Newer and Expensive treatment of diabetes Jyoti Bhattarai MD Endocrinology Visiting Associate Professor Institute of Medicine TUTH
Four out of every five people with diabetes now live in developing countries. most affected men and women being of working age. The average total cost per year incurred in the treatment and care of diabetes was found to be NRs.32102
Which is more important????? Diet Exercise Monitoring Feet care Dental care Regular eye check up Smoking cessation Statins Oral hypoglycemic agents Antihyperte nsive(ace-i or ARB)
Pathphysiologyof typ2 diabetes Insulin resistance Beta cell dysfunction Increased liver glucose production Other factors Impaired incretineffect Glucagon effect Increased rate of gastric emptying
Incretinbased therapy
Normal Physiologic Actions of GLP-1 Brain Neuroprotection Appetite Heart Stomach Gastric emptying Cardioprotection Liver* Cardiac output GLP-1 GI tract Pancreas Insulin biosynthesis β-cell proliferation Insulin sensitivity β-cell apoptosis Glucose production Muscle* Insulin secretion Glucagon secretion In a glucose dependent fashion! * GLP-1 actions on liver and muscle are indirect ; Drucker DJ. Cell Metab 2006;3:153-165 3
Newer / expensive sugar control Incretinbased therapy GLP-1 receptor agonist DipeptidylPeptidase inhibitors Insulin pump
Updated ADA/EASD Consensus Algorithm STEP 1 STEP 2 STEP 3 Tier 1: Well-validated therapies At Diagnosis: Lifestyle + Metformin Lifestyle + Metformin + Basal Insulin Lifestyle + Metformin + Sulfonylurea a Tier 2: Less well-validated therapies Lifestyle + Metformin + Pioglitazone Lifestyle + Metformin + Pioglitazone + Sulfonylurea a Lifestyle + Metformin + Intensive Insulin Lifestyle + Metformin + GLP-1 agonist b Lifestyle + Metformin + Basal Insulin Reinforce lifestyle interventions at every visit and check A1C every 3 months until A1C <7.0%, then at least every 6 months thereafter. Change interventions whenever A1C 7.0%. a Sulfonylureas other than glybenclamide (glyburide) or chlorpropamide. b Insufficient clinical use to be confident regarding safety. Nathan DM, et al. Diabetes Care. 2008;31:1-27
Incretomimetics Exanatide Liraglutide Exenatide LAR Taspoglutide Incretin enhancers Sitagliptin Saxagliptin Vildagliptin Linagliptin Incretins
GLP-1 Regulates Central Feeding Behavior
GLP-1 (incretin mimetic agent) Improves beta-cell responsiveness to increasing glucose levels Decreases glucagon secretion Slows gastric emptying Results in a feeling of fullness Must be injected subcutaneously twice a day for Exenatide, within 30-60 minutes before a meal Once a day with liraglutide. Reduces HbA 1c by ~1%
Side effects Nausea, vomiting, diarrhea Dyspepsia Hypoglycemia Headache Dizziness Acute Pancreatitis C-cell hyperplasia
GLP-1 (incretinmimetic agent) Contraindications End-stage kidney disease or renal impairment Pregnancy Severe gastrointestinal disease
Case exampless 49 years old female, came to the clinic with the help of 2 sisters, walking with a cane, BP 120/80, weight 105 kg, BMI 42 On metformin1000gm twice daily. Blood sugars 120 fasting and 150 PP, hgba1c 6.7%. Liraglutide given, weight 86kg, patient walking one hour every day, fasting 96, pp 130.
Dipeptidylpeptidase 4 inhibitors Decrease A1c about 1 %. Weight neutral No major side effects Expensive May have cardioprotectiveeffects.
DPP-4 Inhibitors (dipeptidylpeptidase-4 ) Januvia(sitagliptin), Onglyza(saxagliptin), (Galvus) (Vildagliptin) A1c 0.5-0.8% FPG 15-30 mg/dl PPG 34-50 mg/dl Dosing: sitagliptin50 or 100 mg daily, saxagliptin2.5 or 5 mg daily, linaglipitin 5 mg daily (Taken with or without food)
Change in Body Weight Over 24 Weeks: Sitagliptin Monotherapy Studies
Advantage Less blood sugar monitoring Tolerability Weight loss /weight neutral Beta cell preservation Minimize hypoglycemia
Side effects hypoglycemia when used with insulin or insulin secretagogues nasopharyngitis upper respiratory infections all-cause infections headache gastrointestinal symptoms musculoskeletal pain
Cost of these medicines 250 dollars per month Sitagliptin 80 Rupees per pill, about one US dollars.
Sitagliptin (Januvia) Vildagliptin (Galvus) Saxagliptin(Onglyza) Common side effects nasopharyngitis, upper respiratory tract infection, headache nasopharyngitis, upper respiratory tract infection, headache nasopharyngitis, upper respiratory tract infection, headache Watch out for Increase in WBC counts, increase in Serum creatinine, Allergic reactions, Hepatic dysfunction Edema, Hepatic dysfunction, skin reactions in renal failure Lymphocyte counts fall/ caution with TZD over CFF Drug interactions None significant. Watch with Digoxin, Warfarin and Simvastatin Not significant/ OK with all main drugs classes Not significant/ OK with all main drugs classes Dosing 100 mg/day ( tablets as 25,50,100) 50-200 mgs /day ( usual dose is 50 mg/day) 2.5-10 mgs
Insulin Pumps and Sensors Minimed Paradigm
Quickly identify patterns Daily statistics