THE PHARMACIST S ROLE IN MANAGING PATIENTS WITH ADVANCED TYPE 2 DIABETES

FACULTY INFORMATION THE PHARMACIST S ROLE IN MANAGING PATIENTS WITH ADVANCED TYPE 2 DIABETES Presenter: Jennifer Costello, PharmD, BCPS, BC-ADM Ambulatory Care Clinical Pharmacist Internal Medicine Faculty Practice Saint Barnabas Medical Center Livingston, New Jersey Jennifer Costello, PharmD, BCPS, BC-ADM Ambulatory Care Clinical Pharmacist Internal Medicine Faculty Practice Saint Barnabas Medical Center Livingston, NJ Moderator: Elena Beyzarov, PharmD Director of Scientific Affairs Pharmacy Times Office of Continuing Professional Education Plainsboro, New Jersey DISCLOSURES Jennifer Costello, PharmD, BCPS, BC-ADM, has no financial relationships with commercial interests to disclose. Pharmacy Times Office of Continuing Professional Education Planning Staff Judy V. Lum, MPA, Elena Beyzarov, PharmD, and Donna W. Fausak have no financial relationships with commercial interests to disclose. PTOCPE uses an anonymous peer reviewer as part of content validation and conflict resolution. The peer reviewer has no relevant financial relationships with commercial interests to disclose. The contents of this webinar may include information regarding the use of products that may be inconsistent with or outside the approved labeling for these products in the United States. Pharmacists should note that the use of these products outside current approved labeling is considered experimental and are advised to consult prescribing information for these products. Please send all questions or comments concerning this webinar to: CEINFO@pharmacytimes.com. Or You can call 800-597-6372 and leave a message. All emails and messages will be answered within 48-hours in the order that they are received. EDUCATIONAL OBJECTIVES Explore prevalence and pathophysiology, as well as clinical and economic burden related to type 2 diabetes and resultant complications Examine evolving standards of care in type 2 diabetes, including treatment goals that extend beyond A1c to include other essential clinical metrics (eg, A1c, blood pressure, lipid levels) Discuss current management of type 2 diabetes, including updated clinical practice guidelines and incorporation of new therapeutic classes into practice recommendations Develop strategies that address clinical inertia and other barriers to optimal management of type 2 diabetes THE PHARMACIST S ROLE IN MANAGING PATIENTS WITH ADVANCED TYPE 2 DIABETES Jennifer Costello, PharmD, BCPS, BC-ADM Ambulatory Care Clinical Pharmacist Internal Medicine Faculty Practice Saint Barnabas Medical Center Livingston, NJ 1

PREVALENCE, PATHOPHYSIOLOGY, AND ECONOMIC BURDEN OF TYPE 2 DIABETES MELLITUS (T2DM) US PREVALENCE OF DIABETES In 2010 25.8 million people diagnosed with T2DM 8.3% of entire population In children, up to 45% of newly diagnosed cases T2DM, with majority overweight or obese Centers for Disease Control and Prevention. National diabetes fact sheet: national estimates and general information on diabetes and prediabetes in the United States, 2011. Atlanta, GA: US Department of Health and Human Services, Centers for Disease Control and Prevention; 2011. ECONOMIC BURDEN OF DIABETES Annual economic burden associated with diagnosed diabetes in United States estimated to be $174 billion ~ $1 in every $10 healthcare attributed to diabetes FUTURE PREDICTION FOR DIABETES If current trend continues, it is estimated that 1 in every 3 people will be diagnosed with diabetes by year 2050 Dall, TM, Edge Mann, S, Zhang Y, et al. Distinguishing the economic costs associated with type 1 and type 2 diabetes. Population Health Management. 2009 ;12(2):103-110. Boyle J, Thompson T, Gregg E, et al. Projection of the year 2050 burden of diabetes in the US adult population: dynamic modeling of incidence, mortality, and prediabetes prevalence. Population Health Metrics. 2010;8:29. NATURAL HISTORY OF T2 DM Impaired glucose tolerance Undiagnosed diabetes Known diabetes COMPLICATIONS FROM DIABETES Microvascular Kidney disease Macrovascular Peripheral arterial disease (PAD) Insulin resistance Insulin secretion Postprandial glucose Fasting glucose Blindness and eye problems Nervous system disease/neuropathy Heart disease Stroke Microvascular complications Macrovascular complications Adapted from Ramlo-Halsted BA, Edelman SV. Prim Care. 1999;26:771-789. Dental disease Centers for Disease Control and Prevention. National diabetes fact sheet: national estimates and general information on diabetes and prediabetes in the United States, 2011. Atlanta, GA: US Department of Health and Human Services, Centers for Disease Control and Prevention; 2011. 2

TEACHABLE MOMENTS: GOALS Generally, every 1% point drop in A1C can reduce risk of microvascular complications by 40% Blood pressure control reduces risk of cardiovascular disease (heart disease or stroke) among people with diabetes by 33% to 50% Improved control of LDL cholesterol can reduce cardiovascular complications by 20% to 50% In patients with prediabetes, losing 7% of body weight can delay and possibly prevent the disease HEDIS/NCQA INFORMATION Percentage of T2DM patients meeting following goal parameters 2007 2008 2009 2010 A1c <7% 30.5% 31.1% 35.4% 35.1% LDL <100 30.6% 33.3% 41.1% 43.6% BP <130/80 31% 31.8% 30.2% BP <140/80 59% 60.6% 56.2% 59.2% Centers for Disease Control and Prevention. National diabetes fact sheet: national estimates and general information on diabetes and prediabetes in the United States, 2011. Atlanta, GA: US Department of Health and Human Services, Centers for Disease Control and Prevention; 2011. The Healthcare Effectiveness Data and Information Set (HEDIS) Continuous Improvement and the Expansion of Quality Measurement. THE STATE OF HEALTH CARE QUALITY 2011. National Committee for Quality Assurance. GUIDELINES TREATMENT GOALS FOR ADULTS WITH DIABETES American Diabetes Association (ADA) A1c: <7% Preprandial: 70-130 mg/dl American Association of Clinical Endocrinologists (AACE) A1c: 6.5% Preprandial: <110 mg/dl 2-hr Postprandial: <180 mg/dl 2-hr Postprandial: <140 mg/dl Blood Pressure <140 / 80 mm Hg LDL <100 mg/dl; HDL >50 mg/dl, Triglycerides <150 mg/dl Smoking Cessation AACE Diabetes Care Plan Guidelines. Endocr Pract. 2011;17(suppl 2). American Diabetes Association. Standards of Medical Care in Diabetes Mellitus 2012. Diabetes Care. 2012;35(suppl ):11-63. A1C: GERIATRIC CONSIDERATIONS Intensive glucose control (A1c <6.5%) has been linked to increased all-cause and cardiovascular mortality and hypoglycemia in elderly patients with T2DM How "tightly" to control geriatric patient's blood glucose needs to be individualized, based on: Patient's functional and cognitive status How well hypoglycemic symptoms are recognized How to respond to them and other disease states 1.American Diabetes Association. Standards of Medical Care in Diabetes Mellitus -- 2012, Diabetes Care. 2012;35(suppl ):11-63. 2. Brown AF, Mangione CM, Saliba D, Sarkisian CA; California Healthcare Foundation/American Geriatrics Society Panel on Improving Care for Elders with Diabetes. Guidelines for improving the care of the older person with diabetes mellitus. J Am Geriatr Soc. 2003;51(suppl ):S265 S280. A1C: GERIATRIC CONSIDERATIONS A1c <8% is acceptable for frail elderly patients With duration of illness >10 years With comorbid conditions requiring combination medications For elderly patients with T2DM who are relatively healthy, attaining target goals for the following may be more important than normalized glycemic control Blood pressure Lipids Smoking cessation Diet and exercise 1. American Diabetes Association. Standards of Medical Care in Diabetes Mellitus -- 2012, Diabetes Care. 2012;35(Suppl ):11-63. 2. Brown AF, Mangione CM, Saliba D, Sarkisian CA; California Healthcare Foundation/American Geriatrics Society Panel on Improving Care for Elders with Diabetes. Guidelines for improving the care of the older person with diabetes mellitus. J Am Geriatr Soc. 2003;51(Suppl Guidelines):S265 S280. 3

Antihyperglycemic therapy in type 2 diabetes: general recommendations. Principles of the AACE Algorithm for the Treatment of Type 2 DM Copyright 2012 American Diabetes Association, Inc. Inzucchi SE et al. Diabetes Care. 2012;35:1364-1379. OVERVIEW OF GUIDELINES DIFFERENCES ADA Last updated 2012 Metformin first-line drug Dual or triple therapy may be considered; however, many patients ultimately need insulin monotherapy or in combination with other medications AACE Last updated 2013 Metformin preferred first-line drug; however, other classes also used as monotherapy Dual or triple therapy preferred over insulin monotherapy or in combination with other medications ADA OVERVIEW OF GUIDELINES DIFFERENCES DPP-4 inhibitors not included in 2009 because effectiveness on glycemic control lower than or equivalent to other agents and cost; now can use, but patient should be close to A1c goal GLP-1 receptor agonists considered second-line agents AACE Favors use of GLP-1 receptor agonists and DPP-4 inhibitors with higher priority because of effectiveness and safety profiles DIABETES MEDICATION TIMELINE PHARMACOTHERAPY Insulin 1922 SUs 1957 Metformin Alpha-glucosidase inhibitor 1995 Symlin Sitagliptin Saxagliptin Linagliptin Alogliptin (Pramlintide) (Januvia) (Onglyza) (Tradjenta) (Nesina ) Amylinomimetic 2005 DPP-4 2006 DPP-4 2009 DPP-4 2011 DPP-4 2013 1960 1995 2000 2005 2010 2012 2013 Meglitinides Thiazolidinediones 1997 Exenatide (Byetta) GLP-1 2005 Liraglutide (Victoza) GLP-1 2010 Extended Exenatide (Bydureon) GLP-1 2012 New Class Approval 2013 1. Philippe J, Raccah D. Int J Clin Pract. 2009;63(2):321-332. 2. Patlak M. Breakthroughs in Bioscience. 2002. http://www.faseb.org/portals/0/pdfs/opa/diabetes.pdf. 4

Targeted Sites of Diabetes Drug Classes Liver Biguanides TZDs Pancreas Hepatic glucose overproduction Glucose absorption issues Biguanides Sulfonylureas Meglitinides DDP-4 inhibitors GLP-1 receptor agonists Plasma Glucose Gut Alpha-glucosidase inhibitors DPP-4 Inhibitors GLP-1 receptor agonists Beta-cell dysfunction Buse JB. Williams Textbook of Endocrinology:10 th ed; Philadelphia, PA; WB Saunders; 2003:1427-1483. Muscle & Fat Insulin Resistance Biguanides TZDs DEFINITION OF INCRETINS Incretins are intestinal hormones released in response to meals; regulate insulin release. Creutzfeldt. Diabetologia. 1985;28:5645. In cret in Intestine Secretion Insulin INCRETIN PHYSIOLOGY GLP-1 (Glucagon-like peptide 1) Increases glucose-dependent insulin secretion from beta cells Decreases inappropriate glucagon secretion from alpha cells Increases B-cell growth and replication Slows gastric emptying and reduces food intake Degraded by DPP-4 enzyme Meal GIP (Glucose-dependent insulinotropic polypeptide) Increases glucose-dependent insulin release Degraded by DPP-4 enzyme 1. Drucker DJ, Nauck MA. Lancet. 2006;368:1696-1705. 2. Nauck MA. Am J Med. 2009;122(uppl 1):S3-S10. Drawn in Inkscape by Ilmari Karonen based on w:image:incretins and DPP 4 inhibitors.jpg from http://casesblog.blogspot.com/2006/11/dpp-4-inhibitors-for-treatment-of.html. GLP-1: EXENATIDE Exenatide: Analog of hormone incretin GLP-1 Hormone derived from saliva of Gila monster, poisonous lizard found in Southwestern US and Mexico Clinical Effect Immediate-release exenatide decreases A1c ~ 0.7% to 1% Extended-release exenatide decreases A1c 1.5% to 1.9% GLP-1 EXENATIDE Dose Immediate-release: Initial: 5 mcg twice daily SQ, within 60 minutes prior to a meal; after 1 month, may be increased to 10 mcg twice daily pen available Extended-release: 2 mg SQ once weekly vial only Combination therapy considerations Reduce dose of sulfonylureas when adding GLP-1 agents to therapy No changes to therapy if adding with metformin No dose adjustments in hepatic or renal dysfunction limited experience 1. Byetta [package insert]. San Diego, CA: Amylin Pharmaceuticals, Inc. 2005;2008. 2. Bydureon [package insert]. San Diego, CA: Amylin Pharmaceuticals, Inc. 2012. 1. Byetta [package insert]. San Diego, CA: Amylin Pharmaceuticals, Inc. 2005;2008. 2. Bydureon [package insert]. San Diego, CA: Amylin Pharmaceuticals, Inc. 2012. 5

COMBINATION THERAPY: Exenatide and Insulin FDA approved exenatide as add-on therapy with insulin glargine, diet, and exercise for adult patients Exenatide group had 1.7% decrease in A1c levels, vs 1% drop in insulin-alone group (P <0.001) Body weight in patients receiving exenatide lower by 4 lb (avg) vs 2 lb increase in insulin-alone group Reductions in A1c in exenatide patients not associated with increase in hypoglycemia compared with insulin-alone group Buse JB, Bergenstal RM, Glass LC, et al. Use of twice-daily exenatide in basal insulin-treated patients with type 2 diabetes: A randomized, controlled trial. Ann Intern Med. 2011;154:103-112. GLP-1: LIRAGLUTIDE Synthetic long-acting analog of human GLP-1 Clinical Effect: Liraglutide decreases A1c by ~ 1% Dosage: SQ: Initial: 0.6 mg once daily for 1 week; then increase to 1.2 mg once daily May increase to 1.8 mg once daily if optimal glycemic response not achieved with 1.2 mg/day Available as pen No dose adjustments in hepatic or renal dysfunction limited experience Victoza [package insert]: Novo Nordisk. Princeton, NJ; 2010. COMBINATION OF LIRAGLUTIDE AND INSULIN DETEMIR Addition of insulin detemir to liraglutide and metformin helped decrease A1c by additional 0.5% after 1 year of therapy (P < 0.0001) Minor hypoglycemia seen in 0.228 episodes/year among patients on combination of insulin, liraglutide, and metformin There were no adverse events that resulted in subject discontinuation from the study EXENATIDE ONCE WEEKLY VERSUS LIRAGLUTIDE ONCE DAILY IN PATIENTS WITH T2DM (DURATION-6) 26-week, open-label, randomized, parallel-group study at 105 sites in 19 countries in patients with T2DM Figure shows both drugs associated with a clinically important decrease in A1c from baseline. *P <0.0001; P =0.0005; P = 0.0012; P = 0.0018. Change in A1c (primary endpoint) was not significantly different in patients taking liraglutide than in those taking exenatide Morrow L, Hompesch M, Guthrie H, et al. Diabetes Obes Metab.. 2011;13(1):75-80. doi: 10.1111/j.1463-326.2010.01322. Buse, JB, Nauck M, Forst T, et al. Lancet. 2013;12;381(9861):117-124 PHARMACIST COUNSELING POINTS WITH GLP- 1 AGONISTS Due to effects on gastric emptying, these agents may reduce rate and extent of absorption of orally administered drugs Administer medications 1 hour prior to use of immediaterelease exenatide or liraglutide Use with caution in patients receiving medications with narrow therapeutic window or those requiring rapid absorption from GI tract Postmarketing reports of increased INR; caution with concomitant use of warfarin and exenatide Immediate release exenatide only: Time of administration 60 minutes prior to meal PHARMACIST COUNSELING POINTS WITH EXENETIDE ER Exenetide ER Will likely affect drug absorption; use with caution Requires approximately 2 weeks of therapy before full effect Patient may see glucose elevations during this time Counseling point on missing doses If you miss a dose of BYDUREON, take it as soon as you remember, as long as the next dose is due at least three days later If you miss a dose and the next regularly scheduled dose is due one or two days later, do not take the missed dose but take BYDUREON on the next regularly scheduled day. Byetta [package insert]. San Diego, CA: Amylin Pharmaceuticals, Inc. 2005;2008. Bydureon [package insert]. San Diego, CA: Amylin Pharmaceuticals, Inc. 2012. Victoza [package insert]: Novo Nordisk. Princeton, NJ; 2010. Bydureon [package insert]. San Diego, CA: Amylin Pharmaceuticals, Inc. 2012. 6

GLP-1 AGONIST SIDE EFFECTS Thyroid tumors: US Black Box Warning Dose- and duration-dependent thyroid C-cell tumors developed in animal studies with GLP-1 therapy; relevance in humans unknown During clinical studies, 5 cases of thyroid C-cell hyperplasia reported in rats Patients should be counseled on risk and symptoms (eg, neck mass, dysphagia, dyspnea, persistent hoarseness) of thyroid tumors Contraindicated in patients with or family history of medullary thyroid cancer (MTC) and in patients with multiple endocrine neoplasia syndrome type 2 (MEN2) GLP-1 AGONIST SIDE EFFECTS (CONT.) Pancreatitis Exenatide: 30 reports of acute pancreatitis and 6 reports of hemorrhagic or necrotizing pancreatitis 2 deaths, 4 recovered Conclusive evidence linking pancreatitis to liraglutide therapy not established Discontinue drug if pancreatitis suspected Symptoms such as pain in abdomen that is severe, will not go away. Pain that may happen with or without vomiting. Pain that is felt going from your abdomen through your back Do NOT re-challenge if pancreatitis diagnosed Bydureon [package insert]. San Diego, CA: Amylin Pharmaceuticals, Inc. 2012. Byetta [package insert]. San Diego, CA: Amylin Pharmaceuticals, Inc. 2005;2008 Victoza [package insert]: Novo Nordisk. Princeton, NJ; 2010. Bydureon [package insert]. San Diego, CA: Amylin Pharmaceuticals, Inc. 2012. Byetta [package insert]. San Diego, CA: Amylin Pharmaceuticals, Inc. 2005;2008 Victoza [package insert]: Novo Nordisk. Princeton, NJ; 2010. COMPARISON OF DPP-4 INHIBITORS DIPEPTIDYL PEPTIDASE-IV (DPP-4) INHIBITORS Drug Name Dosage Clinical Efficacy Metabolism/Excretion Sitagliptin 100 mg once daily *must be renally adjusted 0.6-0.8% A1c reduction Saxagliptin 2.5-5 mg once daily 0.4-0.6% A1c reduction Linagliptin 5 mg once daily 0.4-0.7% A1c reduction Renal elimination many studies evaluating use in renal dysfunction Hepatic/Renal Excretion if giving concomitant with strong CYP3A4 inhibitors or patients with Scr <50ml/min give 2.5 mg once daily Hepatic use with caution with CYP3A4 inhibitors Alogliptin *Available in summer 2013 25 mg once daily 0.4-0.6% A1c reduction Renal elimination requires renal dose reduction 1. Januvia [package insert]: Merck. Whitehouse Station, NJ; 2007 2. Onglyza [package insert]: Bristol-Myers Squibb. Princeton, NJ; 2011 3. Tradjenta [package insert]. Ridgefield, CT: Boehringer Ingelheim Pharmaceuticals, Inc; 2011 4. Nesina [package insert]. Deerfield, IL: Tekeda Pharmaceutical Compay; 2013 DPP-4 INHIBITOR CLASS SIDE EFFECTS Hypersensitivity reactions: Rare hypersensitivity reactions Anaphylaxis, angioedema, Stevens-Johnson syndrome, reported in postmarketing surveillance Reports with both sitagliptin, saxagliptin and alogliptin No reports associated with linagliptin Discontinue if signs/symptoms of hypersensitivity reactions occur Events generally noted within first 3 months of therapy, and may occur with initial dose 1. Januvia [package insert]: Merck. Whitehouse Station, NJ; 2007 2. Onglyza [package insert]: Bristol-Myers Squibb. Princeton, NJ; 2011 3. Tradjenta [package insert]. Ridgefield, CT: Boehringer Ingelheim Pharmaceuticals, Inc; 2011 4. Nesina [package insert]. Deerfield, IL: Tekeda Pharmaceutical Compay; 2013 DPP-4 INHIBITOR CLASS SIDE EFFECTS (CONT.) Pancreatitis: Sitagliptin: Reported cases of acute pancreatitis (including hemorrhagic and necrotizing pancreatitis with some fatalities) Linagliptin: Pancreatitis reported in 8 of 4687 patients while being treated with linagliptin compared with 0 of 1183 patients treated with placebo Monitor for signs/symptoms of pancreatitis Discontinue use immediately if pancreatitis suspected Alogliptin reports post-marketing cases of pancreatitis Saxagliptin: None reported but thought to be potential class effect 1. Januvia [package insert]: Merck. Whitehouse Station, NJ; 2007 2. Onglyza [package insert]: Bristol-Myers Squibb. Princeton, NJ; 2011 3. Tradjenta [package insert]. Ridgefield, CT: Boehringer Ingelheim Pharmaceuticals, Inc; 2011 4. Nesina [package insert]. Deerfield, IL: Tekeda Pharmaceutical Compay; 2013 7

DPP-4 INHIBITOR PHARMACIST COUNSELING POINTS Combination therapy considerations: Can continue current metformin dosage Reduce dose of sulfonylureas recommended Reduce dose of insulin recommended Dose reductions should be made in patients with renal dysfunction: Sitagliptin Saxagliptin Alogliptin Caution with concomitant use with strong CYP3A4 inhibitors: Saxagliptin Linagliptin FUTURE THERAPIES: SODIUM-GLUCOSE CO-TRANSPORTER-2 (SGLT2) INHIBITORS 1. Januvia [package insert]: Merck. Whitehouse Station, NJ; 2007 2. Onglyza [package insert]: Bristol-Myers Squibb. Princeton, NJ; 2011 3. Tradjenta [package insert]. Ridgefield, CT: Boehringer Ingelheim Pharmaceuticals, Inc; 2011 4. Nesina [package insert]. Deerfield, IL: Tekeda Pharmaceutical Compay; 2013 FUTURE THERAPIES: SODIUM-GLUCOSE CO-TRANSPORTER-2 (SGLT2) INHIBITORS Renal Handling of Glucose, Non-Diabetic Individual SGLT2 is a low-affinity, high-capacity transporter requiring 1 glucose and 1 sodium molecule. SGLT2 in the kidney plays a critical role in the reabsorption of glucose. It is almost exclusively found in the S1 segment of the proximal renal tubule; accounts for ~ 90% of the renal reabsorption of glucose (180 grams of glucose/day) Breakdown: blocks reabsorption of glucose by the kidney and increases excretion of glucose in urine S1 part of proximal tubule Glucose filtered/day = 180 g Reabsorption Glucose SGLT2 ~90% ~10% S G L T 1 Virtually all the glucose filtered is reabsorbed and glucose does not appear in the urine. Collecting duct S3 part of proximal tubule SGLT, Sodium-glucose cotransporter NO GLUCOSE Neumiller JJ, White JR, Jr, Campbell RK. Sodium-glucose co-transport inhibitors: progress and therapeutic potential in type 2 diabetes mellitus. Drugs. 2010;70:377 385 Wright EM. Am J Physiol Renal Physiol. 2001;280:F10-F18. Thorens B. Am J Physiol. 1996;270:G541-G553. SODIUM-GLUCOSE CO-TRANSPORTER-2 (SGLT2) INHIBITORS First drug in class, dapagliflozin, rejected by FDA in January 2012 Concerned drug raised risk of bladder and breast cancer in 11 phase III clinical trials Second drug, canagliflozin (Invokana) received FDA approval on March 29, 2013 A third SGLT2 inhibitor, ipragliflozin (Astellas Pharma) has been filed for marketing approval in Japan, and a fourth, empagliflozin (Eli Lilly/Boehringer Ingelheim), is in phase 3 trials and has just been filed for approval in the United States. Canagliflozin (Invokana) 26-week, randomized, double-blind, placebo-controlled, phase 3 trial 584 adult subjects with T2DM received canagliflozin 100 or 300 mg or placebo once daily. At week 26, canagliflozin 100 and 300 mg (compared with placebo) significantly reduced A1C from baseline, ( 0.77, 1.03 and 0.14%, respectively; p<0.001 for both). Adverse events The incidence of genital mycotic infections was higher with canagliflozin compared with placebo There incidence of urinary tract infections was higher with canagliflozin compared with placebo The percentage of subjects with documented hypoglycaemia was similar with canagliflozin 100 and 300 mg and placebo (3.6, 3.0 and 2.6%, respectively), with no report of severe hypoglycaemia. FDA Rejects Dapagliflozin for Type 2 Diabetes By Emily P. Walker, Washington Correspondent, MedPage Today Hardman TC, Dubrey SW. Development and Potential Role of Type-2 Sodium-Glucose Transporter Inhibitors for Management of Type 2 Diabetes. Diabetes Therapy (2011) 2(3):133-145. Stenlöf K, Cefalu WT, Kim KA, et al. Efficacy and safety of canagliflozin monotherapy in subjects with type 2 diabetes mellitus inadequately controlled with diet and exercise. Diabetes Obes Metab. 2013;15(4):372-382. 8

CLINICAL INERTIA Defined as failure to intensify treatment of a patient who is not at evidence-based A1c goal Clinical inertia postulated as major barrier to better diabetes care Concern of clinical inertia focusing too closely on sole glucose control; may divert attention from other diabetes quality measures such as blood pressure and LDL control All healthcare providers should be aware of clinical inertia and focus on optimizing all patient outcomes PRINCIPLES OF COMBINATION THERAPY SELECTION Early vs late disease How much A1c lowering needed? Patients with frequent hypoglycemia events? Intolerable side effects Safety profiles Too costly? Insurance coverage? Nonadherence to multiple self-monitoring blood glucose values Ease of use Frequency Injectable vs noninjectable Berlowitz DR, Ash AS, Glickman M, Friedman RH, Pogach L, Nelson AL. Developing a Quality of Measure for Clinical Inertia in Diabetes Care Health Services Research doi: 10.1111/j.1475-6773.2005.00436.x. 2005. available online at http://http://www.blackwell.synergy.com.htm. Nathan DM et al. Diabetes Care. 2009; 32:193 203. PATIENT CASE # 1 JP is a 62-year-old female with an 2-year history of T2DM. Current A1c = 7.4% Serum creatinine = 1.1 mg/dl; CrCl = 65 ml/min - Body mass index = 30 Current DM therapy includes: Metformin ER 2000 mg daily and Glipizide 20 mg XL daily Question: What changes should be made to DS s T2DM therapy? A) Continue with current therapy and lifestyle changes B) Add sitagliptin (DPP-4) and reduce dose of glipizide C) Add exenatide (GLP-1) and reduce dose of glipizide D) Add basal insulin and discontinue glipizide TACTICS TO IMPROVE PATIENT ADHERENCE Find that teachable moment : Explain how medication would benefit patient Explain goals of diabetes control Explain how patients are in control of their outcomes Identify barriers to adherence: Do patients need to demonstrate injection technique? Are patients concerned about side effects? Is it too expensive? Are they spreading out their supply Encourage, Motivate, Encourage Questions THANK YOU 9