Prediabetes: You Can Help Your Patients Exit the Express Lane to Diabetes! Jaini Patel, PharmD, BCACP Assistant Professor of Pharmacy Practice Midwestern University Chicago College of Pharmacy Kathleen Vest, PharmD, CDE, BCACP Associate Professor of Pharmacy Practice Midwestern University Chicago College of Pharmacy Disclosures/Conflict of Interest The speakers declare no conflicts of interest, real or apparent, and no financial interests in any company, product or service mentioned in this program, including grants, employment, gifts, stock holdings and honoraria. Objectives Pharmacists At the conclusion of this program, the pharmacist will be able to: Objectives Pharmacy Technicians At the conclusion of this program, the pharmacy technician will be able to: Demonstrate familiarity current guideline recommendations for patients with prediabetes or increased risk of diabetes Review published data for non- pharmacologic as well pharmacologic interventions in patients with prediabetes Apply evidence- based recommendations to patient case scenarios for prevention of diabetes Identify patients at increased risk of diabetes List medications used in the treatment of obesity and prediabetes Discuss ways that patients can prevent progression from prediabetes to diabetes Prediabetes Prediabetes Hyperglycemia below the threshold for diagnosis of Diabetes Mellitus (DM) 37% of the U.S. population (51% of which are >65yo) 29.1 million with DM; 86 million with prediabetes Parameters that denote prediabetes: Impaired Fasting Glucose (IFG):100-125mg/dl Impaired Glucose Tolerance (IGT): 140-190mg/dl 2 hours post 75g oral glucose load A1C 5.7% 6.4% (per ADA) Ideal to evaluate all 3 components to identify risk for DM 5 CDC National Diabetes Fact Sheet, United States, 2014. ADA. Diabetes Care. 2014;37(1):S16. 1
IFG vs IGT IFG: Predominant hepatic insulin resistance Normal skeletal muscle insulin sensitivity Early phase insulin release is impaired Plasma glucose rises during first 60 minutes of oral glucose tolerance test (OGTT) IGT: Normal to slightly reduced hepatic insulin resistance Predominant skeletal muscle insulin resistance Early & late phase insulin release is impaired Plasma glucose continues to rise even after 60 minutes of OGTT In the fast lane Over many years & at different rates Up to 70% individuals with prediabetes eventually progress into diabetes state By 2050, 1 in 3 adults in the U.S. could have diabetes if this trend continues Associated with increased prevalence of microvascular and macrovascular damage Nathan DM, et al. Diabetes Care. 2007 Mar;30(3):753 759. Portero McLellan KC et al. Practical Diabetology.2014;33(2):6-11. CDC.National Diabetes Fact Sheet, United States, 2011. Risk Factors BMI 25 kg/m 2 ( 23 kg/m2 for Asian American patients) Physical inactivity First degree relative with type 2 diabetes mellitus High risk race/ethnicity (African American, Latino, Native American, Asian American, Pacific Islander) HTN ( 140/90mmHg or on therapy for hypertension) HDL <35 mg/dl (0.90 mmol/l) and/or triglycerides >250 mg/dl (2.82 mmol/l) HbA1C 5.7%, IFG, and/or IGT on previous testing History of CVD Absence of above criteria but age 45 or older Women with PCOS Women who delivered a baby weighing >9 lbs Women who were diagnosed with gestational diabetes 2013 Obesity Guidelines BMI (in any category) Risk of Diabetes ADA. Diabetes Care. 2014;37(1):S16. http://circ.ahajournals.org/content/early/2013/11/11/01.cir.0000437739.71477.ee. Accessed 7/2/15 Goals of Prevention Delay onset of diabetes Preserve beta cell function Prevent underlying state of insulin resistance Prevent or delay microvascular and macrovascular complications Patient Case You are a pharmacist working in a physician s office. AG is a 45 yo Hispanic male who presents for his first clinic visit. PMH: Hyperlipidemia GERD Sleep Apnea (uses CPAP) Current Medications: Atorvastatin 10mg daily at bedtime Lansoprazole 30mg daily in morning 2
Patient Case: AG Family History: Mother: hypertension, heart disorder, deceased at age 65 Father: diabetes, hypertension Brother: diabetes, hyperlipidemia Social History: Former smoker; quit 4/2013; smoked 1ppd X 15 years Diet: per patient he eats junk Exercise: none BP: 130/80 mm/hg Pulse: 88 Question # 1 Based on AG s risk factors, what would be your initial step? a. Continue present management b. Check A1C, FPG, and 2- h 75g OGTT c. Check A1C, complete metabolic panel, and lipid panel d. Start Vitamin D supplementation Weight: 288 lbs BMI: 39.35 kg/m 2 Labs: available to review from 2009; unremarkable A1C: 6.1% Lipids (mg/dl): TC: 177, TG: 72, HDL 53, LDL: 110 CMP: FPG: 100 mg/dl SCr: 0.93, BUN: 15 AST: 21, ALT: 27 Electrolytes wnl Patient Case: Lab Results ADA Recommendations Non Pharmacologic Interventions Target weight loss of 7% of body weight Increase physical activity to at least 150 min/week of moderate activity Follow Up is extremely vital for success of non- pharmacologic measures Pharmacologic Interventions Metformin may be considered; especially in those with BMI > 35 kg/m 2, aged <60 yo, and women with prior GDM Data for other pharmacological agents (Acarbose, Orlistat, and TZDs) are mentioned but no specific recommendation Follow Up Annual monitoring for development of diabetes Screening and treatment of modifiable risk factors for CVD (obesity, DL, HTN, smoking, etc.) ADA. Diabetes Care. 2014;37(1):S20. AACE Recommendations Nonpharmacologic Interventions Primary goal: Weight loss Therapeutic Lifestyle Changes (TLC): diet + exercise Bariatric Surgery for BMI > 35: lap band; gastric sleeve, gastric bypass Pharmacologic Interventions Weight loss: phentermine, orlistat, lorcaserin, phentermine/topiramate ER Antihyperglycemics: Metformin, Acarbose first line TZDs, GLP- 1 agonists use these if absolutely necessary; with caution CVD Risk Modification: antihypertensives, lipid lowering agents Question # 2 Given AG s lab results for A1c and FPG, per ADA guidelines, what would be the most appropriate to do at this time? a. Refer patient to a dietitian to modify dietary habits, promote weight loss, and encourage increasing physical activity b. Start Metformin c. Recheck labs in 3 years d. A & B AACE. Comprehensive Diabetes Management. 2013;19(2):10-11 3
Evidence- based Lifestyle Interventions What is the evidence for prevention of diabetes? Diabetes Prevention Program (DPP) (2002) Landmark study on prevention of diabetes in individuals with IFG and IGT Compared placebo + standard lifestyle, intensive lifestyle intervention, and Metformin 850mg bid + standard lifestyle groups over an average of 2.8 years follow up 58% reduced incidence of DM in intensive lifestyle intervention group vs 31% in Metformin group compared to placebo Knowler, WC, et al. N Engl J Med. 2002;346:393-403 DPP Intensive Lifestyle Intervention Goals: At least 7% weight loss 150 minutes physical activity/week Key features: 1. Frequent contact between participants and lifestyle coaches 2. A structured, state- of- the- art, 16- session core- curriculum (handout) 3. Supervised physical activity sessions and motivational campaigns 4. Individualization through a toolbox of adherence strategies and tailoring to address ethnic diversity 5. An extensive network of training, feedback, and clinical support. Evidence- based Lifestyle Interventions Da Qing IGT & Diabetes Study (1997) Treatment arms: diet only, exercise only, and diet + exercise Patients with IGT followed up at 2 years interval 46% risk reduction in diet + exercise group over 6 years Finnish Diabetes Prevention Study (2001) Treatment arms: Intensive lifestyle and control group with general lifestyle modification counseling Recruited patients with IGT 58% risk reduction in incidence of DM in intervention group over 4 years. Knowler, WC, et al. N Engl J Med. 2002;346:393-403 Plan XR, et al. Diabetes Care. 1997;20:537-544. Tuomilehto J, et al. N Engl J Med. 2001;344:1343-1350 Evidence- based Pharmacotherapy Biguanides: Metformin (Glucophage ) Alpha- glucosidase inhibitor (AGIs): Acarbose (Precose ), Voglibose * Thiazolidinediones (TZDs): Pioglitazone (Actos ), Rosiglitazone (Avandia ), Troglitazone Dipeptidyle peptidase- IV (DPP- 4) inhibitors: Vildagliptin * Insulin: Glargine (Lantus ) GLP- 1 receptor agonists: Liraglutide (Victoza ), Exenatide (Byetta ) Weight loss agents: Orlistat (Xenical ) Phentermine/topiramate (Qysmia ) * Agents not available in U.S. Market Oral Diabetic Agents Biguanides AGIs TZDs ( glitazones ) Metformin Acarbose Pio Rosi Tro Study DPP, IDPP STOP- NIDDM ACT- NOW DREAM TRIPOD Dose Duration 850mg bid (DPP) 250mg bid (IDPP) 2.8 yrs (DPP) 2.5 yrs (IDPP) 100mg TID 45mg daily 8mg daily + lifestyle modification 400mg daily 3.3 yrs 3.75 yrs 3 yrs 2.5 yrs Population IFG &/or IGT IGT IGT IFG &/or IGT Women with Gestational DM in Wt 2.1 kg (DPP) - - - - - - - - - - - - - DM incidence 31% (DPP) 14% (IDPP) effective in FPG > 110, Age < 60 yrs, & BMI > 35 kg/m 2 25% 72% 60% 55% 91% RRR in MI 34% RRR in HTN 25% d/c d due to GI ADRs risk Bladder cancer MI risk of hepato - toxicity (withdrawl 2000) Net Harm >> Net Benefit Fluid retention, weight gain, HF, fracture Knowler, WC, et al. N Engl J Med. 2002;346:393-403. Chiasson JL, et al. Lancet. 2002;359(9323):2072-2077. DeFronzo RA, et al. N Engl J Med. 2011;364(12):1104. Gerstein HC, et al. Lancet. 2006;368(9541):1096. Buchanan TA, et al. Diabetes. 2002;51(9):2796 4
Injectable Diabetic Agents Insulin GLP- 1 agonists Glargine Exenatide Liraglutide Study ORIGIN Exenatide for Weight Loss Study Obesity Study Dose PM dose 10mcg bid 1.8-3 mg/day Duration 6 years 6 months 5 months Population IGT or IFG Obese patients - NGT, IGT, or IFG Obese patients without DM in Weight - - - 5.1+0.5kg 4.8-7.2 kg DM incidence 28% 77% 84-96% of wt gain, hypoglycemia Sustained weight loss at 2 years Sustained weight loss at 2 years Question # 3 Based on evidence- based guideline recommendations, what would you recommend for pharmacotherapy option for AG? a. Glargine b. Acarbose c. Metformin d. Pioglitazone Gerstein HC, et al. N Engl J Med. 2012;367(4):319. Astrup, A, et al. Lancet 2009;374:1606-16. Rosenstock, J, et al. Diabetes Care 2010;33(6) 1173-1175 2013 Obesity Guidelines 2013 AHA/ACC/TOS Guideline for the Management of Overweight and Obesity in Adults A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and The Obesity Society Endorsed by the American Association of Cardiovascular and Pulmonary Rehabilitation, American Pharmacists Association, American Society for Nutrition, American Society for Preventive Cardiology, American Society of Hypertension, Association of Black Cardiologists, National Lipid Association, Preventive Cardiovascular Nurses Association, The Endocrine Society, and WomenHeart: The National Coalition for Women with Heart Disease Main Points Who to Assess for Weight Loss: YES BMI >30 or BMI 25<30 with additional risk factor(s): Weight loss treatment is indicated for Obese individuals Overweight individuals with 1 or more indicators of increased CVD risk (e.g., diabetes, prediabetes, hypertension, dyslipidemia, elevated waist circumference) or other obesity related comorbidities. Intensive management of CVD risk factors or other obesity- related medical conditions (e.g., sleep apnea) should be instituted, regardless of weight loss efforts. http://circ.ahajournals.org/content/early/2013/11/11/01.cir.0000437739.71477.ee Accessed 7/2/15 Main Points Weight Loss and Risk of Diabetes In overweight and obese adults at risk for type 2 diabetes, average weight losses of 2.5 kg to 5.5 kg at 2 years, achieved with lifestyle intervention (with or without orlistat) reduces the risk of developing type 2 diabetes by 30% to 60%. Strength of the Evidence: High 2013 Obesity Guidelines: Bariatric Surgery and DM Risk At 10 years, incidence and prevalence of type 2 diabetes are lower in those who have undergone surgery. Strength of the Evidence: Low Adults with BMI 30 who underwent various bariatric surgeries achieved the following after 2-3 years: Mean weight loss 20-35% fasting glucose incidence of type 2 DM Strength of the Evidence: High http://circ.ahajournals.org/content/early/2013/11/11/01.cir.0000437739.71477.ee Accessed 7/2/15 http://circ.ahajournals.org/content/early/2013/11/11/01.cir.0000437739.71477.ee Accessed 7/2/15 5
Weight Loss Agents Orlistat Phentermine/Topiramate Study XENDOS 1 CONQUER/SEQUEL 2 Dose 120mg TID + lifestyle modification 7.5/46 mg or 15/92 mg daily Duration 4 years 1-2 years Population Obese patients - NGT or IGT BMI of 27-45 kg/m 2 & >2 comorbidities in Wt 5.8 kg 8-10 kg DM incidence 37.3% 54% (7.5/46mg dose) 76% (15/92mg dose) GI ADRs; absence of long- term durability Many ADRs; REMS enrollment advised 1. Torgerson et al. Diabetes Care. 2004:(27(1):155-161 2.Gavey et al. Am J Clin Nutr. 2012;95(2): 297-308 Weight Loss Agents Lorcaserin (Belviq ) Bupropion/ Naltrexone (Contrave ) Liraglutide (Saxenda ) Study BLOOM- DM 1 COR- Diabetes 2 Kim et al 3 Dose 10mg twice daily 360mg/32mg 0.6-1.8mg SQ daily + lifestyle modification Duration 52 weeks 56 weeks 14 weeks Population Obese + Type 2 DM BMI >27kg/m 2 + Type 2 DM BMI 27-40 kg/m 2 in Wt >5% >5% in 44.5% of pts 6.8kg DM incidence A1C 0.9% A1C 0.6% Normal fasting glucose in 75% pts Risk of serotonin syndrome? GI- related ADRs HR 2-3 bpm, despite wt loss 1. O Neil et al. Obesity (Silver Spring). 2012;20(7):1426-1436 2. Smith et al. Diabetes Obes Metab. 2013;15(9): 863-866 3.Kim et al. Diabetes Care 2013;36:3276-3282 Question # 4 With lifestyle recommendations, AG has lost 5lbs in the past 3 months. At this time, AG s physician asks you to recommend a medication for weight loss. Which of the following medications would be most appropriate for AG at this time? a. Orlistat b. Phentermine/Topiramate c. Lorcaserin d. Liraglutide e. Either a or b Weight Loss Agents: Patient Education Medications should only be used as an adjunct Lifestyle changes are required! activity and calories This may require you to spend extra time with the patient Medication efficacy is limited to 5-10% in successful patients Obesity is considered a chronic disease and it s treatment is a life- long process Clinical Pearls Educate! Create Awareness! Support Diabetes Prevention Programs (DPPs) http://www.idph.state.il.us/diabetes/ Recognize patients with risk factors for prediabetes impending progression to diabetes and perform testing Monitor prediabetes parameters every 3 years if normal High risk patients with normal test results should be strongly advised to incorporate lifestyle modifications early on to prevent or delay onset of prediabetes/diabetes Consider Metformin for obese patients <60 years of age Are you ready to help your patients exit the fast lane to Diabetes and help curve the epidemic? 6
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