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Best Practice Diabetes Drug Management Secrets-2014

Best Practice Diabetes Drug Management Secrets-2014. Loss of Eyesight. Diet/Exercise/Lows/Kidneys/Nerve/ED/Depression. Foot Amputation . By Sharon A. Watts DNP, RN-BC, CDE. Disclaimers. I have no affiliations with drug companies I have no affiliations with any industry.

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Best Practice Diabetes Drug Management Secrets-2014

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  1. Best Practice Diabetes Drug Management Secrets-2014 Loss of Eyesight Diet/Exercise/Lows/Kidneys/Nerve/ED/Depression Foot Amputation By Sharon A. Watts DNP, RN-BC, CDE

  2. Disclaimers • I have no affiliations with drug companies • I have no affiliations with any industry • I do believe decisions about drugs should be based on evidence, cost to society and individual patient lifestyle & benefit vs. risk

  3. Objectives • Identify common prescribing rules for diabetes drugs. • Select diabetes therapies for several case study presentations based on best practice prescribing knowledge.

  4. Fact or Fiction?New Patient -65 year old DM x 12 years, LDL-145, A1c 11%, B/P 162/85, microalbumin/creatinine ratio 200 The Most Important Thing I can do for my patient with diabetes today if I only have time for one change today it should be to lower his high A1c?

  5. Treating the ABCs Reduces Diabetic Complications 1 UKPDS Study Group (UKPDS 33). Lancet. 1998;352:837-853. 2 Hansson L, et al. Lancet. 1998;351:1755-1762. 3 UKPDS Study Group (UKPDS 38). BMJ. 1998;317:703-713. 4 Grover SA, et al. Circulation. 2000;102:722-727. 5 Pyŏrälä K, et al. Diabetes Care. 1997;20:614-620.

  6. Estimated time to benefit Glucose control 8 years Blood pressure control 2-3 years Lipid control 2-3 years While glucose and lipid management remain important, blood pressure lowering has the greatest and most immediate impact on morbidity and mortality (52 [EL 1; RCT], 326 [EL 1; RCT, AACE Guidelines-2011 Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 38. UK Prospective Diabetes Study Group [Erratum in: BMJ. 1999;318:29]. BMJ. 1998;317:703-713. [EL 1; RCT] Holman RR, Paul SK, Bethel MA, Neil HA, Matthews DR. Long-term follow-up after tight control of blood pressure in type 2 diabetes. N Engl J Med. 2008;359:1565-1576. [EL 1; RCT, questionnaires and other variables may have confounded]

  7. 100 Non overweight Overweight 80 HOMA %B 60 40 20 Beta cell loss ~4% per year 0 0 1 2 3 4 5 6 0 1 2 3 4 5 6 Years from randomisation Conventional Sulphonylurea Metformin Progressive Decline in Beta Cell Function UKPDS 16. Diabetes 1995; 44: 1249-58

  8. Non-Insulin Therapy for Hyperglycemia in Type 2 Diabetes - - - Peripheral glucose uptake 1.Pancreatic insulin Secretion: Incretin, ranolazine 5.Gut CHO Absorption: Incretin, Pramlintide, Glucosidase inh. 7.Brain- TZD,INCRETIN, bromocryptine 2.Pancreatic glucagon Secretion- Incretin 8.Kidney- SGLT2 HYPERGLYCEMIA De 3.Muscle- TZD, Incretin Hepatic glucose production : Metformin, incretin 4.Liver 6.Fat- TZD, metformin

  9. Metformin-The Pinnacle of Sweet Success

  10. BIGuanides Metformin Cardiovascular benefit Decrease A1c by 1.0 – 2.0 No hypoglycemia Cannot be used in renal failure (Cr Cl < 30 ml/min, s. creat> 1.5 in males, > 1.4 in females) Adverse effects: nausea, vomiting, diarrhea, lactic acidosis, B12 deficiency Generic available Use Metformin SA!!!!

  11. https://www.aace.com/files/algorithm-07-11-2013.pdf p. 12 accessed 12.16.13

  12. AACE Metformin Recommendations • This limitation has been challenged, however, and lower doses have been proposed for patients with moderate renal insufficiency (126). • The AACE agrees with the Kidney Disease: Improving Global Outcomes 2012 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease recommendations, which state that metformin should be continued in patients • with an eGFR ≥45 mL/min/1.73 m2 (GFR categories G1-G3a), • that its use should be reviewed in those with an eGFR of 30 to 44 mL/min/1.73 m2 (GFR category G3b), • and that it should be discontinued in patients with an eGFR <30 mL/min/1.73 m2 (GFR categories G4-G5) (127).

  13. METFORMIN-Lactic acidosis • Conditions that cause a hypoxemic state: • Renal insufficiency • Concurrent liver disease or alcohol abuse (sgot/sgpt 2x ULN) • Heart failure (stage III & IV) • History of lactic acidosis • Decreased tissue perfusion or hemodynamic instability • Hypoxic or acute illness

  14. Sulfonylureas Increase insulin secretion Decrease A1c by 1.0 – 2.0 Risk of hypoglycemia(5x that of metformin only) Can be used in mild renal failure, however risk of hypoglycemia more Skip a meal, skip a dose Adverse effects: minimal Generics available

  15. Sulfonylureas • Glipizide • Short acting-need to take ½ hr. prior to meal • Lesser risk of hypoglycemia • Safer than other sulfonylureas in older subjects • Can be used in mild renal failure(CrCl <10) • Change to other medications if renal failure worsens or if hypoglycemia with renal failure

  16. Sulfonylureas • Glyburide • Longer acting-can take right w/meal • Stronger potency than glipizide • Increase risk of hypoglycemia • Not recommended if Cr Cl < 50 ml/min • Glimepiride(generic now) • Can given once daily dose with meal • Can be used in mild renal failure(CrCl <10)

  17. Use of sulfonylurea as second-line therapy for type 2 diabetes generated glycemiccontrol and QALYs comparable with those associated with other agents but atlower cost.Diabetes Care February 26, 2014 http://care.diabetesjournals.org/content/early/2014/02/18/dc13-1901.long

  18. Nonsulfonylurea Secretagogue • Repaglinide (Prandin), Nateglinide (Starlix) • MOA • Stimulate glucose-dependent release of insulin by closing the ATP-dependent K+ channels of the pancreatic beta-cells • Shorter half life than SU • A1c lowering • 0.5-1% • If the meal is skipped, then omit dose • Take medication just prior to eating a carbohydrate meal. Cont’d…

  19. Nonsulfonylurea Secretagogue • Indications • Monotherapy with diet • Combination with metformin & TZD • Benefits • Decrease in post-prandial glucose • Short half-life • May demonstrate less hypoglycemia than SU • Use Caution: co-administration of repaglinide with gemfibrozil is contraindicated. (Gemfibrozil is a hepatic enzyme inducer, therefore repaglinide level could be increased). …cont’d Cont’d…

  20. Nonsulfonylurea Secretagogue • Patient Type • Pt with more predominant post-prandial hyperglycemia • Pt with hypoglycemia episodes on SU • Pt with less consistent food plan • Not for the pt with SU failure & persistently above glycemic goals …cont’d

  21. Thiazolidinediones (TZDs) • Pioglitazone (Actos) & Rosiglitazone (Avandia) • Alters transcription of genes that regulate carb and lipid metabolism • Increase insulin stimulated glucose uptake by muscle cells • Decrease insulin resistance in peripheral tissues Cont’d…

  22. Thiazolidinediones(TZDs)…cont’d • Contraindicated - NYHA Class III and IV Heart Failure Precautions • Concurrent use of insulin or nitrates (rosiglitazone) • Hepatic dysfunction • Cardiovascular Dx • Side Effects • Weight gain • Edema • Exacerbate or lead to HF • Risk of bone fracture • Pioglitazone is associated with a small risk of bladder cancer. • Restricted access to rosiglitazone due to concerns about cardiovascular safety. • A1c lowering (1-1.5%)

  23. Case Study Break New Patient -65 year old DM x 12 years, LDL-105, A1c 11%, B/P 122/85, BMI-44 microalbumin/creatinine ratio 200 Meds-Glipizide 10 mg BID, Metformin 1 gm BID Blood Glucose: AM Lunch Dinner HS 291 220 301 195 247 267 299 178 288 351 251 333 356 No lows

  24. GLP-1 Agonists(liraglutide and exenatide)MOA Oral glucose stimulates GLP-1 & GIP Incretin Hormones DPP-4 Inhibitors rapidly degrade the incretin hormones GLP-1 agonist bind to GLP-1 receptors GLP-1 agonists are not susceptible to DPP-4 Blood Glucose Body Cell Decrease Appetite Stomach Insulin Receptor Liver Insulin Pancreas Decrease Glucagon Increase Insulin Decrease Gastric Emptying

  25. GLP-1 Agonists • A1c lowering- Adding a GLP-1 agonist to metformin or SU resulted in mean decrease in A1c ranging from 0.8-1.0% • Not susceptible to DPP-4 degradation • Increases Insulin secretion only in response to glucose load or elevated glucose concentration • Given as a subcutaneous injection • Side effects: nausea/hypoglycemia/wt. loss • Avoid use in patients with history of pancreatitis • Liraglutide is associated with thyroid C cell tumors in rodents, but unknown in humans VA/DoD Guidelines http://www.healthquality.va.gov/diabetes/DM2010_FUL-v4e.pdf

  26. Reference - GLP-1 Agonists Byetta PI. 12/2011 Victoza PI. 4/2012. Bydureon PI. 1/2012

  27. DPP-4 Inhibitors • Prevent the degradation of GLP-1 • Do not affect: • Satiety • GLP-1 effects on gastric emptying • A1c lowering an average of 0.5-0.7% as monotherapy-efficacy of DPP-4 inhibitors appears to decline after 1 year of treatment. • Once daily dosing • Dose adjustment in renal dysfunction • Sitagliptin: • Possible association pancreatitis • Evaluated with insulin VA/DoD Guidelines http://www.healthquality.va.gov/diabetes/DM2010_FUL-v4e.pdf

  28. Reference DPP-4 Inhibitors • Linagliptin is administered 5mg orally once daily either as monotherapy or in combination with metformin, sulfonylureas, or TZDs. • It may be taken with or without food. • No dosage adjustment is needed for renal or hepatic insufficiency. • Monitoring- AIC, Renal Function National PBM medication VHA Pharmacy Benefits Management Services and Medical Advisory Panel http://www.pbm.va.gov/medicationMonograph.aspx Adapted from:Wigle PR et al. PSAP VII, verified from Thomson Micromedex Accessed 3/25/11.

  29. Discontinuation Criteria • These agents are not to be used in patients with history of pancreatitis. • Pancreatitis has been reported with the DPP-4 inhibitors. Monitor patients carefully for the development of pancreatitis after initiation or dose increases of agent. Discontinue agent if pancreatitis is suspected while using these products. • Serious allergic and hypersensitivity reactions (e.g. anaphylaxis, angioedema, exfoliative skin conditions including Stevens-Johnson syndrome) have been reported with the DPP-4 inhibitors.  If these reactions occur, discontinue agent and initiate alternative treatment for diabetes. • Consider lowering insulin or Sulfonylurea dose if DPP4 inhibitor is initiated. Dipeptidyl-peptidase-4 (DPP-4) Inhibitors: Sitagliptin, Saxagliptin, and Linagliptin Criteria for Use http://www.pbm.va.gov/CriteriaForUse.aspx Dipeptidyl-peptidase-4 (DPP-4) Inhibitors: Sitagliptin, Saxagliptin, and Linagliptin Criteria for Use http://www.pbm.va.gov/CriteriaForUse.aspx National PBM medication VHA Pharmacy Benefits Management Services and Medical Advisory Panel http://www.pbm.va.gov/medicationMonograph.aspx

  30. SGLT2 Inhibitor Drug Class SGLT2 Protein that absorbs glucose for energy for body SGLT2 inhibitors work by preventing the reabsorption of glucose in the kidneys canagliflozin and dapagliflozin FDA Approved side effects include genital and urinary tract infections and decreases in bone density • This can cause the expulsion of 100 to 300 calories of excess glucose each day. • Clinical trials for SGLT2 candidates have all shown weight loss.

  31. Insulin Stepwise Logic

  32. Multiple injections of insulin: Basal bolus plan

  33. Kinetics of Long-Acting Insulin NPH Detemir Plasma Insulin Levels Glargine 0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 “Basal” insulin; NOT meal coverage. Can/should give even when NOT eating!

  34. Initiating Basal Insulin • Generally start 0.1-0.2 Units/kg • Titrate 10-20% at a time (every 2-7days) until target range, or any low blood sugar • Rotate injection sites • Do not shake N too hard • Check fasting and before meal Blood Sugars to identify if basal dose correct

  35. Teach Mobility of Injection Sites!

  36. Prandial Insulin • No set rules for initiation but safe practice is 1 unit per CHO consumed • May be able to start daily or twice daily • Titrate based on 2 hour pre/ post-prandial level

  37. Kinetics of Short-Acting Insulin Aspart, lispro, glulisine • SAI Use • Meal Coverage • Regular may be useful for pt who “grazes” Plasma Insulin Levels Regular 0 1 2 3 4 5 6 7 8 9

  38. Hypoglycemia • Some dangerous sequelae of hypoglycemia: • tachycardia • bradyarrhythmias • frequent ventricular ectopic beats • ST depression • T-wave flattening • QT prolongation Kodl C.T. & Seaquist E. R. (2008) Practical strategies to normalize hyperglycemia without undue hypoglycemia in Type 2 diabetes mellitus. Current Diabetes Reports 8, 375- 382.

  39. Hypoglycemia (cont.) • Studies have also shown the effects of diminished subsequent hypoglycemia response after a first episode (even in those without diabetes).  • The compensatory increase in cortisol production during a first hypoglycemic episode may play a central role in minimizing the protective hormonal responses during a subsequent episode Davis S.N. Mann S. Briscoe V.J. Ertl A.C. & Tate D. B. (2009) The effects of intensive therapy and antecedent hypoglycemia on counter regulatory responses to hypoglycemia in type 2 diabetes. Diabetes 58 701-705.

  40. Hypoglycemia (cont.) • If the blood glucose falls to 50 mg/dL (2.8 mmol/L), transient cognitive deficits may also ensue, which can result in falls or aspiration. • If the blood glucose falls <40 mg/dL (2.2 mmol/L), seizure or coma may ensue. Ben-Ami, H., Nagachandran, P., Mendelson, A.,andEdoute, Y. 1999. Drug-induced hypoglycemic coma in 102 diabetic patients. Arch. Intern. Med. 159:281–284. Cryer, P.E. 2001. The prevention and correction of hypoglycemia. In Handbook of physiology. Section 7,The endocrine system. Volume 2, The endocrine pancreas and regulation of metabolism. L.S. Jefferson and A.D. Cherrington, editors. Oxford University Press. New York, New York, USA. 1057–1092.

  41. Key Take Home Points • View BS’s in a daily pattern • Use ½ dose of SU-Clinically effective dose • Use Metformin or Metformin SA-think compelling reason NOT to be on it • Start basal insulin early (UKPDS-6 yrs-50%) 0.1 U/kg • 9-9-9 Rule of starting basal insulin • Start bolus insulin early if needed 12~15 yrs-1 unit per CHO-check 2 hr PP levels • Titrate insulin 10~20% at a time • If not on orals 50-50% mix basal/bolus to control blood glucose • Avoid Hypoglycemia

  42. Resources

  43. http://www.consumerreports.org/health/resources/pdf/best-buy-drugs/Diabetes-2pager-March2009.pdf accessed 1.3.14

  44. Types of Insulin http://diabeteshealth.com/media/pdfs/PRG0113/Insulin.pdf

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