DM pharmacology HS _student version 3 2023 (1).pptx

Diabetes Mellitus(DM) Pharmacology Harleen Singh Pharm D. Clinical Professor Diabetes Mellitus • Diabetes mellitus (DM), is a complex metabolic disorder characterized by hyperglycemia. • Hyperglycemia results from anomalies in either insulin secretion or insulin action or both Some Facts • 34.2...

Diabetes Mellitus(DM) Pharmacology Harleen Singh Pharm D. Clinical Professor Diabetes Mellitus • Diabetes mellitus (DM), is a complex metabolic disorder characterized by hyperglycemia. • Hyperglycemia results from anomalies in either insulin secretion or insulin action or both Some Facts • 34.2 million DM ( just over 1 in 10, or 13% of the U.S. population) • Prediabetes can be found in 88 million American adults • Prevalence of diabetes in 2019 is 9.3% and expected to rise to 10.2% by 2030 and 10.9% by 2045 • Type 2 diabetes can be delayed or prevented in patients with prediabetes Centers for Disease Control and Prevention. National Diabetes Statistics Report, 2020. Published February 11, 2020. Accessed Feb 14, 2023. https://www.cdc.gov/diabetes/library/features/diabetes-stat-report.html American Diabetes Association. 3. Prevention or delay of type 2 diabetes: Standards of Medical Care in Diabetes—2021. Diabetes Care. 2021;44(suppl 1):S34–S39. doi:10.2337/dc21-S003 Balance Lower blood glucose Raise Blood glucose Role of Hormones Role of Hormones GLP-1 (glucagon-like peptide-1) GIP (glucose-dependent insulinotropic polypeptide) Dipeptidyl peptidase 4 (DPP-4) inhibitors The Effect Of Amylin https://dtc.ucsf.edu/types-of-diabetes/type1/understanding-type-1-diabetes/how-the-body-processes-sugar/blood-sugar- The Effect of GLP-I and GIP GLP-1 (glucagon-like peptide-1) GIP (glucose-dependent insulinotropic polypeptide) https://dtc.ucsf.edu/types-of-diabetes/type1/understanding-type-1-diabetes/how-the-body-processes-sugar/blood-sugar-other-hormones/ Glucose Counter – Regulatory Hormones: Effect on Liver https://dtc.ucsf.edu/types-of-diabetes/type1/understanding-type-1-diabetes/how-the-body-processes-sugar/blood-sugar-other- Types of Diabetes Mellitus Banday MZ, Sameer AS, Nissar S. Pathophysiology of diabetes: An overview. Avicenna J Med 2020;10:174-88. Characteristics Type 1 Diabetes Mellitus Type 2 Diabetes Mellitus Other Names Previously. type: insulin-dependent diabetes mellitus (IDDM); juvenile-onset diabetes mellitus Previously, type I; non-insulin-dependent diabetes mellitus (NIDDM); adult-onset diabetes mellitus Percentage of diabetic population 5%-10% 90% Age of onset Usually <30 years; peaks at 12-14 years; rare before 6 months; some adults develop type 1 during the fifth decade. Usually >40 years, but increasing prevalence among obese children Pancreatic Function Usually none, although some residual Cpeptide can sometimes be detected at diagnosis, especially in adults Insulin present in low, "normal," or high amounts Pathogenesis Associated with certain HLA Types; presence of islet cell antibodies suggest autoimmune process Defect in insulin secretion; tissue resistance to insulin 1 hepatic glucose output Family History Generally not strong Strong Uncommon Common (60%-90%) Often present Rare Infection Obesity History of Ketoacidosis Clinical Presentation Moderate-to-severe symptoms that generally progress relatively rapidly (days to weeks): Mild polyuria, fatigue; often diagnosed on routine Management of Diabetes https://www.montgomerycountymd.gov/healthymontgomery/programs/type-2-diabetes/ Risk Factors for Type 2 DM Banday MZ, Sameer AS, Nissar S. Avicenna J Med 2020;10:174-88. Metabolic syndrome • Complications Microvascular (retinopathy, nephropathy, neuropathy) Macrovascular (peripheral vascular disease, CVD, stroke) IFG= impaired fasting glucose, IGT= impaired glucose tolerance. Zeind, Caroline, S. et al. Applied Therapeutics. Available from: VitalSource Bookshelf, (12th Edition). Wolters Diagnostic Criteria for Prediabetes and Diabetes Prediabetes Diabetes A1C 5.7-6.4% (39-47 mmol/mol)* ≥6.5% (48 mmol/mol)† FPG 100-125 mg/dL (5.6-6.9 mmol/L)* ≥126 mg/dL (7.0 mmol/L)† 2-hour plasma glucose during 75g OGTT 140-199 mg/dL (7.8-11.0 mmol/L)* ≥200 mg/dL (11.1 mmol/L)† Random plasma glucose — ≥200 mg/dL (11.1 mmol/L)‡ Adapted from Tables 2.2 and 2.5 in the complete 2023 Standards of Care. • For all three tests, risk is continuous, extending below the lower limit of the range and becoming disproportionately greater at the higher end of the range. † In the absence of unequivocal hyperglycemia, diagnosis requires two abnormal test results from the same sample or in two separate samples. ‡ Only diagnostic in a patient with classic symptoms of hyperglycemia or hyperglycemic crisis. IFG= impaired fasting glucose, IGT= impaired glucose tolerance, FPG=Fasting blood glucose, OGTT=oral glucose tolerance test Glycated Hemoglobin A1C (%) Estimated Average Plasma Glucose (mg/dL) 5 97 (76-120) 6 126 (100-152) 7 154 (123-185) 8 183 (147-217) 9 212 (170-249) 10 240 (193-282) 11 269 (217-314) 12 298 (240-347) A1c into an average glucose: 28.7 × A1c − 46.7 = eAG (estimated average glucose) (A1c − 2) × 30. Glycemic goals Glycemic Goals A1c <7.0 (normal, 4%-6%) Pre-prandial plasma glucose 80-130 mg/dL (4.4-7.2 mmol/L) Postprandial plasma glucose (2 hours) <180 mg/dL (<10.0 mmol/L) Source: American Diabetes Association. 6. Glycemic targets: Standards of Medical Care in Diabetes—2021. Diabetes Care. 2021;44(suppl 1):S73–S84. doi:10.2337/dc21-S006. Goals of Physiologic (Basal-Bolus) Insulin Therapy Motoring Parameter Adults (mg/dL) Pediatric- young adult (6-29 years) mg/dL Pregnancy (mg/dL) Premeal 80-130 mg/dL 90-130 mg/dL 60-99 mg/dL 2 Hr postprandial plasma glucose < 180 mg/dL Not routinely recommended 60-140mg/dL Bedtime/overnight (0200-0400 plasma glucose 80-150mg/dL 80-150 mg/dL 70-95 mg/dL A1C <7.0% <6.5-7.5 <6-7% Urine ketones Absent to rare Absent to rare Rare Pathogenesis of Type 1 Diabetes Zhong T, Tang R, Gong S, Li J, Li X, Zhou Z. The remission phase in type 1 diabetes: changing epidemiology, definitions, and emerging immunometabolic mechanisms. Diabetes Metab Res Rev. 2020;36(2). doi:10.1002/dmrr.3207 Symptoms of Type I DM • Fatigue/weight loss • Glucosuria • Polyuria • Polydipsia • Polyphagia • DKA Normal Glucose Brain Liver Muscle Mechanism of Insulin Insulin Secretion Glucose enters β-cells via GLUT2 ATP produced K+/ATP channel closes, Cell depolarizes Ca++ influx Insulin-containing vesicles fuse with the plasma membrane Modified from Golan DE. Principles of Pharmacology: The Pathophysiologic Basis of Therapeutics. 4th Endogenous insulin Bolus insulin Basal insulin Adapted from Leahy J, Cefalu W, eds. Insulin therapy. New York, NY: Marcel Dekkerinc;2002:87 Insulin (Grouped by onset of action) Ultra Long-acting • Insulin degludec (Tresiba) Long-acting • Insulin detemir (Levemir®) • Insulin glargine (Lantus®,Toujeo®,Basaglar®) • Insulin Degludec( Tresiba®) Intermediate-acting • Insulin NPH (Humulin®N Novolin® N) Short-acting • Regular insulin (Humulin® R) • Regular insulin (Novolin® R) Rapid-acting • Insulin glulisine (Apidra®) • Insulin aspart (NovoLog®) • Insulin lispro (Humalog®) Subtypes and approximate durations of action of different insulin formulations Adapted from Kennedy & Masharani (2015). Examples of physiologic insulin delivery https://tmedweb.tulane.edu/pharmwiki/doku.php/insulin_regimens Summary NPH/regular (70%/30%) Empiric Insulin Doses Type 1 diabetes Initial dose 0.3 – 0.5 units/kg Honeymoon phase 0.2 – 0.5 units/kg With ketosis, during illness, during growth 1.0 – 1.5 units/kg Type 2 Diabetes With insulin resistance 0.1 – 0.2 units/kg Factors Altering Onset and Duration of Insulin Action Site of injection Rate of absorption is fastest from the abdomen, intermediate from the arm, and slowest from the thigh. Less variation is observed in patients with type 2 diabetes; less variation is observed with current rapid-acting and long-acting insulins Site Half-life absorption (minutes) Abdomen 87 + 12 Arm 141 + 23 Hip 153 + 28 Thigh 164 + 15 Estimating Premeal Insulin Requirements Estimating Premeal Insulin Requirements The premeal insulin requirements are ~ 50% of the TDD, usually divided equally into three doses initially, taken with each meal (i.e. breakfast, lunch, and dinner), and then each premeal dose is individually adjusted base on BG readings. The ”500 rule” estimates the number of grams of carbohydrates that will be covered by 1 unit of rapid-acting insulin. The rule is modified to the “450 rule” if using regular insulin. 500/ TDD of insulin – number of grams covered Example: For a patient using 50 units/day, 500/50 =10. Therefore, 10 g of carbohydrates would be covered by 1 unit of insulin lispro, glulisine, or aspart. This equation works very well for patients with type 1 diabetes in estimating their premeal insulin requirements. Because patients with type 2 diabetes have insulin resistance, the rule may underestimate their insulin requirements. Zeind, Caroline, S. et al. Applied Therapeutics. Available from: VitalSource Bookshelf, (12th Edition). Wolters Determining the “Correction Factor” Premeal blood glucose target is 120 mg/dL Patient’s value is 190 mg/dL, additional units of rapidacting insulin could be added to the premeal dose. The correction factor determines how far the blood glucose drops per unit of insulin given and is known as the “1700 rule.” For regular insulin, the rule is modified to the “1500 rule.” The equation is:1700/TDD = point drop in blood glucose per unit of insulin Zeind, Caroline, S. et al. Applied Therapeutics. Available from: VitalSource Bookshelf, (12th Edition). Wolters Example If a patient uses 28 units/day of insulin, their correction factor (or insulin sensitivity) would be 1700/28 = 60 mg/dL. Therefore, the patient can expect a 60-mg/dL drop for every unit of rapid-acting insulin administered. • Patients with a higher sensitivity factor have lower insulin requirements. • Individuals with a lower sensitivity factor (higher insulin requirements) typically achieve a smaller reduction in blood glucose per unit of insulin Zeind, Caroline, S. et al. Applied Therapeutics. Available from: VitalSource Bookshelf, (12th Edition). Wolters Hypoglycemia Level 1 Blood glucose concentration <70 mg/dL, but ≥54 mg/dL: Patient may or may not be symptomatic (tremors, palpitations, sweating, intense hunger); patients are able to self-treat. Level 2 Blood glucose <54 mg/dL: Patient is generally symptomatic; patient may be neuroglycopenic (experience autonomic symptoms: headache, mood changes, decreased attention, drowsiness). Patients may require assistance in treating. Level 3 No designated blood glucose: Severe hypoglycemia associated with altered mental status and physical function; patient may become unconscious, unresponsive, or have convulsions. Patients require assistance for appropriate Zeind, Caroline, S. et al. Applied Therapeutics. Availabletreatment. from: VitalSource Bookshelf, (12th Edition). Wolters Common Signs and Symptoms of Hypoglycemia • Blurred vision, sweaty palms, generalized sweating, tremulousness, hunger, confusion, anxiety, circumoral tingling, and numbness. • Patients very regard to their symptoms. • Behavior can be confused with alcohol inebriation. Patients become combative and use poor judgment. • Nocturnal hypoglycemia: nightmares, restless sleep, profuse sweating, morning headache, morning “hangover”. • Not all patients have symptoms during nocturnal hypoglycemia. Treatment of Hypoglycemia Ingest 10-20 g of rapidly absorbed carbohydrate. Repeat in 15-20 minutes if glucose concentration remains <70 mg/dL or if patient is symptomatic. Follow with complex carbohydrate/protein snack if mealtime is not imminent. The following are examples of food sources that provide 15 g of carbohydrates: Orange, grapefruit, or apple juice; 1/2 cup regular, non-diet soda Fat-free milk 1 cup Grape juice, cranberry juice cocktail 1/3 cup If patient is unconscious, the following measures should be initiated: • Glucagon 1 mg intranasal, SC, IM, or IV (generally administered IM in outpatient setting; mean response time, 6.5 minutes) • Glucose 25 g IV (dextrose 50%, 50 mL; mean response time, 4 minutes) Amylin Analog • Amylin is a neuroendocrine hormone that is co-secreted with insulin following a meal. Complements the glucose-regulatory actions of insulin. • Type 1 diabetics lack endogenous amylin, and type 2 diabetics are relatively deficient in amylin • Pramlintide = stable analog of human amylin • MOA: suppresses glucagon release, slows gastric emptying, increases satiety • Modest weight loss • Subcutaneous injection • Given post-meals • ADRs: nausea, vomiting, anorexia • (Lipodystrophy from poor injection technique) Gestationa l Pregnancy and DM • Pregestational diabetes, • Gestational diabetes mellitus (GDM) Placental hormones (eg, human placental lactogen, progesterone, prolactin [PRL], placental growth hormone, and cortisol) are thought to be responsible for the increase in insulin resistance during pregnancy. • Goals of therapy: to reduce the maternal and fetal morbidity and mortality associated with diabetes Treatment Type •The use of lispro (Humalog®) and aspart (Novolog®) •Glargine and Neutral protamine Hagedorn (NPH) insulin •insulin detemir (Levemir®) and insulin glulisine (Apidra®) Dosing •Range from 0.7 to 0.8 units/kg/day in the first trimester. •24 weeks’ gestation begin to increase from 0.8 to 1 unit/kg/day •Third trimester from 0.9 to 1.2 units/kg/day Insulin secretion GI α-Glucosidase Inhibitors ↑Sulfonylureas ↑Glinides Incretins ↑Incretins Dipeptidyl Peptidase-4 Inhibitors Bile acid sequestrants Amylinomimetics Glucagon secretion ↓Incretins ↓Amylinomimetic s Hyperglycemia Hepatic glucose output ↓Metformin ↓Thiazolidinediones Appetite control Incretins Amylinomimeti cs Neurotransmitter dysfunction BROMOCRIPTINE Glucose reabsorption ↓Sodium–Glucose Transporte 2 Inhibitors Lipotoxicit y Thiazolidinedione Glucose uptake and utilization ↑Thiazolidinediones ↑Metformin Mechanism of Action of Metformin Biguanide MOA Generic Brand Decreases hepatic glucose production (gluconeogenesis) and intestinal absorption of glucose. While improving insulin sensitivity Metformin (Glucophage, Glucophage ER)   Dosing Advantages Contraindicati ons • • • • • • • • • 500 mg once daily 850 mg once daily 500 mg twice daily 1000 mg once daily 850 mg twice daily 1000 mg twice daily  Weight neutral or modest weight loss Lower A1c 1-1.5% Low risk of hypoglycemia • eGFR<30 ml/min • liver disease • severe infection • GI effects: B12 deficiencies Common side effects  Counselling Points Take with food to ↓ stomach upset GI symptoms improve with time - manage by slow dose titration Extended-release formulation has less GI issues Metallic tase • • • • Abdominal pain Flatulence Abdominal Cramping Diarrhea Possible Mechanism of Action of Sulfonylureas Sulfonylureas (SFU) and glinides both bind the SUR1 subunit Inhibit the β-cell K+/ATP channel Membrane depolarization and Ca2+ influx Fusion of insulin-containing vesicles with the plasma membrane Insulin secretion https://www.lecturio.com/concepts/insulinotropic-diabetes-medications/ Sulfonylureas MOA These drugs bind to ATP-sensitive potassium channels located on pancreatic beta cells. The closed potassium channel cause voltage-gated calcium channels to open leading to an influx of calcium ions. The influx of calcium causes increased insulin secretion. Secondary effects of these medications enhance insulin action, reduce hepatic glucose production and increase insulin sensitivity. ​ Generic (Glim-, Gly) Brand Dosing Advantages Contraindication s Common side effects Monitoring Glimepiride (Amaryl) • 1 to 2 mg once daily • 4 to 8 mg once daily Glipizide (Glucotrol) • 2.5 to 5 mg once daily. • 10 mg once daily • CrCl <50 ml/min avoid Glyburide (DiaBeta) • 1.25 to 5 mg once daily • 10 mg once daily Counselling Points  Take with food except for glipizide which is 30 minutes before meals  Recommend frequent glucose monitoring  Titrate slowly  Educate patients on symptoms of hypoglycemia  Lose effectiveness over time commonly 5 years • Rapid onset of action • Lower A1C(1%) • Affordability • Type 1 diabetes • Caution in renal and hepatic impairment • • • • Weight gain(5-10Ibs) Upset stomach (nausea/vomiting) Risk of hypoglycemia Hypersensitivity reaction (sulfa allergy) • POC Glucose • A1C • Kidney function Beers Criteria: DO NOT use in elderly Mechanism of Action of Glitazone Insulin sensitizers Pioglitazone also activates PPAR-α (peroxisome proliferator-activated receptor-γ [PPAR-γ]) https://tmedweb.tulane.edu/pharmwiki/doku.php/thiazolidinediones Thiazolidinediones MOA Generic (-glitazone) Brand Dosing Advantages Contraindications Common side effects Monitoring Bind to PPAR-gamma receptors in muscles, adipose tissue and the liver leading to an increase in insulin sensitivity and glucose uptake in muscle and adipose tissue which decreases glucose production in the liver Pioglitazone (Actos) • 15 to 30 mg once daily • 45 mg once daily Counselling points May take several weeks for effects to show May improve lipids Frequent daily glucose checks recommended Educate patients on symptoms of hypoglycemia • Positive lipid effects • Lower A1C (0.9%–1.3% decrease with a sulfonylurea, 0.8%–1.0% decrease with metformin, and 0.7%– 1.0% decrease with insulin) • No hypoglycemia • BBW: Exacerbating heart failure • NYHA class III/IV • Increased risk of fracture(female) • Active liver disease /bladder cancer • Weight gain (2–3 kg) interactions :Pioglitazone induces CYP3A4 • Peripheral edema/HF Pioglitazone is a substrate of CYP2C8 • Increase risk of bladder cancer • Increase risk of bone fracture • POC Glucose Drug Role of Incretins in Glucose Homeostasis Kieffer TJ, Habena JF EndocrRev 1990;20:876-913,Drucker DJ Diabetes Care 2003;26:2 929-2940, Holst JJ Diabetes Metab Res Rev. GLP-1 Receptor Agonist MOA Incretin mimetics that bind to and activate GLP-I receptors located in the pancreas ↑ insulin secretions, ↓ glucagon secretions, slowing gastric emptying . This causes promoting feeling of fullness which result in weight loss Generic (-tide) Brand Dosing Advantages Contraindicatio ns Common side effects Dulaglutide (Trulicty) • 0.75 mg weekly • 1.5 mg weekly • 3 mg weekly • 4.5 mg weekly Exenatide (Byetta) Exenatide ER (Bydureon) • 5 mcg Twice daily • 10 mcg Twice daily • 2 mg once weekly Liraglutide (Victoza) • 0.6 mg once daily • 1.2 mg once daily • 1.8 mg once daily Tirzepatide (Mounjaro) • 2.5 mg once weekly • 5 mg once weekly • 7.5 mg once weekly • 10 mg once weekly • 12.5 mg once weekly • 15 mg once weekly Semaglutide (Ozempic) • 0.25 mg once weekly • 0.5 mg once weekly Counselling points  SubQ injections are preferably administered in the stomach area once inch away from the belly button  Rotate injection site each time  GI symptoms typically resolve with time  Best to advised patient to keep injections in the refrigerator  Pregnancy Category X • Reduced appetite. • Weight loss[1.5–5 kg] • Lower A1c 0.8-1.6% • Low risk of hypoglycemia • Cardiovascular and/or renal benefits • Family hx of medullary thyroid carcinoma • eGFR <30 ml/min (Exentide) • Medullary thyroid carcinoma(MTC) • Multiple Endocrine Neoplasia syndrome type 2 (MEN2) • Pregnancy and breast-feeding • Gastroparesis, Hx of Pancreatitis • • • • • GI: Diarrhea Constipation Bloating Nausea Vomiting • Injection site irritation • Headache • Dizziness • Fatigue DPP-4 Inhibitors MOA Incretin hormones are released by the intestines throughout the day with the intake of food to help regulate increases in insulin secretion and decrease in glucagon secretion. These medications inhibit the DPP-4 enzyme preventing it from breaking down incretin hormones, and glucagon-like peptide 1 (GLP-1) allowing them to regulate the glucose by increasing insulin release and decreasing glucagon secretion Counselling points Generic (-gliptin) Brand Dosing Advantages Contraindications Common side effects Monitoring Linagliptin (Tradjenta) 5 mg once daily • • • • Saxagliptin (Onglyza) 2.5 to 5 mg once daily Sitagliptin (Januvia) 100 mg once daily Alogliptin (Nesina)  Advise patient to report symptoms of pancreatitis (stomach pain, nauseas, vomiting, oil stool) 25 mg once daily Weight neutral Lower A1c 0.6-0.8% Low risk of hypoglycemia dose adjustments in renal impairment • History of serious hypersensitivity reaction • • • • • • Rash Peripheral edema Upper Respiratory Tract infections URTIs Nasopharyngitis Urinary tract infections (UTI) Headache • POC Glucose • A1C • Kidney function • Saxagliptin and Alogliptin have increased of CHF hospitalizations • Saxagliptin metabolized by CYP3A4/5. Mechanism of Action of SGLT2 inhibitors SGLT-2 Inhibitors MOA Sodium-glucose co-transporter-2 proteins are located in the proximal convoluted tubules (PCT) of the kidney. These SGLT-2 receptors reabsorb 90% of glucose when they are inhibited glucose reabsorption is decreased resulting in increased glucose excretion in urine Generic (-flozin) Brand Dosing Advantages Contraindication s Common side effects Monitoring Dapagliflozin (Farxiga) • 5 mg once daily • 10 mg once daily Canagliflozin (Invonka) • 100 mg once daily • 300 mg once daily • Weight loss (2-3 kg) • Lower A1c 0.5-0.8% • Modest BP lowering • • • • ESDR Dialysis UTIs varying degrees of renal impairment Empagliflozin (Jardiance) Ertugliflozin (Steglarto) • 10 mg once daily • 25 mg once daily • 5 mg once daily • 15 mg once daily • Low risk of hypoglycemia • Cardiovascular and/or renal benefits • Bladder cancer • Lower limb Amputations • Euglycemic DKA (Mycotic/bacterial) urinary infections • POC Glucose • A1C • Weight Practical insights  Best to be taken in the morning before the first meal  Advised patient of increase urine output during the first few weeks of starting an SGLT-2 • Blood pressure • Kidney function Alpha-Glucosidase Inhibitors • Acarbose and miglitol • MOA: Delays intestinal carbohydrate digestion and absorption by competitively inhibiting enzymes in the small intestine • Advantages: No to low risk of hypoglycemia, reduces postprandial hyperglycemia • Disadvantages: Flatulence, diarrhea, bloating/gas (70%), abdominal pain, frequent dosing schedule; modest efficacy (↓ A1C by 0.5-0.9%) • Contraindications: • • • • Inflammatory bowel disease, intestinal obstruction, or other GI disorders Cirrhosis of the liver Avoid use if Scr > 2 mg/dL(acarbose) DKA Meglitinides • Repaglinide (Prandin®), Nateglinide (Starlix®) • MOA: • Increase insulin secretion (they bind to a different location on the sulfonylurea receptor) • Short acting • Advantages: • Decrease postprandial glucose excursions, dosing flexibility, rapid onset of action • Disadvantages: • Hypoglycemia, weight gain, frequent dosing schedule, expensive, modest efficacy (↓ A1C by 0.5-1.0%) Case 1 Patient Jodi Foster was recently diagnosed with Type 2 DM(A1c 7.0) and has been prescribed metformin IR 1000 mg once daily. One week after initiating therapy, the patient reports experiencing uncontrolled diarrhea and an upset stomach. However, she remains committed to continuing metformin treatment. How will you manage her concerns today? (Select all the apply) A. Advise the patient to take metformin with a meal B. Decrease the dose to 500 mg daily C. Transition to Metformin ER 500 mg daily D.Discontinue metformin and initiate insulin therapy. Case 1 continued The patient was switched to Metformin ER. What are the key counselling points? (Select all that apply) A. You may observe an empty shell of the extended-release tablet in your stool B. Expect to experience increased appetite and some weight gain 2-3 kg. C. Monitor for signs of low blood sugar D. Avoid alcohol with this medication Case 2 A 42-year-old patient presents with tachycardia and trembling. The patient seems to be confused and says his glasses don’t seem to be working. PMH includes type1 DM, HTN and Gerd. He uses meal time and basal insulin at home. He reports glucose readings at home between 180-200 mg/dL. He barely started treatment two weeks ago. POC blood glucose levels are 84 mg/dL. Is this patient experiencing hypoglycemia? A. No, Patient’s glucose is >70 mg/dL and his levels at home are very high putting him at little to no risk of hypoglycemia from insulin. B. Yes, Patient’s glucose is <100 mg/dL. C. No, Patient’s symptoms correlate with hyperglycemia only. D.Yes, although blood glucose level is >70 mg/dL the patient typically runs high and the drop to 84 mg/dL is manifesting as hypoglycemic symptoms. Case 3 Johnny Smith is a 21-year-old patient who presents to the clinic. Over the past few weeks, report he been drinking a lot of water and is constantly running to the restroom at school. He said he thinks he has lost weight and also noticed that he seems more irritable than usual. Vitals BP 120/74mmHg Temp 35.80C, O2 sat 98%. Height 5’9 ft weight 192 lbs. Lab results reveal an A1C of 9% and a random glucose of 300 mg/dL. The patient is diagnosed with type 1 diabetes. The provider wants to start long acting insulin. Which of the following insulin will you recommend? A. Start insulin glargine B. Start insulin lispro C. Start insulin aspart D. Start regular insulin Case 4 What is the mechanism of action of Ozempic? A. Ozempic mimetic incretin hormone bind to activate GLPI receptors ↑ insulin secretions, ↓ glucagon secretions, slowing gastric emptying. B. Ozempic inhibits the DPP-4 enzyme by prolonging incretin action, ↑ insulin release and decreasing glucagon secretion C. Ozempic decreases hepatic glucose production (gluconeogenesis) D. Ozempic binds to PPAR-gamma receptors in muscles, adipose tissue and the liver leading to an increase in insulin sensitivity and glucose uptake in muscle and adipose tissue which decreases glucose production in the liver Peroxisome proliferator-activated receptor gamma Case 5 Patient George Tayson 48-year-old male presents with unrolled diabetes. His A1C was 8.2%. random glucose was 200 mg/dL. PMH: Type 2 DM, pancreatitis, heart failure (LVEF 32%) Medications: Metformin 1000 mg twice per day, Furosemide 40 mg once per day, Valsartan 160 mg twice per day, metoprolol succinate 50 mg daily. What additional medication would you recommend for this patient? A. Dapagliflozin 10 mg B. Ozempic 0.25 mg C. Pioglitazone 15mg daily D.Saxagliptan 100 mg daily