Overview of Diabetes Medications Marie Frazzitta DNP, FNP c, CDE, MBA Senior Director of Disease Management North Shore LIJ Health Systems Normal Glucose Metabolism Insulin is produced by beta cells in the pancreas Insulin binds to its receptor on the target cell to allow for glucose entry into the cells Glucose Regulation Insulin Hyperglycemia Normal Range Hypoglycemia Glucagon Diabetes Educational Services 1
Diabetes is a metabolic disease In which the body can not make insulin Beta Cell Failure Type 1 Diabetes Is unable to utilize the insulin it makes Insulin Resistance Type 2 Diabetes Or both Beta Cell Dysfunction and Insulin Resistance Type 2 Diabetes Diabetes Types Key characteristics of type 1, LADA, and type 2 Type 1 LADA Type 2 Typical age of onset Youth or Adult Adult Youth or Adult Progression to insulin dependence Immediate Latent (months/years) Slow Presence of autoantibodies Yes Yes No Insulin dependence Yes/ at diagnosis Yes Over time, if at all Insulin resistance No Possible Yes Medications Used for Diabetes Medication Class Biguanide Sulfonylurea 2nd Gen Glipizide, Meglinide Thiazolidinedione α glucosidase inhibitor SGLT2 inhibitor DPP 4 Inhibitor GLP 1 agonist Amylin mimetic Insulin Metformin Medications Glyburide, Glimepiride Repaglinide, Nateglinide Pioglitazone, Rosiglitazone Acarbose, Miglitol Canagliflozin, Dapagliflozin, Empagliflozin Sitagliptin, Saxagliptin, Linagliptin, Alogliptin Exenatide, Liraglutide Pramlintide Various 2
Biguanide TZD Insulin SU/Meglinides DPP 4 Inhibitor GLP 1 agonist Amylin Mimetic α Glucosidase Inhibitor Biguanide TZD Circulatory System Glucose FFA Kidney TZD Biguanide SGLT inhibitor Promotes Blocks What is an Hemoglobin A1C number? Each % changes approx 30 points Biguanide Medication(s) Metformin (Glucophage ) How does it work? Decreases hepatic glucose production Increases peripheral insulin sensitivity A1C reduction 1 2% Contraindication (CI) Side Effects Comments Serum creatinine (mg/dl)male 1.5 or female 1.4 Acute or chronic acidosis, Hepatic dysfunction Excessive alcohol intake, Type I DM, Diabetic ketoacidosis (DKA) Weight loss, nausea, vomiting, epigastric pain, bloating, gas Max daily dose: 2550mg Start at 500mg daily and titrate up every 1 2 weeks Precaution with iodine containing contrast dye May improves lipid profile (decrease TG, LDL, Total cholesterol and Increase HDL) 3
Medication(s) How does it work? Sulfonylurea Glyburide (Diabeta ; Glynase ) Glipizide (Glucotrol ) Glimeperide (Amaryl ) A1C reduction 1 2% Contraindicated Type I DM, DKA Increase the release of insulin from the pancreas Side Effects Comments Hypoglycemia, weight gain All renally cleared Glyburide on Beers Criteria Caution in irregular eating pattern Medication(s) How does it work? A1C reduction 0.5 1.5% Contraindicated Type I DM, DKA Meglinides Repaglinide (Prandin ), Nateglinide (Starlix ) Increase the release of insulin from the pancreas Side Effects Comments Hypoglycemia, weight gain Take before meals No meal No medication (Repaglinide) caution with renal and hepatic impairment Thiazolidinediones Medication(s) How does it work? Pioglitazone (Actos ), Rosiglitazone (Avandia ) Improves insulin sensitivity Decreasing free fatty acids A1C reduction 0.5 1.4% Contraindicated Side Effects Comments NYHA Class III/IV heart failure, active liver disease Type I DM, DKA Weight gain, fluid retention, bone fractures, hepatic impairment Takes about 8 12 weeks to achieve maximum effect May improves lipid profile (Increase HDL, Decrease triglyceride) 4
Sodium Glucose co Transporter 2 Inhibitor (SGLT2 inhibitor) Medication(s) How does it work? Canagliflozin (Invokana ), Dapagliflozin (Farxiga ), Empagliflozin (Jardiance ) Reduces reabsorption of glucose in the kidney Lowers renal threshold for glucose excretion A1C reduction 0.8 1% Contraindicated Severe renal impairment, dialysis, Type I DM, DKA Side Effects Urinary tract infection, female genital infection Comments All once a day medication Taken with or without food DPP 4 inhibitor and GLP1 agonist Incretin or GLP1 Stimulates insulin release Inhibits glucagon release Goal Lowering Blood Glucose DPP 4 inhibitor Prevents enzymes effect DPP 4 enzyme Breaks down GLP Medication(s) How does it work? Dipeptidyl Peptidase 4 inhibitor (DPP 4 Inhibitors) Sitagliptin (Januvia ), Saxagliptin (Onglyza ), Linagliptin (Tradjenta ) Inhibits breakdown of incretin, glucagon like peptide 1 (GLP 1) Reduces glucagon secretion Slows GET, promotes satiety A1C reduction 0.5 0.8% Contraindicated Pancreatitis Type I DM DKA Side Effects Hypoglycemia when used with insulin Comments Renally dosed except for linagliptin All once a day medication Taken with or without food 5
GLP 1 Agonist (Incretin Mimetic) Medication(s) How does it work? Exenatide (Byetta, Bydureon ), Liraglutide (Victoza ) Increases glucose dependent insulin secretion Reduces glucagon secretion Slows gastric emptying time (GET),promotes satiety A1C reduction 0.5 1.1% Contraindicated Medullary thyroid carcinoma, multiple endocrine neoplasia syndrome Type 2, Type I DM, DKA Side Effects Hypoglycemia, pancreatitis, acute renal failure, nausea/vomiting/diarrhea, weight loss Comments Only used to treat Type 2 diabetes Available in injectable pen form Should be discarded within 30 days after its use Amylin Mimetic Medication(s) Pramlintide (Symlin ) How does it Reduces glucagon secretion work? Slows gastric emptying time (GET),promotes satiety A1C reduction 0.5 1% Contraindicated Hypoglycemia unawareness, confirmed gastroparesis, DKA Side Effects Hypoglycemia unawareness, headache, nausea, vomiting, weight loss Comments Dose of medication depends on the type of DM Pramlintide alone does not cause hypoglycemia Insulin dose decreased by 50% Taken before meals take contain at least 250calories or 30 gram of carbohydrates Insulin Preparations Insulin preparations Brand name Type Onset of action Peak Duration of action Rapid acting (administer immediately before meal) Humalog Insulin lispro 5 15 min 0.5 1.5 hr 3 5 hr Novolog Insulin aspart 5 15 min 0.5 1.5 hr 3 5 hr Apidra Insulin glulisine 5 15 min 0.5 1.5 hr 3 5 hr Short acting (administer 30 min before meal) Humulin R Novolin R Regular human insulin 30 60 min 2 3 hr 5 8 hr Intermediate acting Humulin N Novolin N Isophane insulin suspension (NPH) 2 4hr 4 10hr 10 16hr Long acting Lantus Insulin glargine 2 3hr None 20 24hr Levemir Insulin detemir 1 2 hr None Dose dependent ~6 23 hr Premixes Humalog mix 75/25 75% lispro protamine suspension 5 15 min Dual 10 16hr (NPL)/25% lispro Novolog mix 70/30 70% protamine crystalline 5 15 min Dual 10 16hr aspart/30% aspart Humulin 70/30 70% NPH/30% regular 30 60 min Dual 10 16hr Novolin 70/30 Humalog mix 50/50 50% NPL/50% lispro 5 15 min Dual 10 16hr Concentrated Insulin Humulin U 500 Regular human insulin 500 units/ml 30 min 1 3 hr 8 24 hr 6
The Duration of Action of Insulin O:5 15min / D:3 5 hours O:30 60min / D:5 8 hours O:2 4 hours/ D:10 16 hours O:1 2 hours/ D:6 23 hours O:2 3 hours/ D:20 24 hours Legend: O=Onset / D=Duration How do we use different type of insulin? How do we use different type of insulin? 7
Mixing Insulin INSULIN TYPE OF INSULIN APPEARANCE Lispro (Humalog ) Clear Aspart (Novolog ) Rapid Clear Glulisine (Apidra ) Clear Regular (Novolin R or Humulin R ) Short Clear NPH (Novolin N or Humulin N ) Intermediate Cloudy FIRST clear-short acting THEN cloudy-longer acting Gently mix cloudy insulin Dosing SQ Insulin TOTAL DAILY TYPE OF PATIENT INSULIN DOSE 0.3 UNITS/KG Lean patients (BMI<18.5 or at high risk of hypoglycemia ) 0.4 UNITS/KG Normal (BMI 18.5 24.9) 0.5 UNITS/KG Overweight patients (BMI 25 29.9) 0.6 UNITS/KG Obese patients (BMI>30) or highly insulin resistant Calculating SQ dose Calculate Total Daily Dose 50% Basal /50% Meals 33%Breakfast / 33%Lunch / 33% Dinner Patient s: BMI 32 / weight 100kg 0.6units/kg x 100kg = 60 units total daily dose Basal dose 60 / 2 = 30 unit Lantus once a day Meal Dose 30/3 = 10units Humolog before each meal Determine how much patient is eating 8
Which medications can cause low blood sugar? Insulin Sulfonylurea Meglitinides GLP 1 agonist Amylin mimetic 15:15 Rule Treatment of Blood sugars of <70 START When <70mg/dL Glucagon Allows the breakdown of glycogen into glucose Treatment dose for hypoglycemia >20 kg : 1 mg (1 unit) subcutaneous, IM or IV <20 kg: 0.5 mg (0.5 unit) subcutaneous, IM or IV 9
Clinical Use 80yo M with Type 2 Diabetes is required to receive angiogram with contrast. Which medication should be discontinue? A. Glipizide B. Repaglinide C. Metformin D. Acarbose Clinical Use Which diabetes medication can cause weight gain and fluid retention? A. Rosiglitazone B. Repaglinide C. Insulin D. Glipizide Clinical Use 300lb patient is newly diagnosed with Type 2 Diabetes. The patient s hemoglobin A1C is 8%. Which medication is most appropriate for this patient? A. Glipizide B. Insulin C. Metformin D. Rosiglitazone 10
Medications that affect weight Decrease Exenatide (Byetta ) Liraglutide (Victoza ) Pramlintide (Symlin ) Metformin (Glucophage ) Increase Sulfonylureas Meglitinides Insulins Thiazolidinediones Clinical Use 90yo M with Type 2 Diabetes was readmitted for a fall at home. On admission the blood sugar was 50mg/dL and later on labs showed his A1C to be 5.5%. Which medication most likely caused his hypoglycemia? A. Glyburide B. Sitagliptin C. Metformin D. Rosiglitazone Which medications can cause low blood sugar? Insulin Sulfonylurea Meglitinides GLP 1 agonist Amylin mimetic 11
Clinical Use Which Medicare part covers diabetes medications and diabetes supplies (syringe, needle, alcohol swabs, gauze)? A. Medicare Part A B. Medicare Part B C. Medicare Part C D. Medicare Part D Reference: Medicare coverage for Diabetes at a Glance Clinical Use Which Medicare part covers blood sugar testing equipment and supplies? A. Medicare Part A B. Medicare Part B C. Medicare Part C D. Medicare Part D Reference: Medicare coverage for Diabetes at a Glance Medications that can cause Hyperglycemia Cortiosteroids Atypical antipsychotics (such as Clozapine, Risperidone, Olanzapine, Quetiapine) Niacin Beta blockers Protease inhibitors 12
Medication in regards to food With Food Metformin Sulfonylurea Meglitinides Alphaglucosidase inhibitor Amylin mimetics Rapid acting insulin Exenitide Doesn t matter Thiazolidinediones DPP 4 Inhibitor Liraglutide Sandra is a 26 year old woman with type 1 diabetes. She is a school teacher and has a very active social life. Her insulin dosage is 18 units of lantus HS and an Insulin to carbohydrate ratio of 1:10 for breakfast and 1:15 for lunch and dinner. She came in today because for the last week she has been waking up with high fasting levels. She had recently lost about 10 lbs. Fasting After Breakfast Before Lunch After Lunch Before Dinner 222 188 88 115 145 188 110 200 225 265 222 45 134 112 202 145 99 76 110 302 288 135 38 223 198 112 155 100 119 201 165 88 After Dinner JR has type 2 diabetes. BMI 32. He is currently taking metformin 1000mg QD and Januvia 100mg daily. He is a long distance truck driver and works many hours. He came in today for his regular visit. Fasting After Breakfast Before Lunch After Lunch Before Dinner After Dinner 163 256 110 225 350 145 156 88 234 125 212 156 222 98 115 88 160 128 118 229 198 13
ML has type 2 diabetes. He is on Metformin 2000mgqd and prandin 1mg ac meals. His last HbA1c was 8.6%. Below is his log book and food diary. Dates Fasting After Breakfast Before Lunch After Lunch Before Dinner After Dinner 5/1 135 220 100 118 88 124 5/2 122 166 134 152 5/3 165 198 112 147 101 144 5/4 119 188 121 119 5/5 118 156 188 99 166 Take Home Points Know the medication class characteristics Know the medication class side effects What is best for my patient??? Diabetes care should be individualized Questions? 14