Non-insulinotropic Diabetes Drugs

Overview

Diabetes Diabetes Diabetes 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, type 2

• Caused by:
  • Peripheral insulin resistance Insulin resistance Diminished 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: cell insulin Insulin Insulin is a peptide hormone that is produced by the beta cells of the pancreas. Insulin plays a role in metabolic functions such as glucose uptake, glycolysis, glycogenesis, lipogenesis, and protein synthesis. Exogenous insulin may be needed for individuals with diabetes mellitus, in whom there is a deficiency in endogenous insulin or increased insulin resistance. Insulin receptors Receptors Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors do not respond appropriately to insulin Insulin Insulin is a peptide hormone that is produced by the beta cells of the pancreas. Insulin plays a role in metabolic functions such as glucose uptake, glycolysis, glycogenesis, lipogenesis, and protein synthesis. Exogenous insulin may be needed for individuals with diabetes mellitus, in whom there is a deficiency in endogenous insulin or increased insulin resistance. Insulin
  • Beta-cell dysfunction: long-term ↑ in insulin Insulin Insulin is a peptide hormone that is produced by the beta cells of the pancreas. Insulin plays a role in metabolic functions such as glucose uptake, glycolysis, glycogenesis, lipogenesis, and protein synthesis. Exogenous insulin may be needed for individuals with diabetes mellitus, in whom there is a deficiency in endogenous insulin or increased insulin resistance. Insulin demand → defective insulin Insulin Insulin is a peptide hormone that is produced by the beta cells of the pancreas. Insulin plays a role in metabolic functions such as glucose uptake, glycolysis, glycogenesis, lipogenesis, and protein synthesis. Exogenous insulin may be needed for individuals with diabetes mellitus, in whom there is a deficiency in endogenous insulin or increased insulin resistance. Insulin secretion Secretion Coagulation Studies
• Results in hyperglycemia Hyperglycemia Abnormally high blood glucose level. Diabetes Mellitus
• Pharmacologic management can target:
  • Insulin Insulin Insulin is a peptide hormone that is produced by the beta cells of the pancreas. Insulin plays a role in metabolic functions such as glucose uptake, glycolysis, glycogenesis, lipogenesis, and protein synthesis. Exogenous insulin may be needed for individuals with diabetes mellitus, in whom there is a deficiency in endogenous insulin or increased insulin resistance. Insulin release
  • Insulin resistance Insulin resistance Diminished 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
  • Glucagon Glucagon A 29-amino acid pancreatic peptide derived from proglucagon which is also the precursor of intestinal glucagon-like peptides. Glucagon is secreted by pancreatic alpha cells and plays an important role in regulation of blood glucose concentration, ketone metabolism, and several other biochemical and physiological processes. Gastrointestinal Secretions release
  • Gluconeogenesis Gluconeogenesis Gluconeogenesis 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
  • Glucose Glucose A 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

Classification

Hyperglycemic medications can be classified on the basis of their mechanism of action: 

Insulinotropic drugs: ↑ insulin Insulin Insulin is a peptide hormone that is produced by the beta cells of the pancreas. Insulin plays a role in metabolic functions such as glucose uptake, glycolysis, glycogenesis, lipogenesis, and protein synthesis. Exogenous insulin may be needed for individuals with diabetes mellitus, in whom there is a deficiency in endogenous insulin or increased insulin resistance. Insulin secretion Secretion Coagulation Studies

• Sulfonylureas Sulfonylureas Sulfonamides and Trimethoprim
• Meglitinides
• Glucagon-like peptide-1 ( GLP-1 GLP-1 A peptide of 36 or 37 amino acids that is derived from proglucagon and mainly produced by the intestinal l cells. Glp-1(1-37 or 1-36) is further n-terminally truncated resulting in glp-1(7-37) or glp-1-(7-36) which can be amidated. These glp-1 peptides are known to enhance glucose-dependent insulin release, suppress glucagon release and gastric emptying, lower blood glucose, and reduce food intake. Insulinomas) analogs
• DPP-4 inhibitors

Non-insulinotropic drugs: do not affect insulin Insulin Insulin is a peptide hormone that is produced by the beta cells of the pancreas. Insulin plays a role in metabolic functions such as glucose uptake, glycolysis, glycogenesis, lipogenesis, and protein synthesis. Exogenous insulin may be needed for individuals with diabetes mellitus, in whom there is a deficiency in endogenous insulin or increased insulin resistance. Insulin release 

• ↓ Insulin resistance Insulin resistance Diminished 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:
  • Biguanides
  • Thiazolidinediones (TZDs)
• ↓ Glucose Glucose A 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 absorption Absorption Absorption 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/reabsorption:
  • Alpha-glucosidase inhibitors
  • Sodium Sodium A member of the alkali group of metals. It has the atomic symbol na, atomic number 11, and atomic weight 23. Hyponatremia– glucose Glucose A 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 transport protein 2 (SGLT2) inhibitors
• ↓ Gastric emptying Gastric emptying The evacuation of food from the stomach into the duodenum. Gastrointestinal Motility and glucagon Glucagon A 29-amino acid pancreatic peptide derived from proglucagon which is also the precursor of intestinal glucagon-like peptides. Glucagon is secreted by pancreatic alpha cells and plays an important role in regulation of blood glucose concentration, ketone metabolism, and several other biochemical and physiological processes. Gastrointestinal Secretions secretion Secretion Coagulation Studies: amylin analogs

Biguanides

Metformin is the only available medication in the biguanide drug class.

Pharmacodynamics Pharmacodynamics Pharmacodynamics is the science that studies the biochemical and physiologic effects of a drug and its organ-specific mechanism of action, including effects on the cellular level. Pharmacokinetics is “what the body does to the drug,” whereas pharmacodynamics is “what the drug does to the body.” Pharmacokinetics and Pharmacodynamics

• The mechanism of action for metformin is not well understood, but it appears to help in the management of type 2 diabetes Diabetes Diabetes 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 by:
  • ↓ Gluconeogenesis Gluconeogenesis Gluconeogenesis 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 in:
    • Liver Liver The 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
    • Kidneys Kidneys The 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
  • ↓ GI glucose Glucose A 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 absorption Absorption Absorption 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
  • ↓ Insulin resistance Insulin resistance Diminished 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
  • ↑ Uptake of glucose Glucose A 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 by:
    • Muscle
    • Adipose tissue Adipose tissue Adipose 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
• Physiologic effect:
  • ↓ Fasting and postprandial glucose Glucose A 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
  • Weight stabilization or reduction
  • ↓ LDL 
  • ↑ HDL

Pharmacokinetics Pharmacokinetics Pharmacokinetics 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

• Absorption Absorption Absorption 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: oral
• Distribution:
  • Concentrates in:
    • Liver Liver The 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
    • Kidneys Kidneys The 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
    • GI tract
  • Negligible protein binding
• Excretion: by the kidneys Kidneys The 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 (unmetabolized)

Indications

• Type 2 diabetes Diabetes Diabetes 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:
  • Drug of choice for most cases
  • Well tolerated
  • Low cost 
  • No risk of hypoglycemia Hypoglycemia Hypoglycemia 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 with monotherapy
• Polycystic ovary syndrome (no longer 1st-line treatment)

Adverse effects

• GI effects (improves with dose reduction or discontinuation):
  • Metallic taste
  • Diarrhea Diarrhea Diarrhea is defined as ≥ 3 watery or loose stools in a 24-hour period. There are a multitude of etiologies, which can be classified based on the underlying mechanism of disease. The duration of symptoms (acute or chronic) and characteristics of the stools (e.g., watery, bloody, steatorrheic, mucoid) can help guide further diagnostic evaluation. Diarrhea 
  • Anorexia Anorexia The lack or loss of appetite accompanied by an aversion to food and the inability to eat. It is the defining characteristic of the disorder anorexia nervosa. Anorexia Nervosa 
  • Nausea Nausea An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. Antiemetics and vomiting Vomiting The forcible expulsion of the contents of the stomach through the mouth. Hypokalemia
• Lactic acidosis Lactic Acidosis Oxazolidinones:
  • Rare
  • Common in individuals with concurrent renal and hepatic disease
  • Due to impairment of lactic acid metabolism in hepatocytes Hepatocytes The main structural component of the liver. They are specialized epithelial cells that are organized into interconnected plates called lobules. Liver: Anatomy → released in bloodstream
• Vitamin B₁₂ deficiency
  • Occurs during long-term therapy 
  • Due to ↓ GI absorption Absorption Absorption 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 of vitamin B₁₂
  • Rarely results in megaloblastic anemia Megaloblastic anemia Megaloblastic anemia is a subset of macrocytic anemias that arises because of impaired nucleic acid synthesis in erythroid precursors. This impairment leads to ineffective RBC production and intramedullary hemolysis that is characterized by large cells with arrested nuclear maturation. The most common causes are vitamin B12 and folic acid deficiencies. Megaloblastic Anemia

Contraindications Contraindications A 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

• Severe renal disease
• History of lactic acidosis Lactic Acidosis Oxazolidinones
• Severe hepatic dysfunction
• Diabetic ketoacidosis Ketoacidosis A 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
• Avoid use:
  • Surgery
  • Iodinated contrast agents Contrast agents Substances used to allow enhanced visualization of tissues. Computed Tomography (CT) 
  • Hypoperfusion states
  • Excessive alcohol intake

Drug interactions

Drugs associated with increased metformin toxicity Toxicity Dosage Calculation:

• Ethanol Ethanol A clear, colorless liquid rapidly absorbed from the gastrointestinal tract and distributed throughout the body. It has bactericidal activity and is used often as a topical disinfectant. It is widely used as a solvent and preservative in pharmaceutical preparations as well as serving as the primary ingredient in alcoholic beverages. Ethanol Metabolism
• Iodinated contrast agents Contrast agents Substances used to allow enhanced visualization of tissues. Computed Tomography (CT)
• Topiramate Topiramate A sulfamate-substituted fructose analog that was originally identified as a hypoglycemic agent. It is used for the treatment of epilepsy and migraine disorders, and may also promote weight loss. Second-Generation Anticonvulsant Drugs

Thiazolidinediones

Medications in this class

• Pioglitazone
• Rosiglitazone

Pharmacodynamics Pharmacodynamics Pharmacodynamics is the science that studies the biochemical and physiologic effects of a drug and its organ-specific mechanism of action, including effects on the cellular level. Pharmacokinetics is “what the body does to the drug,” whereas pharmacodynamics is “what the drug does to the body.” Pharmacokinetics and Pharmacodynamics

• Work on:
  • Muscle
  • Adipose tissue Adipose tissue Adipose 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
• Ligands of peroxisome proliferator–activated receptors Receptors Receptors are proteins located either on the surface of or within a cell that can bind to signaling molecules known as ligands (e.g., hormones) and cause some type of response within the cell. Receptors (PPARs)
• Activation of PPARs → ↑ transcription Transcription Transcription of genetic information is the first step in gene expression. Transcription is the process by which DNA is used as a template to make mRNA. This process is divided into 3 stages: initiation, elongation, and termination. Stages of Transcription of genes Genes A category of nucleic acid sequences that function as units of heredity and which code for the basic instructions for the development, reproduction, and maintenance of organisms. DNA Types and Structure involved in:
  • Lipid and glucose Glucose A 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 metabolism
  • Insulin Insulin Insulin is a peptide hormone that is produced by the beta cells of the pancreas. Insulin plays a role in metabolic functions such as glucose uptake, glycolysis, glycogenesis, lipogenesis, and protein synthesis. Exogenous insulin may be needed for individuals with diabetes mellitus, in whom there is a deficiency in endogenous insulin or increased insulin resistance. Insulin signal transduction Transduction The transfer of bacterial DNA by phages from an infected bacterium to another bacterium. This also refers to the transfer of genes into eukaryotic cells by viruses. This naturally occurring process is routinely employed as a gene transfer technique. Bacteriology
  • Adipocyte Adipocyte Cells 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. Lipoma and other tissue differentiation
• ↑ Insulin Insulin Insulin is a peptide hormone that is produced by the beta cells of the pancreas. Insulin plays a role in metabolic functions such as glucose uptake, glycolysis, glycogenesis, lipogenesis, and protein synthesis. Exogenous insulin may be needed for individuals with diabetes mellitus, in whom there is a deficiency in endogenous insulin or increased insulin resistance. Insulin sensitivity → ↑ glucose Glucose A 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 and utilization

Pharmacokinetics Pharmacokinetics Pharmacokinetics 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

• Absorption Absorption Absorption 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:
  • Well absorbed orally
  • Delayed onset of action
• Distribution: highly protein-bound
• Metabolism:
  • Extensive hepatic metabolism
  • Cytochrome P450 Cytochrome P450 A superfamily of hundreds of closely related hemeproteins found throughout the phylogenetic spectrum, from animals, plants, fungi, to bacteria. They include numerous complex monooxygenases (mixed function oxygenases). In animals, these p450 enzymes serve two major functions: (1) biosynthesis of steroids, fatty acids, and bile acids; (2) metabolism of endogenous and a wide variety of exogenous substrates, such as toxins and drugs (biotransformation). They are classified, according to their sequence similarities rather than functions, into cyp gene families (>40% homology) and subfamilies (>59% homology). For example, enzymes from the cyp1, cyp2, and cyp3 gene families are responsible for most drug metabolism. Drug-Induced Liver Injury system
  • Pioglitazone has active metabolites.
• Excretion:
  • Pioglitazone: mostly in feces
  • Rosiglitazone: mostly in urine

Indications

TZDs are used for the treatment of type 2 diabetes Diabetes Diabetes 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:

• Not generally used in initial therapy
• More often used as 2nd- or 3rd-line therapy
• Can be combined with other agents
• Pioglitazone is useful in individuals with concurrent nonalcoholic steatohepatitis Nonalcoholic Steatohepatitis Nonalcoholic Fatty Liver Disease (NASH).

Adverse effects

• Weight gain:
  • Adipocyte Adipocyte Cells 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. Lipoma proliferation
  • Fluid retention
• ↑ Risk of congestive heart failure Heart Failure A heterogeneous condition in which the heart is unable to pump out sufficient blood to meet the metabolic need of the body. Heart failure can be caused by structural defects, functional abnormalities (ventricular dysfunction), or a sudden overload beyond its capacity. Chronic heart failure is more common than acute heart failure which results from sudden insult to cardiac function, such as myocardial infarction. Total Anomalous Pulmonary Venous Return (TAPVR) and cardiovascular events (especially with rosiglitazone)
• Bone Bone Bone is a compact type of hardened connective tissue composed of bone cells, membranes, an extracellular mineralized matrix, and central bone marrow. The 2 primary types of bone are compact and spongy. Bones: Structure and Types demineralization and ↑ fragility (increasing risk for bone fractures Bone fractures Breaks in bones. Bones: Remodeling and Healing) 
• Hepatotoxicity Hepatotoxicity Acetaminophen
• Possible ↑ bladder Bladder A musculomembranous sac along the urinary tract. Urine flows from the kidneys into the bladder via the ureters, and is held there until urination. Pyelonephritis and Perinephric Abscess cancer risk (pioglitazone)

Contraindications Contraindications A 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

• Class III or IV congestive heart failure Heart Failure A heterogeneous condition in which the heart is unable to pump out sufficient blood to meet the metabolic need of the body. Heart failure can be caused by structural defects, functional abnormalities (ventricular dysfunction), or a sudden overload beyond its capacity. Chronic heart failure is more common than acute heart failure which results from sudden insult to cardiac function, such as myocardial infarction. Total Anomalous Pulmonary Venous Return (TAPVR)
• Liver failure Liver failure Severe inability of the liver to perform its normal metabolic functions, as evidenced by severe jaundice and abnormal serum levels of ammonia; bilirubin; alkaline phosphatase; aspartate aminotransferase; lactate dehydrogenases; and albumin/globulin ratio. Autoimmune Hepatitis
• Pregnancy Pregnancy The status during which female mammals carry their developing young (embryos or fetuses) in utero before birth, beginning from fertilization to birth. Pregnancy: Diagnosis, Physiology, and Care
• Type 1 Type 1 Spinal Muscular Atrophy diabetes Diabetes Diabetes 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
• Bladder Bladder A musculomembranous sac along the urinary tract. Urine flows from the kidneys into the bladder via the ureters, and is held there until urination. Pyelonephritis and Perinephric Abscess cancer (active or prior history)
• Macular edema Edema Edema 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

Drug interactions

• ↑ Hypoglycemic effect:
  • Other antidiabetic medications
  • Androgens Androgens Androgens 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
  • Direct-acting antiviral agents Direct-Acting Antiviral Agents Antivirals for Hepatitis C
  • Antidepressants
• Fluid retention:
  • Pregabalin Pregabalin A gamma-aminobutyric acid (gaba) derivative that functions as a calcium channel blocker and is used as an anticonvulsant as well as an anti-anxiety agent. It is also used as an analgesic in the treatment of neuropathic pain and fibromyalgia. Second-Generation Anticonvulsant Drugs
  • Insulin Insulin Insulin is a peptide hormone that is produced by the beta cells of the pancreas. Insulin plays a role in metabolic functions such as glucose uptake, glycolysis, glycogenesis, lipogenesis, and protein synthesis. Exogenous insulin may be needed for individuals with diabetes mellitus, in whom there is a deficiency in endogenous insulin or increased insulin resistance. Insulin
• ↑ Risk of ischemic events:
  • Vasodilators Vasodilators Drugs used to cause dilation of the blood vessels. Thromboangiitis Obliterans (Buerger’s Disease)
  • Insulin Insulin Insulin is a peptide hormone that is produced by the beta cells of the pancreas. Insulin plays a role in metabolic functions such as glucose uptake, glycolysis, glycogenesis, lipogenesis, and protein synthesis. Exogenous insulin may be needed for individuals with diabetes mellitus, in whom there is a deficiency in endogenous insulin or increased insulin resistance. Insulin

Alpha-Glucosidase Inhibitors

Medications in this class

• Acarbose 
• Miglitol

Pharmacodynamics Pharmacodynamics Pharmacodynamics is the science that studies the biochemical and physiologic effects of a drug and its organ-specific mechanism of action, including effects on the cellular level. Pharmacokinetics is “what the body does to the drug,” whereas pharmacodynamics is “what the drug does to the body.” Pharmacokinetics and Pharmacodynamics

• Alpha glucosidases Alpha glucosidases Enzymes that catalyze the exohydrolysis of 1, 4-alpha-glycosidic linkages with release of alpha-glucose. Glycogen Metabolism:
  • Intestinal brush border enzymes Brush border enzymes Digestion and Absorption 
  • Convert carbohydrates Carbohydrates A class of organic compounds composed of carbon, hydrogen, and oxygen in a ratio of cn(H2O)n. The largest class of organic compounds, including starch; glycogen; cellulose; polysaccharides; and simple monosaccharides. Basics of Carbohydrates → monosaccharides Monosaccharides Single chain carbohydrates that are the most basic units of carbohydrates. They are typically colorless crystalline substances with a sweet taste and have the same general formula CNH2NON. Basics of Carbohydrates 
  • Only monosaccharides Monosaccharides Single chain carbohydrates that are the most basic units of carbohydrates. They are typically colorless crystalline substances with a sweet taste and have the same general formula CNH2NON. Basics of Carbohydrates can be transported from the gut lumen → bloodstream
• Competitive inhibition Competitive inhibition Enzyme Inhibition → ↓ carbohydrate digestion Digestion Digestion refers to the process of the mechanical and chemical breakdown of food into smaller particles, which can then be absorbed and utilized by the body. Digestion and Absorption in the proximal small intestine Small intestine The small intestine is the longest part of the GI tract, extending from the pyloric orifice of the stomach to the ileocecal junction. The small intestine is the major organ responsible for chemical digestion and absorption of nutrients. It is divided into 3 segments: the duodenum, the jejunum, and the ileum. Small Intestine: Anatomy → deferred to distal small intestine Small intestine The small intestine is the longest part of the GI tract, extending from the pyloric orifice of the stomach to the ileocecal junction. The small intestine is the major organ responsible for chemical digestion and absorption of nutrients. It is divided into 3 segments: the duodenum, the jejunum, and the ileum. Small Intestine: Anatomy
• Results in slowed glucose Glucose A 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 absorption Absorption Absorption 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 → ↓ post-meal glycemic excursion

Pharmacokinetics Pharmacokinetics Pharmacokinetics 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

• Absorption Absorption Absorption 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:
  • Acarbose: most is not absorbed
  • Miglitol: completely absorbed
• Metabolism:
  • Acarbose: degraded in the intestine by bacteria Bacteria Bacteria are prokaryotic single-celled microorganisms that are metabolically active and divide by binary fission. Some of these organisms play a significant role in the pathogenesis of diseases. Bacteriology and digestive enzymes Enzymes Enzymes are complex protein biocatalysts that accelerate chemical reactions without being consumed by them. Due to the body’s constant metabolic needs, the absence of enzymes would make life unsustainable, as reactions would occur too slowly without these molecules. Basics of Enzymes
  • Miglitol: none
• Excretion:
  • Acarbose: mostly in feces
  • Miglitol: mostly in urine

Indications

Alpha-glucosidase inhibitors are used to treat type 2 diabetes Diabetes Diabetes 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 as either:

• Monotherapy (generally not 1st-line)
• Adjunctive therapy

Adverse effects

• GI discomfort (due to fermentation of undigested carbohydrates Carbohydrates A class of organic compounds composed of carbon, hydrogen, and oxygen in a ratio of cn(H2O)n. The largest class of organic compounds, including starch; glycogen; cellulose; polysaccharides; and simple monosaccharides. Basics of Carbohydrates in the colon Colon The large intestines constitute the last portion of the digestive system. The large intestine consists of the cecum, appendix, colon (with ascending, transverse, descending, and sigmoid segments), rectum, and anal canal. The primary function of the colon is to remove water and compact the stool prior to expulsion from the body via the rectum and anal canal. Colon, Cecum, and Appendix: Anatomy):
  • Flatulence
  • Bloating Bloating Constipation
  • Diarrhea Diarrhea Diarrhea is defined as ≥ 3 watery or loose stools in a 24-hour period. There are a multitude of etiologies, which can be classified based on the underlying mechanism of disease. The duration of symptoms (acute or chronic) and characteristics of the stools (e.g., watery, bloody, steatorrheic, mucoid) can help guide further diagnostic evaluation. Diarrhea
  • Abdominal pain Abdominal Pain Acute Abdomen
• ↑ Liver Liver The 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 enzymes Enzymes Enzymes are complex protein biocatalysts that accelerate chemical reactions without being consumed by them. Due to the body’s constant metabolic needs, the absence of enzymes would make life unsustainable, as reactions would occur too slowly without these molecules. Basics of Enzymes

Contraindications Contraindications A 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

• Renal impairment
• Hepatic impairment
• GI motility GI Motility The primary functions of the GI tract are digestion and absorption, which require coordinated contractions of the smooth muscles present in the GI tract. Peristaltic waves, segmentation contractions, and the migrating motor complex are all important contraction patterns that help to mix contents, get them in contact with the intestinal walls, and propel material down the tract at appropriate times and in appropriate amounts. Gastrointestinal Motility disease
• Predisposition to bowel obstruction Bowel obstruction Any impairment, arrest, or reversal of the normal flow of intestinal contents toward the anal canal. Ascaris/Ascariasis
• Inflammatory bowel disease

Sodium–glucose transport protein 2 (SGLT2) Inhibitors

Medications in this class

• Dapagliflozin
• Empagliflozin 
• Canagliflozin 
• Ertugliflozin

Pharmacodynamics Pharmacodynamics Pharmacodynamics is the science that studies the biochemical and physiologic effects of a drug and its organ-specific mechanism of action, including effects on the cellular level. Pharmacokinetics is “what the body does to the drug,” whereas pharmacodynamics is “what the drug does to the body.” Pharmacokinetics and Pharmacodynamics

• SGLT2:
  • Located in the proximal tubule Proximal tubule The renal tubule portion that extends from the bowman capsule in the kidney cortex into the kidney medulla. The proximal tubule consists of a convoluted proximal segment in the cortex, and a distal straight segment descending into the medulla where it forms the u-shaped loop of henle. Tubular System 
  • Responsible for glucose Glucose A 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 reabsorption
• Inhibition of SGLT2 → ↓ reabsorption of filtered glucose Glucose A 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
• Result: ↑ urinary glucose Glucose A 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 excretion and ↓ blood glucose Glucose A 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 level

Pharmacokinetics Pharmacokinetics Pharmacokinetics 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

• Absorption Absorption Absorption 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: rapid oral absorption Absorption Absorption 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
• Distribution: protein-bound
• Metabolism:
  • Hepatic
  • Glucuronidation
  • Minimal cytochrome P450 Cytochrome P450 A superfamily of hundreds of closely related hemeproteins found throughout the phylogenetic spectrum, from animals, plants, fungi, to bacteria. They include numerous complex monooxygenases (mixed function oxygenases). In animals, these p450 enzymes serve two major functions: (1) biosynthesis of steroids, fatty acids, and bile acids; (2) metabolism of endogenous and a wide variety of exogenous substrates, such as toxins and drugs (biotransformation). They are classified, according to their sequence similarities rather than functions, into cyp gene families (>40% homology) and subfamilies (>59% homology). For example, enzymes from the cyp1, cyp2, and cyp3 gene families are responsible for most drug metabolism. Drug-Induced Liver Injury–mediated metabolism
• Excretion: in urine and feces

Indications

Sodium Sodium A member of the alkali group of metals. It has the atomic symbol na, atomic number 11, and atomic weight 23. Hyponatremia– glucose Glucose A 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 transport protein 2 inhibitors are used for the treatment of type 2 diabetes Diabetes Diabetes 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:

• Adjunctive therapy
• Not typically used as initial therapy
• Help with weight loss Weight loss Decrease in existing body weight. Bariatric Surgery
• Potential morbidity Morbidity The proportion of patients with a particular disease during a given year per given unit of population. Measures of Health Status and mortality Mortality All deaths reported in a given population. Measures of Health Status benefit for individuals with cardiovascular and renal comorbidities Comorbidities The presence of co-existing or additional diseases with reference to an initial diagnosis or with reference to the index condition that is the subject of study. Comorbidity may affect the ability of affected individuals to function and also their survival; it may be used as a prognostic indicator for length of hospital stay, cost factors, and outcome or survival. St. Louis Encephalitis Virus (e.g., diabetic nephropathy Diabetic nephropathy Kidney injuries associated with diabetes mellitus and affecting kidney glomerulus; arterioles; kidney tubules; and the interstitium. Clinical signs include persistent proteinuria, from microalbuminuria progressing to albuminuria of greater than 300 mg/24 h, leading to reduced glomerular filtration rate and end-stage renal disease. Chronic Diabetic Complications)

Additional indications:

• Chronic kidney disease Chronic Kidney Disease Chronic kidney disease (CKD) is kidney impairment that lasts for ≥ 3 months, implying that it is irreversible. Hypertension and diabetes are the most common causes; however, there are a multitude of other etiologies. In the early to moderate stages, CKD is usually asymptomatic and is primarily diagnosed by laboratory abnormalities. Chronic Kidney Disease with proteinuria Proteinuria The presence of proteins in the urine, an indicator of kidney diseases. Nephrotic Syndrome in Children → slows renal function decline and reduces proteinuria Proteinuria The presence of proteins in the urine, an indicator of kidney diseases. Nephrotic Syndrome in Children
• Heart failure Heart Failure A heterogeneous condition in which the heart is unable to pump out sufficient blood to meet the metabolic need of the body. Heart failure can be caused by structural defects, functional abnormalities (ventricular dysfunction), or a sudden overload beyond its capacity. Chronic heart failure is more common than acute heart failure which results from sudden insult to cardiac function, such as myocardial infarction. Total Anomalous Pulmonary Venous Return (TAPVR) → reduces mortality Mortality All deaths reported in a given population. Measures of Health Status and hospitalizations

Adverse effects

• Glucosuria Glucosuria Diabetes Mellitus → ↑ risk of genitourinary tract infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease
• Osmotic diuresis Osmotic diuresis Volume Depletion and Dehydration leads to:
  • Polyuria Polyuria Urination of a large volume of urine with an increase in urinary frequency, commonly seen in diabetes. Renal Potassium Regulation
  • Hypovolemia Hypovolemia Sepsis in Children
  • Hypotension Hypotension Hypotension is defined as low blood pressure, specifically < 90/60 mm Hg, and is most commonly a physiologic response. Hypotension may be mild, serious, or life threatening, depending on the cause. Hypotension
  • AKI AKI Acute kidney injury refers to sudden and often reversible loss of renal function, which develops over days or weeks. Azotemia refers to elevated levels of nitrogen-containing substances in the blood that accompany AKI, which include BUN and creatinine. Acute Kidney Injury
• ↑ Risk of fractures
• ↑ Risk of diabetic ketoacidosis Ketoacidosis A 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
• Hypersensitivity reactions
• Lower limb amputations (specifically canagliflozin)

Contraindications Contraindications A 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

• Severe renal impairment (less effective)
• Frequent urinary tract Urinary tract The urinary tract is located in the abdomen and pelvis and consists of the kidneys, ureters, urinary bladder, and urethra. The structures permit the excretion of urine from the body. Urine flows from the kidneys through the ureters to the urinary bladder and out through the urethra. Urinary Tract: Anatomy infections Infections Invasion of the host organism by microorganisms or their toxins or by parasites that can cause pathological conditions or diseases. Chronic Granulomatous Disease
• Type 1 Type 1 Spinal Muscular Atrophy diabetes Diabetes Diabetes 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
• Diabetic ketoacidosis Ketoacidosis A 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

Amylin Analogs

Pramlintide is the only medication in the amylin analog class.

Pharmacodynamics Pharmacodynamics Pharmacodynamics is the science that studies the biochemical and physiologic effects of a drug and its organ-specific mechanism of action, including effects on the cellular level. Pharmacokinetics is “what the body does to the drug,” whereas pharmacodynamics is “what the drug does to the body.” Pharmacokinetics and Pharmacodynamics

• Amylin is usually cosecreted with insulin Insulin Insulin is a peptide hormone that is produced by the beta cells of the pancreas. Insulin plays a role in metabolic functions such as glucose uptake, glycolysis, glycogenesis, lipogenesis, and protein synthesis. Exogenous insulin may be needed for individuals with diabetes mellitus, in whom there is a deficiency in endogenous insulin or increased insulin resistance. Insulin by beta cells in the pancreas Pancreas The 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.
• This secretion Secretion Coagulation Studies is deficient in type 1 Type 1 Spinal Muscular Atrophy diabetes Diabetes Diabetes 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 and relatively deficient in type 2 diabetes Diabetes Diabetes 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.
• Analogs help with glucose Glucose A 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 by:
  • Slowing gastric emptying Gastric emptying The evacuation of food from the stomach into the duodenum. Gastrointestinal Motility and ↑ satiety → ↓ food intake
  • ↓ Postprandial glucagon Glucagon A 29-amino acid pancreatic peptide derived from proglucagon which is also the precursor of intestinal glucagon-like peptides. Glucagon is secreted by pancreatic alpha cells and plays an important role in regulation of blood glucose concentration, ketone metabolism, and several other biochemical and physiological processes. Gastrointestinal Secretions secretion Secretion Coagulation Studies

Pharmacokinetics Pharmacokinetics Pharmacokinetics 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

• Absorption Absorption Absorption 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: given as a subcutaneous injection (must be injected in a site different from the site used for insulin Insulin Insulin is a peptide hormone that is produced by the beta cells of the pancreas. Insulin plays a role in metabolic functions such as glucose uptake, glycolysis, glycogenesis, lipogenesis, and protein synthesis. Exogenous insulin may be needed for individuals with diabetes mellitus, in whom there is a deficiency in endogenous insulin or increased insulin resistance. Insulin injection)
• Metabolism:
  • Renal
  • Active metabolite
• Excretion: in urine

Indications

• Used in types 1 and 2 diabetes Diabetes Diabetes 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
• Individuals should be on prandial insulin Insulin Insulin is a peptide hormone that is produced by the beta cells of the pancreas. Insulin plays a role in metabolic functions such as glucose uptake, glycolysis, glycogenesis, lipogenesis, and protein synthesis. Exogenous insulin may be needed for individuals with diabetes mellitus, in whom there is a deficiency in endogenous insulin or increased insulin resistance. Insulin.
• Administered immediately prior to meals

Adverse effects

• Nausea Nausea An unpleasant sensation in the stomach usually accompanied by the urge to vomit. Common causes are early pregnancy, sea and motion sickness, emotional stress, intense pain, food poisoning, and various enteroviruses. Antiemetics and vomiting Vomiting The forcible expulsion of the contents of the stomach through the mouth. Hypokalemia
• Anorexia Anorexia The lack or loss of appetite accompanied by an aversion to food and the inability to eat. It is the defining characteristic of the disorder anorexia nervosa. Anorexia Nervosa
• Hypoglycemia Hypoglycemia Hypoglycemia 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 (usually in type 1 Type 1 Spinal Muscular Atrophy diabetes Diabetes Diabetes 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)

Contraindications Contraindications A 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

• Gastroparesis Gastroparesis Chronic delayed gastric emptying. Gastroparesis may be caused by motor dysfunction or paralysis of stomach muscles or may be associated with other systemic diseases such as diabetes mellitus. Malabsorption and Maldigestion
• Hypoglycemia Hypoglycemia Hypoglycemia 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 unawareness
• Hypersensitivity to pramlintide

Drug interactions

• ↑ Hypoglycemic effect with other antidiabetic medications
• May delay absorption Absorption Absorption 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 of oral medications

Comparison of Antidiabetic Medications

The following table compares the different (noninsulin) type 2 diabetes Diabetes Diabetes 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 medications:

The effects of diabetes Diabetes Diabetes 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 medications on weight may be a factor in choosing therapy:

• Weight loss Weight loss Decrease in existing body weight. Bariatric Surgery:
  • GLP-1 GLP-1 A peptide of 36 or 37 amino acids that is derived from proglucagon and mainly produced by the intestinal l cells. Glp-1(1-37 or 1-36) is further n-terminally truncated resulting in glp-1(7-37) or glp-1-(7-36) which can be amidated. These glp-1 peptides are known to enhance glucose-dependent insulin release, suppress glucagon release and gastric emptying, lower blood glucose, and reduce food intake. Insulinomas mimetics
  • SGLT2 inhibitors
• Weight neutral:
  • α-glucosidase inhibitors
  • DPP-4 inhibitors
• Weight gain:
  • Insulin Insulin Insulin is a peptide hormone that is produced by the beta cells of the pancreas. Insulin plays a role in metabolic functions such as glucose uptake, glycolysis, glycogenesis, lipogenesis, and protein synthesis. Exogenous insulin may be needed for individuals with diabetes mellitus, in whom there is a deficiency in endogenous insulin or increased insulin resistance. Insulin
  • Sulfonylureas Sulfonylureas Sulfonamides and Trimethoprim
  • Thiazolidinediones
  • Meglitinides