Diabetes Medications. Minal Patel, PharmD, BCPS

Transcription

1 Diabetes Medications Minal Patel, PharmD, BCPS

2 Objectives Examine advantages and disadvantages of oral anti-hyperglycemic medications Describe the differences between different classes of insulin Explore the role of medications in treatment of diabetes Review medications on the Medicaid PDL Identify complications and co-morbid conditions associated with diabetes

3 Glycemic Goals Parameter Normal ADA ACE Pre-prandial <100 (mean 90) mg/dl <110 Post-prandial <140 <180mg/dL <140 A1c 4%-6% <7% <6.5% **Goals are different in pregnant women: Pre-prandial: <95mg/dL 1hr-post meal: <140mg/dL 2hr-post meal: <120mg/dL Adapted from American Diabetes Association: Standards of medical care in diabetes, Diabetes Care 37: 2014; and American College of Endocrinologists: American College of Endocrinology Medical Guidelines for Clinical Practice for the Management of Diabetes Mellitus, Endocr Pract 13(Suppl 1):16 34, 2007.

5 A1C Correlations Standard biomarker of glycemic control Average of blood glucose readings over 2-3 months Correlates well with microvascular complications

6 Drug Classes

7 Classes of Diabetes Medications Insulin Secretagogues Biguanides Thiazolidinediones Alpha-glucosidase Inhibitors DPP-4 Inhibitors GLP-1 Receptor Agonists Sodium Glucose Transport Inhibitors

8 Insulin Secretagogues Bind to specific ATP-sensitive potassium channels in the beta cell membrane and increases insulin secretion 70-80% effect on BG occurs half the max. doses Sulfonylureas Glyburide (Diabeta, Micronase, Glynase ) Glipizide (Glucotrol, Glucotrol XL ) Glimepiride (Amaryl ) AVOID glyburide in Elderly Meglitinides Repaglinide (Prandin ) Nateglinide (Starlix )

9 Biguanides Decreases liver production of glucose and decreases insulin resistance Metformin (Glucophage ) Glucophage XR 500 & 750 mg Glumetza XR 500 & 1000 mg Fortamet ER 500 & 1000 mg Metformin liquid (Riomet) 500mg / 5ml Advantages Effective and safe No CVD risk to date No weight gain and some weight loss No low blood sugar reaction Low cost Disadvantages GI side effects Lactic acidosis (rare) Monitor SCr liver failure, dye, surgery, heart failure, alcohol abuse Vitamin B12 may deplete

10 Thiazolidinediones (TZDs) Increases peripheral insulin sensitivity Pioglitazone (Actos ) FDA advisory issued September 2010 of increased risk of bladder cancer with pioglitazone use greater than 1 year Rosiglitizone (Avandia ) availability VERY limited Advantages Well tolerated No hypoglycemia as monotherapy Can use in renal disease Increases HDL cholesterol Disadvantages Weight gain (4-6lbs)/edema Delayed action 6-14 weeks Avoid: liver disease, CHF Risk of bone fractures Risk of heart attack or failure

11 Alpha-Glucosidase Inhibitors Acarbose (Precose ) and Miglitol (Glyset ) Blocks enzymes that digest starches in food Slower and lower rise in blood glucose Contraindicated in Inflammatory bowel disease, colonic ulceration, chronic intestinal disease or any intestinal obstruction Advantages Does not cause hypoglycemia as monotherapy Targets after meal high blood glucose Disadvantages GI effects due to undigested carbohydrates (abdominal pain, diarrhea, flatulence) Must treat hypoglycemia with glucose tablets and not other forms of sugar

12 Incretin Therapies: DPP- 4 Inhibitors and GLP-1 Agonists Glucose in diet activates incretins Incretins enhance glucose dependent insulinsecretion Works in the gut New therapies work to increase insulin release Delay in gastric emptying leads to hypoglycemia

13 DPP-4 Inhibitors DPP-4 Inhibitor Dosing Comments Sitagliptin (Januvia ) combo with metformin Janumet 50/500 and 50/1000, Janumet XR 50/1000 ) Saxigliptin (Onglyza ) combo with metformin Kombiglyze Linagliptin (Tradjenta ) Alogliptin (Nesina ) combo with metformin Kazano 100 mg daily orally Renal Dosing based on CrCl ml/min 50mg daily < 30 ml/min 25mg daily 2.5 or 5 mg tablets daily 2.5 mg CrCl < 50 and on a 3A4 (clarithromycin inhibitor, rifampin inducer) 5 mg daily no adjustment for renal or hepatic impairment Dosing in trials 25 to 400 mg daily Weight neutral Pregnancy category: B ~$250 for 1 month Side Effects Sore throat Diarrhea URI UTI Headache Rare Pancreatitis Combo with pioglitazone Oseni

14 GLP-1 Agonists SQ Injections Dosing Comments Exenatide (Byetta ) Exenatide LAR (Bydureon ) Liraglutide (Victoza ) 5mcg, 10 mcg BID 30 min prior to meal Contraindicated CrCl <30 ml/min or ESRD Approved for use with Lantus Insulin Extend DOA due to microspheres Dosage is 2mg every 7 days without regard to meals Supplied as a powder that must be reconstituted & given immediately Boxed warning for thyroid C-cell tumors Doses include 0.6mg, 1.2mg, 1.8mg QD Administered daily by a pre-filled multi-dose pen independent of meals Start with lowest dose and titrate as needed in weekly increments Boxed warning for thyroid C-cell tumors Only drug class with significant weight loss results (3 to 5 lbs) Side Effects Nausea, Vomiting, Diarrhea, Constipation Pregnancy-class C Contraindicated in type 1 DM, DKA, severe GI disease, pancreatitis, gallstones, alcoholism, high TG kidney transplant VERY expensive

15 Comparison of Characteristics of Incretin Based Therapy GLP-1 Agonist DPP-4 Inhibitors Effect on A1c % % Insulin secretion Glucagon suppression Slowing of gastric emptying yes Marginal Effect on weight Weight loss Weight neutral Common Side Effects Nausea, Vomiting, Diarrhea Headache, Sinusitis, Rhinorrhea Administration Injection Oral Hypoglycemia with monotherapy No No

16 Sodium Glucose Transport Inhibitors

17 New Oral Diabetes Therapies Sodium Glucose Co-Transporter (SGLT2 ) dapaglifozin (Forxiga) and canaglifozin (Invokana) Induces glycosuria and lowers glucose Blocks reabsorption of glucose in the kidney, increasing glucose excretion and lowering blood glucose levels Side Effects: Dehydration Polyuria Frequent UTI Female genital mycosis

18 Glucose-lowering Effects of Medications Treatment A1c % Change in FPG mg/dl Change in PPG mg/dl Insulin secretor Metformin Glitazones (TZDs) Carbohydrate blocker GLP-1 agonist DPP-4 Inhibitors Insulin unlimited unlimited unlimited Insulin secretor + metformin Insulin secretor + TZDs DPP-4 Inhibitor + metformin DPP-4 Inh. + TZDs

19 Insulin Products Type of Insulin Onset Peak Duration Rapid-Acting Lispro (Humalog) Aspart (Novolog) Glulisine (Apidra) Short Acting Regular min min 3-5 hrs min 1.5-2hrs 5-12hrs Intermediate NPH 1-2 hrs 4-8 hrs hrs Long-Acting Glargine (Lantus) 1-2 hrs No peak 24 hrs Detemir (Levemir) 1-2 hrs Relatively flat hrs

20 Other Insulins NovoLIN 70/30 NovoLOG Mix 70/30 Humalog Mix 75/25 Novolin 50/50 U500 Regular Insulin

21 Short Acting Insulin: Humulin/Novolin R- Regular Quick onset Clear Can be given subcutaneously or intravenously Dosing Usually before meals Administer prior to meals due to onset Used to mix with intermediate acting insulin Okay for insulin pumps

22 Rapid Acting Insulin: Novolog/Humalog/Apidra Quick onset and duration Take 5-10 minutes before meal or right after meal Typically three times daily with meals Very quick onset, short duration Can be mixed with NPH Can be used in insulin pumps Pens or vials

23 Intermediate Acting Insulin: Humulin/Novolin N- NPH Intermediate acting Typical dosing: twice daily Sometimes can see three times a day, especially if on tube feeds In combination with short or rapid acting Cloudy If mixing, clear before cloudy Vials

24 Long Acting Insulin: Lantus/Levemir Duration: Lantus: up to 24 hours Levemir: hours Dosing: Lantus: usually once daily, sometimes twice daily Levemir: usually twice daily Do not mix Usually in combination with rapid-acting Pens or vials

25 Combination Insulin Humulin or Novolin 70/30 Humalog 75/25 Mix Novolog 70/30 Mix Benefits Baseline/meal insulin in one dose Easier to draw up dose with syringe Decreases number injections Less cost Problems Fixed dose combination Difficult to adjust individual insulins

26 U-500 Insulin Concentrated insulin that is 5 times stronger than U- 100 (common strength) Each 1 ml = 500 units of insulin Available in a 20 ml vial only Dose may be administered using traditional insulin syringe (units) or tuberculin syringe (ml) Should not be given intravenously (IV)

27 Why Use Concentrated Insulin? Insulin resistant patients require high doses of insulin Doses greater than 200 units per day qualify patients for U- 500 insulin Volume limitation with subcutaneous injections 1 milliliter (ml) = 100 units per syringe Glucose response is better with the administration of smaller volumes of insulin

28 Treatment Strategies

30 Endogenous Insulin

31 Common Insulin Regimens: Basal only

32 Common Insulin Regimens: Basal-Bolus

33 Common Insulin Regimens: Split-Mix

34 Medicaid Preferred Drug List

35 Oral Therapies

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39 Injectable Therapies

40 Preferred Insulins

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42 Prevention of Complications

43 Hypertension BP measured at each visit Goal: SBP <140mm Hg Treatment: Lifestyle modifications Medication should include ACEi or ARB If > 1 medication, administer at bedtime

44 Hyperlipidemia Annual fasting lipid panel Goal LDL: No CVD: <100mg/dL CVD: <70mg/dL, with high-dose statin is option Primarily statin therapy

45 Aspirin Primary Prevention: ASA (75-162mg/d) Increased CV risk (10 year risk of >10%) Secondary Prevention: DM and h/o CVD ASA (75-162mg/d)

46 Smoking Cessation Routine part of diabetes care Use of cessation products Heightened risk of CVD, premature death, increased rate of microvascular complications

47 Nephropathy and Retinopathy Optimal BG and BP control Annual assessment for albuminuria and renal function Dilated eye exam at time of diagnosis, then every two years

48 Neuropathy Screening at diagnosis and then annually Routine foot care Monofilament testing Proper foot, nail and skin care Footwear **Avoid diabetic foot ulcer infections

49 In Conclusion.

50 Summary A1c goal <7.0% Metformin is first-line, but may need additional medications A1c >10%, insulin may be necessary Lifestyle modifications, including diet and exercise Screening to prevent microvascular and macrovascular complications ADHERENCE

51 Diabetes Medications Minal Patel, PharmD, BCPS