phosphorylase (phosphorolysis). The released glucose-1-phosphate is then converted to glucose-6-phosphate by phosphoglucomutase before entering glycolysis. Glycogenolysis is stimulated by glucagon or epinephrine via the activation of phosphorylase kinase.Glycogen Metabolism andgluconeogenesisGluconeogenesisGluconeogenesis is the process of making glucose from noncarbohydrate precursors. This metabolic pathway is more than just a reversal of glycolysis. Gluconeogenesis provides the body with glucose not obtained from food, such as during a fasting period. The production of glucose is critical for organs and cells that cannot use fat for fuel.Gluconeogenesis
  • ↓ Conversion of fatty andamino acidsAmino acidsOrganic compounds that generally contain an amino (-NH2) and a carboxyl (-COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins.Basics of Amino Acids toketonesKetonesOrganic compounds containing a carbonyl group =C=O bonded to two hydrocarbon groups.Basics of Carbohydrates
• In muscle:
  • ↑GlycolysisGlycolysisGlycolysis is a central metabolic pathway responsible for the breakdown of glucose and plays a vital role in generating free energy for the cell and metabolites for further oxidative degradation. Glucose primarily becomes available in the blood as a result of glycogen breakdown or from its synthesis from noncarbohydrate precursors (gluconeogenesis) and is imported into cells by specific transport proteins.Glycolysis
  • ↑ ProteinsynthesisSynthesisPolymerase Chain Reaction (PCR)
  • ↑LipogenesisLipogenesisDe novo fat synthesis in the body. This includes the synthetic processes of fatty acids and subsequent triglycerides in the liver and the adipose tissue. Lipogenesis is regulated by numerous factors, including nutritional, hormonal, and genetic elements.Metabolic Dysfunction-associated Steatotic Liver Disease (MASLD)
  • ↑ GlycogensynthesisSynthesisPolymerase Chain Reaction (PCR)
• Inadipose tissueAdipose tissueAdipose tissue is a specialized type of connective tissue that has both structural and highly complex metabolic functions, including energy storage, glucose homeostasis, and a multitude of endocrine capabilities. There are three types of adipose tissue, white adipose tissue, brown adipose tissue, and beige or “brite” adipose tissue, which is a transitional form.Adipose Tissue: Histology:
  • ↑ Triglyceride storage
  • ↓LipolysisLipolysisThe metabolic process of breaking down lipids to release free fatty acids, the major oxidative fuel for the body. Lipolysis may involve dietary lipids in the digestive tract, circulating lipids in the blood, and stored lipids in the adipose tissue or the liver. A number of enzymes are involved in such lipid hydrolysis, such as lipase and lipoprotein lipase from various tissues.Metabolic Dysfunction-associated Steatotic Liver Disease (MASLD)
• On blood levels:
  • ↓GlucoseGlucoseA primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement.Lactose Intolerance
  • ↓ FattyacidsAcidsChemical compounds which yield hydrogen ions or protons when dissolved in water, whose hydrogen can be replaced by metals or basic radicals, or which react with bases to form salts and water (neutralization). An extension of the term includes substances dissolved in media other than water.Acid-Base Balance
  • ↓ KetoacidsAcidsChemical compounds which yield hydrogen ions or protons when dissolved in water, whose hydrogen can be replaced by metals or basic radicals, or which react with bases to form salts and water (neutralization). An extension of the term includes substances dissolved in media other than water.Acid-Base Balance
  • ↓Amino acidsAmino acidsOrganic compounds that generally contain an amino (-NH2) and a carboxyl (-COOH) group. Twenty alpha-amino acids are the subunits which are polymerized to form proteins.Basics of Amino Acids

Pharmacokinetics

AbsorptionAbsorptionAbsorption involves the uptake of nutrient molecules and their transfer from the lumen of the GI tract across the enterocytes and into the interstitial space, where they can be taken up in the venous or lymphatic circulation.Digestion and Absorption

• AbsorptionAbsorptionAbsorption involves the uptake of nutrient molecules and their transfer from the lumen of the GI tract across the enterocytes and into the interstitial space, where they can be taken up in the venous or lymphatic circulation.Digestion and Absorption and onset of action depend on:
  • Mode of administration
  • Site of administration
• Fastest to slowest: 
  • IV > IM > SC
  • Abdomen > arms > buttocks >thighThighThe thigh is the region of the lower limb found between the hip and the knee joint. There is a single bone in the thigh called the femur, which is surrounded by large muscles grouped into 3 fascial compartments.Thigh: Anatomy
• Other factors that may have an effect:
  • Exercise
  • Temperature
  • Local blood supply

Excretion

• Insulin is cleared through thekidneysKidneysThe kidneys are a pair of bean-shaped organs located retroperitoneally against the posterior wall of the abdomen on either side of the spine. As part of the urinary tract, the kidneys are responsible for blood filtration and excretion of water-soluble waste in the urine.Kidneys: Anatomy.
• Dosing may need to be adjusted in individuals withrenal failureRenal failureConditions in which the kidneys perform below the normal level in the ability to remove wastes, concentrate urine, and maintain electrolyte balance; blood pressure; and calcium metabolism. Renal insufficiency can be classified by the degree of kidney damage (as measured by the level of proteinuria) and reduction in glomerular filtration rate.Crush Syndrome.

Classification

Insulin types can be classified based on theirpharmacokineticsPharmacokineticsPharmacokinetics is the science that analyzes how the human body interacts with a drug. Pharmacokinetics examines how the drug is absorbed, distributed, metabolized, and excreted by the body.Pharmacokinetics and Pharmacodynamics:

• Fast acting: 
  • Absorbed quickly
  • Quick peak effect
  • Examples:
    • Lispro
    • Aspart
    • Glulisine
• Short acting: 
  • Still absorbed rapidly
  • Slightly longer peak effect
  • Example: regular
• Intermediate acting: 
  • Absorbed more slowly
  • Lasts longer
  • Example: neutral protamine Hagedorn (NPHNPHNormal pressure hydrocephalus (NPH) is a neurodegenerative disorder characterized by the triad of gait abnormalities, dementia, and urinary urgency or incontinence. Normal pressure hydrocephalus can be either idiopathic or secondary to intraventricular or subarachnoid hemorrhage.Normal Pressure Hydrocephalus)
• Long acting:
  • Absorbed slowly
  • Minimal peak effect (provides a stableplateauPlateauCardiac Physiology effect)
  • Lasts most of the day
  • Examples: 
    • Detemir
    • Glargine
    • Degludec

Indications

DiabetesDiabetesDiabetes mellitus (DM) is a metabolic disease characterized by hyperglycemia and dysfunction of the regulation of glucose metabolism by insulin. Type 1 DM is diagnosed mostly in children and young adults as the result of autoimmune destruction of β cells in the pancreas and the resulting lack of insulin. Type 2 DM has a significant association with obesity and is characterized by insulin resistance.Diabetes Mellitus

Subcutaneous insulin:

• Type 1Type 1Spinal Muscular AtrophydiabetesDiabetesDiabetes mellitus (DM) is a metabolic disease characterized by hyperglycemia and dysfunction of the regulation of glucose metabolism by insulin. Type 1 DM is diagnosed mostly in children and young adults as the result of autoimmune destruction of β cells in the pancreas and the resulting lack of insulin. Type 2 DM has a significant association with obesity and is characterized by insulin resistance.Diabetes Mellitus mellitus:
  • Individuals withtype 1Type 1Spinal Muscular AtrophydiabetesDiabetesDiabetes mellitus (DM) is a metabolic disease characterized by hyperglycemia and dysfunction of the regulation of glucose metabolism by insulin. Type 1 DM is diagnosed mostly in children and young adults as the result of autoimmune destruction of β cells in the pancreas and the resulting lack of insulin. Type 2 DM has a significant association with obesity and is characterized by insulin resistance.Diabetes Mellitus mellitus require insulin replacement at all times.
  • Multiple daily injections can be used to simulate physiologic insulinreleaseReleaseRelease of a virus from the host cell following virus assembly and maturation. Egress can occur by host cell lysis, exocytosis, or budding through the plasma membrane.Virology:
    • Basal (long-acting) insulin is given once or twice daily.
    • Boluses of rapid-acting insulin are given with meals.
  • A continuous insulin infusion (via insulinpumpPumpACES and RUSH: Resuscitation Ultrasound Protocols) with meal-time boluses is also an option.
• Type 2Type 2Spinal Muscular AtrophydiabetesDiabetesDiabetes mellitus (DM) is a metabolic disease characterized by hyperglycemia and dysfunction of the regulation of glucose metabolism by insulin. Type 1 DM is diagnosed mostly in children and young adults as the result of autoimmune destruction of β cells in the pancreas and the resulting lack of insulin. Type 2 DM has a significant association with obesity and is characterized by insulin resistance.Diabetes Mellitus mellitus:
  • Added when oral therapy has failed to provide adequateglucoseGlucoseA primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement.Lactose Intolerance control
  • Usually used in addition to other oral antidiabetic medications (e.g.,metforminMetforminA biguanide hypoglycemic agent used in the treatment of non-insulin-dependent diabetes mellitus not responding to dietary modification. Metformin improves glycemic control by improving insulin sensitivity and decreasing intestinal absorption of glucose.Non-insulinotropic Diabetes Drugs)
  • Indicated for initial therapy when severehyperglycemiaHyperglycemiaAbnormally high blood glucose level.Diabetes Mellitus is noted upon diagnosis
• GestationaldiabetesDiabetesDiabetes mellitus (DM) is a metabolic disease characterized by hyperglycemia and dysfunction of the regulation of glucose metabolism by insulin. Type 1 DM is diagnosed mostly in children and young adults as the result of autoimmune destruction of β cells in the pancreas and the resulting lack of insulin. Type 2 DM has a significant association with obesity and is characterized by insulin resistance.Diabetes Mellitus: preferred therapy for uncontrolledhyperglycemiaHyperglycemiaAbnormally high blood glucose level.Diabetes Mellitus despite diet and activity modifications

IV insulin:

• DiabeticketoacidosisKetoacidosisA life-threatening complication of diabetes mellitus, primarily of type 1 diabetes mellitus with severe insulin deficiency and extreme hyperglycemia. It is characterized by ketosis; dehydration; and depressed consciousness leading to coma.Metabolic Acidosis (DKADKADiabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic state (HHS) are serious, acute complications of diabetes mellitus. Diabetic ketoacidosis is characterized by hyperglycemia and ketoacidosis due to an absolute insulin deficiency.Hyperglycemic Crises)
• Hyperosmolar hyperglycemic stateHyperosmolar hyperglycemic stateA serious complication of type 2 diabetes mellitus. It is characterized by extreme hyperglycemia; dehydration; serum hyperosmolarity; and depressed consciousness leading to coma in the absence of ketosis and acidosis.Hyperglycemic Crises

Other indications

BesidesdiabetesDiabetesDiabetes mellitus (DM) is a metabolic disease characterized by hyperglycemia and dysfunction of the regulation of glucose metabolism by insulin. Type 1 DM is diagnosed mostly in children and young adults as the result of autoimmune destruction of β cells in the pancreas and the resulting lack of insulin. Type 2 DM has a significant association with obesity and is characterized by insulin resistance.Diabetes Mellitus, IV insulin can be used in several other conditions (often in conjunction withdextroseDextroseIntravenous Fluids to maintain euglycemia).

• HyperkalemiaHyperkalemiaHyperkalemia is defined as a serum potassium (K+) concentration >5.2 mEq/L. Homeostatic mechanisms maintain the serum K+ concentration between 3.5 and 5.2 mEq/L, despite marked variation in dietary intake. Hyperkalemia can be due to a variety of causes, which include transcellular shifts, tissue breakdown, inadequate renal excretion, and drugs.Hyperkalemia:
  • Shifts K into cells
  • Temporary treatment used to acutely ↓ K levels
• Hypertriglyceridemia-induced acutepancreatitisPancreatitisInflammation of the pancreas. Pancreatitis is classified as acute unless there are computed tomographic or endoscopic retrograde cholangiopancreatographic findings of chronic pancreatitis. The two most common forms of acute pancreatitis are alcoholic pancreatitis and gallstone pancreatitis.Acute Pancreatitis:
  • ↓ Fatty acidreleaseReleaseRelease of a virus from the host cell following virus assembly and maturation. Egress can occur by host cell lysis, exocytosis, or budding through the plasma membrane.Virology fromadipocytesAdipocytesCells in the body that store fats, usually in the form of triglycerides. White adipocytes are the predominant type and found mostly in the abdominal cavity and subcutaneous tissue. Brown adipocytes are thermogenic cells that can be found in newborns of some species and hibernating mammals.Adipose Tissue: Histology
  • ↑ Triglyceride storage
  • ↓ Triglyceride levels
• Beta-blocker andcalciumCalciumA basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.Electrolytes channel blocker (CCB)toxicityToxicityDosage Calculation:
  • Indicated in hemodynamically unstable individuals refractory to other treatments
  • ↑ Inotropy inmyocytesMyocytesMature contractile cells, commonly known as myocytes, that form one of three kinds of muscle. The three types of muscle cells are skeletal, cardiac, and smooth. They are derived from embryonic (precursor) muscle cells called myoblasts.Muscle Tissue: Histology (affected by CCBtoxicityToxicityDosage Calculation) by ↑glucoseGlucoseA primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement.Lactose Intolerance uptake needed for aerobic metabolism
  • Overcomes insulin deficiency caused by beta-blocker’s effect on thepancreasPancreasThe pancreas lies mostly posterior to the stomach and extends across the posterior abdominal wall from the duodenum on the right to the spleen on the left. This organ has both exocrine and endocrine tissue.Pancreas: Anatomy

Adverse Effects and Contraindications

Adverse effects

• HypoglycemiaHypoglycemiaHypoglycemia is an emergency condition defined as a serum glucose level ≤ 70 mg/dL (≤ 3.9 mmol/L) in diabetic patients. In nondiabetic patients, there is no specific or defined limit for normal serum glucose levels, and hypoglycemia is defined mainly by its clinical features.Hypoglycemia: 
  • Confusion
  • HeadacheHeadacheThe symptom of pain in the cranial region. It may be an isolated benign occurrence or manifestation of a wide variety of headache disorders.Brain Abscess
  • PalpitationsPalpitationsEbstein’s Anomaly
  • TachycardiaTachycardiaAbnormally rapid heartbeat, usually with a heart rate above 100 beats per minute for adults. Tachycardia accompanied by disturbance in the cardiac depolarization (cardiac arrhythmia) is called tachyarrhythmia.Sepsis in Children
  • Diaphoresis
• Weight gain after initiation
• EdemaEdemaEdema is a condition in which excess serous fluid accumulates in the body cavity or interstitial space of connective tissues. Edema is a symptom observed in several medical conditions. It can be categorized into 2 types, namely, peripheral (in the extremities) and internal (in an organ or body cavity).Edema
• AnaphylaxisAnaphylaxisAn acute hypersensitivity reaction due to exposure to a previously encountered antigen. The reaction may include rapidly progressing urticaria, respiratory distress, vascular collapse, systemic shock, and death.Type I Hypersensitivity Reaction
• Injection site:
  • ErythemaErythemaRedness of the skin produced by congestion of the capillaries. This condition may result from a variety of disease processes.Chalazion
  • SwellingSwellingInflammation
  • Lipoatrophy

ContraindicationsContraindicationsA condition or factor associated with a recipient that makes the use of a drug, procedure, or physical agent improper or inadvisable. Contraindications may be absolute (life threatening) or relative (higher risk of complications in which benefits may outweigh risks).Noninvasive Ventilation

• HypokalemiaHypokalemiaHypokalemia is defined as plasma potassium (K+) concentration< 3.5 mEq/L. Homeostatic mechanisms maintain plasma concentration between 3.5-5.2 mEq/L despite marked variation in dietary intake. Hypokalemia can be due to renal losses, GI losses, transcellular shifts, or poor dietary intake.Hypokalemia (insulin drives K+ into cells)
• Hypersensitivity
• HypoglycemiaHypoglycemiaHypoglycemia is an emergency condition defined as a serum glucose level ≤ 70 mg/dL (≤ 3.9 mmol/L) in diabetic patients. In nondiabetic patients, there is no specific or defined limit for normal serum glucose levels, and hypoglycemia is defined mainly by its clinical features.Hypoglycemia

Precautions

Dosing adjustments and close monitoring may be necessary for individuals with:

• Hepatic impairment
• Renal impairment

Drug interactions

• ↑ Hypoglycemic effect with:
  • Other antidiabetic agents
  • Alcohol
  • AndrogensAndrogensAndrogens are naturally occurring steroid hormones responsible for development and maintenance of the male sex characteristics, including penile, scrotal, and clitoral growth, development of sexual hair, deepening of the voice, and musculoskeletal growth.Androgens and Antiandrogens
  • Beta-blockersBeta-blockersDrugs that bind to but do not activate beta-adrenergic receptors thereby blocking the actions of beta-adrenergic agonists. Adrenergic beta-antagonists are used for treatment of hypertension, cardiac arrhythmias, angina pectoris, glaucoma, migraine headaches, and anxiety.Class 2 Antiarrhythmic Drugs (Beta Blockers)
  • Direct-acting antiviral agentsDirect-Acting Antiviral AgentsAntivirals for Hepatitis C forhepatitis CHepatitis CHepatitis C is an infection of the liver caused by the hepatitis C virus (HCV). The infection can be transmitted through infectious blood or body fluids and may be transmitted during childbirth or through IV drug use or sexual intercourse. Hepatitis C virus can cause both acute and chronic hepatitis, ranging from a mild to a serious, lifelong illness including liver cirrhosis and hepatocellular carcinoma (HCC).Hepatitis C Virus
  • MonoamineoxidaseOxidaseNeisseria inhibitors (MAOIsMAOIsMonoamine oxidase inhibitors are a class of antidepressants that inhibit the activity of monoamine oxidase (MAO), thereby increasing the amount of monoamine neurotransmitters (particularly serotonin, norepinephrine, and dopamine). The increase of these neurotransmitters can help in alleviating the symptoms of depression.Monoamine Oxidase Inhibitors)
  • Salicylates
  • Sulfa antibiotics
• ↑ Insulin dosing may be needed with:
  • CorticosteroidsCorticosteroidsChorioretinitis
  • Estrogens/oral contraceptives
  • ThiazideThiazideHeterocyclic compounds with sulfur and nitrogen in the ring. This term commonly refers to the benzothiadiazines that inhibit sodium-potassium-chloride symporters and are used as diuretics.HyponatremiadiureticsDiureticsAgents that promote the excretion of urine through their effects on kidney function.Heart Failure and Chronic Coronary Syndrome Medication
  • Antipsychotics
  • NiacinNiacinA water-soluble vitamin of the B complex occurring in various animal and plant tissues. It is required by the body for the formation of coenzymes nad and NADP. It has pellagra-curative, vasodilating, and antilipemic properties.Lipid Control Drugs

Comparison of Insulins

References

1. Donner, T. (2019). Insulin: Pharmacology, therapeutic regimens, and principles of intensive insulin therapy. Endotext. NCBI Bookshelf. NCBI. Retrieved August 22, 2021, fromhttps://www.ncbi.nlm.nih.gov/books/NBK278938/
2. Weinstock, R. S. (n.d.). General principles of insulin therapy in diabetes mellitus. Uptodate. Retrieved August 2, 2021, fromhttps://www.uptodate.com/contents/general-principles-of-insulin-therapy-in-diabetes-mellitus
3. Durnwald, C. (n.d.). Gestation diabetes mellitus: Glycemic control and maternal prognosis. Uptodate. Retrieved August 2, 2021, fromhttps://www.uptodate.com/contents/gestational-diabetes-mellitus-glycemic-control-and-maternal-prognosis
4. Insulin Regular Drug Information (n.d.). Uptodate. Retrieved August 3, 2021, fromhttps://www.uptodate.com/contents/insulin-regular-drug-information
5. Insulin glargine (n.d.). Medscape. Retrieved July 28, 2021, fromhttps://reference.medscape.com/drug/lantus-toujeo-insulin-glargine-999003#4
6. Types of Insulin (n.d.). UCSF Diabetes Education Online. Retrieved August 2, 2021, fromhttps://dtc.ucsf.edu/types-of-diabetes/type2/treatment-of-type-2-diabetes/medications-and-therapies/type-2-insulin-rx/types-of-insulin/#intacting
7. American Diabetes Association (2020). Management of diabetes in pregnancy. Standards of Medical Care in Diabetes. 43(1): S183–S192. Retrieved August 22, 2021, fromhttps://care.diabetesjournals.org/content/43/Supplement_1/S183
8. Brutsaert, E. F. (2020). Drug treatment of diabetes mellitus. MSD Manual Professional Version. Retrieved August 22, 2021, fromhttps://www.msdmanuals.com/professional/endocrine-and-metabolic-disorders/diabetes-mellitus-and-disorders-of-carbohydrate-metabolism/drug-treatment-of-diabetes-mellitus
9. Nolte Kennedy, M. S. (2012). Pancreatic hormones and antidiabetic drugs. In Katzung, B. G., Masters, S. B., & Trevor, A. J. (Eds.), Basic & Clinical Pharmacology (12th ed., pp. 743–765). Retrieved August 22, 2021, fromhttps://pharmacomedicale.org/images/cnpm/CNPM_2016/katzung-pharmacology.pdf