Effective Use of Insulin in Diabetes: Update for 2007 Thomas M. Flood, MD Director Georgia Center for Diabetes Atlanta, Georgia

Key Question ? How comfortable are you with initiating insulin therapy in your patient population? Completely comfortable Somewhat comfortable Slightly comfortable Not comfortable at all Use your keypad to vote now!

Faculty Disclosure Dr Flood has no relevant financial relationships with any commercial interests to disclose.

Learning Objectives State current management goals for diabetes Identify barriers to optimal use of insulin, and how to overcome them Discuss the roles of short-, intermediate-, and long-acting insulins in the management of diabetes

A1C Targets Suggested by Different Organizations Optimal target: A1C <6% (normal range) Organization A1C Target (%) AACE <6.5 EASD ADA <7 (general) <6* (individual patient) *As close to normal (<6%) without significant hypoglycemia. AACE = American Association of Clinical Endocrinologists; ADA = American Diabetes Association; EASD = European Association for the Study of Diabetes.

? Key Question What percentage of patients with diabetes achieve the AACE goal of A1C <6.5%? 25% 35% 55% 75% Use your keypad to vote now!

National average = 67% above goal (A1C 6.5%) State of Diabetes in America: Blood Sugar Control Across the United States as Measured by A1C National average = 67% above goal (A1C 6.5%) WA 68.4 ME 27.2 MT 55.2 ND 29.7 MN 59.3 OR 64.2 VT VT = 26.7 NH = 20.4 MA = 29.5 CT = 28.4 RI = 29.5 NJ = 67.3 DE = 66.4 MD = 68.1 ID 63.3 NY 71.1 NH SD 24.6 W 24.2I WY 63.0 MI 65.4 MA CT RI IA 58.9 PA 70.9 NE 56.5 NV 67.3 OH 71.7 NJ IL 72.6 IN 66.4 MD UT 72.4 CO 67.1 WV 69.5 DE CA 34.5 VA 67.7 KS 67.0 MO 66.2 KY 66.8 TN 65.6 NC 65.7 OK 65.6 AZ 67.3 AR 69.6 NM 68.6 SC 66.3 MS 72.8 AL 71.3 GA 69.3 TX 67.7 LA 71.3 FL 63.9 N >157,000 Top 10 Highest AACE. State of Diabetes in America. May 2005. Available at: http://www.aace.com/public/awareness/stateofdiabetes/DiabetesAmericaReport.pdf American Association of Clinical Endocrinologists. State of Diabetes in America. Report presented at: American Association of Clinical Endocrinologists 14th Annual Meeting and Clinical Congress; Washington, DC; May 18, 2005. http://www.aace.com/public/awareness/stateofdiabetes/DiabetesAmericaReport.pdf.

Diabetes Demographics in the United States Population Aged ≥20 Years Physician-Diagnosed Diabetes (%) Undiagnosed Diabetes (%) 1998-1994 2001-2004 Male 5.4 7.6 3.5 4.3 Female 7.1 2.6 1.8 White 5.0 6.2 2.8 Black 8.6 11.4 4.2 3.1 Mexican 9.7 11.8 4.7 3.3 Total 7.3 3.0 Adapted from: National Center for Health Statistics. Health, United States, 2006. With Chartbook on Trends in the Health of Americans. Hyattsville, Md: 2006.

No A1C Threshold in Type 2 Diabetes Epidemiologic Data From the UKPDS 80 Myocardial infarction Microvascular end points 60 AACE Goal Adjusted Incidence per 1000 Person-Years (%) 40 20 ? 5 6 7 8 9 10 11 Updated Mean A1C (%) UKPDS = United Kingdom Prospective Diabetes Study. Stratton IM et al. BMJ. 2000;321:405-412.

Risk Factor Control in Adults With Diabetes: NHANES III (1988-1994)/NHANES 1999-2000 NHANES 1999-2000, n = 370 48.2% 50 44.3% P <.001 37.0% 40 35.8% 33.9% 29.0% 30 Patients (%) 20 10 5.2% 7.3% A1C <7% BP <130/80 mm Hg TC <200 mg/dL Good control* *Achieved all 3 indicated goals. BP = blood pressure; NHANES = National Health and Nutrition Examination Survey; TC = total cholesterol. Saydah SH et al. JAMA. 2004;291:335-342.

Stages of Type 2 Diabetes: Criteria for Advancing to Next Stage? A1C not at target: 7.0% 100 Monotherapy 75 Combination oral therapy β-Cell Function (% β) 50 Insulin 25 Type 2 Diabetes Phase I Type 2 Diabetes Phase II Phase III -12 -10 -6 -2 2 6 10 14 Years From Diagnosis Based on data of UKPDS 16. UKPDS Group. Diabetes. 1995;44:1249-1258.

Stepwise Management of Type 2 Diabetes + Diet and exercise + Oral monotherapy + Oral combination + Oral combo + insulin + Insulin Biggest Clinical Hurdle? Adapted from Williams G. Lancet. 1994;343:95-100.

? Key Question What is the approximate amount that A1C can be lowered through use of oral agents? 1% 2% 3% 4% Use your keypad to vote now!

Oral Antihyperglycemic Monotherapy Maximum Therapeutic Effect on A1C Acarbose Insulin -0.5 -1.0 -1.5 -2.0 Nateglinide Reduction in A1C (%) Glipizide GITS Glimepiride Repaglinide Pioglitazone Metformin Rosiglitazone Sitagliptin Precose [PI]. West Haven, Conn: Bayer; 2003; Aronoff S et al. Diabetes Care. 2000;23:1605-1611; Garber AJ et al. Am J Med. 1997;102:491-497; Goldberg RB et al. Diabetes Care. 1996;19:849-856; Hanefeld M et al. Diabetes Care. 2000;23:202-207; Lebovitz HE et al. J Clin Endocrinol Metab. 2001;86:280-288; Simonson DC et al. Diabetes Care. 1997;20:597-606; Wolfenbuttel BH, van Haeften TW. Drugs. 1995;50:263-288.

UKPDS: Early Initiation of Insulin Therapy Improves A1C Control Conventional therapy Insulin therapy Sulfonylurea ± insulin therapy 9 8 7 A1C (%) ULN = 6.2% 6 5 1 2 3 4 5 6 Years From Randomization ULN = upper limit of A1C nondiabetic range. Wright A et al. Diabetes Care. 2002;25:330-336.

Clinical Inertia: “Failure to Advance Therapy When Required” Last A1C Value Before Abandoning Treatment 10 9.6% Mean A1C at Last Visit (%) 9.1% 9 8.6% 8.8% 8 ADA Goal 7 Sulfonylurea Diet/Exercise Combination Metformin 2.5 Years 2.9 Years 2.2 Years 2.8 Years Brown JB et al. Diabetes Care. 2004;27:1535-1540.

? Key Question What are the barriers for your patients with type 2 diabetes regarding initiation of insulin therapy? Concern that insulin use is “forever” Fear of injection Equating insulin use with worsening diabetes and complications Fear of weight gain Use your keypad to vote now!

Patient Barriers to Insulin Use: Perception vs Reality Failing oral therapy 58% of patients believe using insulin means they have failed OAD therapy OAD failure is due to progressive nature of type 2 diabetes; insulin is best agent to control disease Needle phobia Fear associated with early experiences Current needles considered painless; easy-to-use injection systems are available Fear of complications Common association of insulin with diabetic complications Complications are due to uncontrolled, progressive disease; insulin actually results in reduction of vascular damage OAD = oral antidiabetic drug. Meese J. Diabetes Educ. 2006;32:9S-18S; Peyrot M et al. Diabet Med. 2005;22:1379-1385.

Clinician Barriers to Insulin Use: Perception vs Reality Hypoglycemia is prevalent with insulin use Severe hypoglycemia is very uncommon in patients with type 2 diabetes, occurring at 10% the rate in patients with type 1 diabetes Insulin use increases atherosclerosis Studies indicate no exacerbation of cardiovascular disease There is weight gain with insulin use Weight gain is modest and can be controlled with diet and exercise Patients have a negative attitude regarding insulin use Insulin is a “positive” approach to achieving glycemic control Douek IF et al. Diabet Med. 2005;22:634-640; Malmberg K et al. J Am Coll Cardiol. 1995;26:57-65; Malmberg K et al. BMJ. 1997;314:1512-1515; Romano G et al. Diabetes. 1997;46:1601-1606; UKPDS Group. Lancet. 1998;352:837-853.

Information and Patient Education Links for Healthcare Professionals American Association of Diabetes Educators (www.diabeteseducator.org) American Association of Clinical Endocrinologists (www.aace.com) American Diabetes Association (www.diabetes.org) International Diabetes Federation (www.idf.org) National Diabetes Education Initiative (www.ndei.org) National Diabetes Education Program (ndep.nih.gov) National Institute of Diabetes and Digestive and Kidney Diseases (www2.niddk.nih.gov)

Next Steps… What do we do for the patient who has failed on 1 or 2 oral agents?

Basal Insulin Therapy Usual first step when beginning insulin therapy Continue OAD and add basal insulin to optimize FPG A1C of up to 9.0% often brought to goal by addition of basal insulin therapy to OADs Easy and safe: patient-directed treatment algorithms with small risk of serious hypoglycemia ADA and EASD recommended: “Although 3 OADs can be used, initiation and intensification of insulin therapy is preferred based on effectiveness and expense” Basal Insulin Therapy The addition of basal insulin therapy to oral antidiabetic drugs (OADs) is the usual first step in transitioning from OAD therapy. The goal is to optimize fasting plasma glucose (FPG) values and reduce glucolipotoxicity. In many cases, A1C levels of up to 9.0% can often be brought to goal using basal insulin therapy. There are several patient-directed treatment algorithms available, which make titration to effective doses easy for the patient to manage. There is a small risk of hypoglycemia associated with basal insulin therapy. References American Diabetes Association. Standards of medical care in diabetes. Diabetes Care. 2006;29(suppl 1): S4-S42. American Association of Clinical Endocrinologists. Implementation Conference for ACE Outpatient Diabetes Mellitus Consensus Conference recommendations: Position statement. Available at: http://www.aace.com/pub/pdf/guidelines/OutpatientImplementationPositionStatement.pdf. Accessed July 3, 2006. Category: Insulin Therapy Keywords: basal, FPG, A1C, initiate, goals, insulin FPG = fasting plasma glucose. ADA. Diabetes Care. 2006:29(suppl 1):S4-S42; AACE position statement. Available at: http://www.aace.com/pub/pdf/guidelines/OutpatientImplementationPositionStatement.pdf. Nathan DM et al. Diabetes Care. 2006;29:1963-1972.

Rationale for Basal Insulin Therapy: Insulin and Glucose Patterns Normal T2DM Glucose Insulin 400 120 100 300 80 μU/mL mg/dL 200 60 40 100 20 6:00 10:00 14:00 18:00 22:00 2:00 6:00 6:00 10:00 14:00 18:00 22:00 2:00 6:00 B L D B L D Time Time B = breakfast; D = dinner; L = lunch; T2DM = type 2 diabetes mellitus. Polonsky KS et al. N Engl J Med. 1988;318:1231-1239.

Options for Initiating Insulin Therapy Basal insulin NPH insulin (at bedtime) Insulin detemir (once or twice daily) Insulin glargine (once daily) Premixed insulin preparations 70/30 NPH insulin/regular insulin 50/50 NPL insulin/insulin lispro 70/30 NPA insulin/insulin aspart 75/25 NPL insulin/insulin lispro Analog premixes NPA = neutral protamine aspart; NPL = neutral protamine lispro.

Idealized Profiles of Human Insulin and Basal Insulin Analogs NPH Plasma Insulin Levels Detemir Glargine 0:00 2:00 4:00 6:00 8:00 10:00 12:00 14:00 16:00 18:00 20:00 22:00 24:00 Time Plank J et al. Diabetes Care. 2005;28:1107-1112; Rave K et al. Diabetes Care. 2005;28:1077-1082; Rosenstock J, Goldstein BJ, et al, eds. Textbook of Type 2 Diabetes. London, UK, and New York, NY: Martin Dunitz; 2003:131-154.

Twice-Daily Split-Mixed Regimens or Lispro Mix (75/25)–Aspart Mix (70/30) 4:00 16:00 20:00 24:00 Breakfast Lunch Dinner Insulin Action 8:00 12:00 Time Glucose levels Insulin levels Adapted with permission from Leahy J. In: Leahy J, Cefalu W, eds. Insulin Therapy. New York: Marcel Dekker; 2002:87; Nathan DM. N Engl J Med. 2002;347:1342-1349.

Open-Label, Twice-Daily Exenatide vs Once-Daily Insulin Glargine: Self-Monitoring Blood Glucose Profiles (n = 549) Exenatide 5 μg bid 1st 4 weeks, then 10 μg bid Insulin Glargine 10 U/d, titrated to target FPG <100 mg/dL 240 240 220 220 200 200 Mean end of study dose was 25 U compared with 47 U in the Treat-to-Target trial. Least-squares mean (SE) data for self-monitored blood glucose concentrations at baseline and week 26 are shown for the exenatide and insulin glargine groups. In a 24-hour period, data were collected just before each meal (fasting, pre–midday meal, pre– evening meal), 2 hours after each meal (post–morning meal, post–midday meal, post– evening meal), and at 3:00 a.m. At week 26, the exenatide group had higher mean values for blood glucose levels at fasting (P <0.001), before lunch (P = 0.023), before dinner (P = 0.006), and at 3:00 a.m. (P <0.001), but the group had lower glucose levels after morning (P <0.001) and evening (P <0.001) meals than the group receiving insulin glargine. Heine RJ et al. Ann Intern Med. 2005;143:559-569. 180 180 Blood Glucose (mg/dL) 160 160 140 140 120 Baseline (week 0) 120 Baseline (week 0) Endpoint (week 26) 100 100 Endpoint (week 26) Prebreakfast Prelunch Predinner 3 AM Prebreakfast Prelunch Predinner 3 AM Both medications lowered A1C from 8.2% to 7.1% from baseline Weight change: exenatide –2.3 kg, glargine +1.8 kg Nausea: exenatide 57.1%, glargine 8.6% Heine RJ et al. Ann Intern Med. 2005;143:559-569.

Steps in Transition From Basal to Basal-Bolus Insulin Therapy in T2DM Glargine, Detemir, or NPH HS Weekly titration based on FPG All oral agents continued STEP 1 Above target Add insulin Main meal STEP 2 Above target Add insulin Next largest meal STEP 3 Above target Add insulin Last meal STEP 4 Above target: A1C >7.0% FPG >110 mg/dL A1C <7.0%, FPG <110 mg/dL HS = at bedtime. Adapted with permission from Karl DM. Curr Diab Rep. 2004;4:352-357.

Case Study

Case Study: Initiating Insulin Therapy 60-year-old man: 10-year history of T2DM and hypertension Current T2DM medications: metformin 1000 mg bid, rosiglitazone 8 mg AM, and glimepiride 8 mg qd Hypertension medications: 40 mg lisinopril, 10 mg amlodipine, 12.5 mg HCTZ Dyslipidemia medication: 10 mg atorvastatin Physical exam: weight = 245 lb (10-lb increase); height = 6’0”; BMI = 34.2 kg/m2; waist circumference = 44 in; BP = 130/80 mm Hg Laboratory: TC = 167 mg/dL; TG = 206 mg/dL; HDL = 35 mg/dL; LDL = 90 mg/dL A1C = 8.9%; plasma glucose in the office = 198 mg/dL Creatinine 1.1 mg/dL, normal LFTs HCTZ = hydrochlorothiazide; TG = triglycerides; HDL = high-density lipoprotein; LFTs = liver function tests; BMI = body mass index.

Case Study (cont’d) Patient agrees to basal insulin therapy, however: Expresses feelings of failure at inability to control glycemia with OADs Displays anxiety about injections You explain the progressive nature of diabetes: Convey that insulin injections are the best way to achieve glycemic control Describe injection options (“painless” needles, injector pens, etc) Indicate that you and the patient will be a “team” in getting to the A1C goal

? Decision Point Which insulin would you use? NPH at bedtime Glargine once daily Twice-daily premixed Detemir at bedtime Use your keypad to vote now!

Treat-to-Target Trial: Oral Agents + Glargine or NPH at Bedtime Patients (n = 756) with inadequate glycemic control (A1C >7.5%) taking 1 or 2 oral agents Started with 10 U/d bedtime basal insulin and adjusted weekly to target FPG 100 mg/dL: Mean self-monitored FPG values from preceding 2 days (mg/dL) Increase of insulin dosage (U/d) ≥180 8 140 – 180 6 120 – 140 4 100 – 120 2 Exceptions were no increase in dosage if plasma-referenced glucose <72 mg/dl was documented at any time in the preceding week, and in addition to no increase, small insulin dose decreases (2 – 4 units/day per adjustment) were allowed if severe hypoglycemia (requiring assistance) or plasma-referenced glucose <56 mg/dl were documented in the preceding week.1 1Riddle MC et al. Diabetes Care. 2003;26:3080-3086. Hermansen K et al. Diabetes Care. 2006;29:1269-1274; Riddle MC et al. Diabetes Care. 2003;26:3080-3086.

Treat-to-Target Trial: Oral Agents + Glargine or NPH at Bedtime (n=756): Efficacy Results Patients (n=756) with inadequate glycemic control (A1C >7.5%) on 1 or 2 oral agents Randomized to bedtime glargine or NPH Target FPG 100 mg/dL Adjustments made once weekly; therapy is advanced unless hypoglycemia present *In both groups, FPG decreased from 194 or 198 mg/dL to 117 or 130 mg/dL, respectively, by study end, and A1C decreased from 8.6% to 6.9% by 18 weeks. Riddle MC et al. Diabetes Care. 2003;26:3080-3086.

Treat-to-Target Trial: Timing and Frequency of Hypoglycemia Hypoglycemia by Time of Day Basal insulin Insulin glargine 350 * * NPH insulin 300 * 250 * Hypoglycemia Episodes (PG 72 mg/dL) 200 * * * 150 100 50 B L D 20:00 22:00 24:00 2:00 4:00 6:00 8:00 10:00 12:00 14:00 16:00 18:00 20:00 Time *P <.05 (between treatment). Riddle MC et al. Diabetes Care. 2003;26:3080-3086.

Detemir vs NPH Insulin in T2DM (n = 476) 400 350 300 250 200 150 100 50 A1C (%) 10.0 9.0 8.0 7.0 6.0 Detemir NPH Hypoglycemia Events* -2 4 8 12 16 20 24 2 4 8 12 16 20 24 Study Week Study Week *All reported events, including symptoms only. Hermansen K et al. Diabetes Care. 2006;29:1269-1274.

Case Study (cont’d) 10 U glargine is added to OADs Patient is sent home with the “2, 4, 6, 8 algorithm” with a target FPG goal of 100 to 110 mg/dL.1 Similar algorithm can be used with detemir2 FPG (mg/dL)  Insulin Dose (U/d) 120-140 2 140-160 4 160-180 6 >180 8 Alternative strategy: increase basal insulin dose by 2 units every 3 days until FPG 100 mg/dL*3 *Certain populations (children, pregnant women, and the elderly) require special considerations. Riddle MC et al. Diabetes Care. 2003;26:3080-3086. Hermansen K et al. Diabetes Care. 2006;29:1259-1271. Davies M et al. Diabetes. 2004;53(suppl 2):1980.

Case Study (cont’d) Patient is seen 1 month later FPG still above 200 mg/dL, using up to 30 U daily Patient is frustrated and feels the insulin does not work

? Decision Point What do you do now? Keep increasing the insulin dose Go to twice-daily premixed Switch to exenatide Send patient for gastric bypass consult Use your keypad to vote now!

Treat-to-Target Trial 50 Units 45 Total Daily Dose (U) 42 40 37 33 28 30 21 20 10 10 1 2 3 4 5 6 7 8 10 12 15 18 21 N = 756. Riddle MC et al. Diabetes Care. 2003;26:3080-3086. Weeks in Study

Case Study (cont’d) Patient is taking 75 U with FPG controlled (<100 mg/dL to rarely >110 mg/dL) since last visit 4 months ago Patient’s last A1C = 6.9%, monitoring occasional postprandial blood sugars Patient finds insulin injections painless and after speaking with you, feels that he is now a partner in his therapy program

Case Study (cont’d) Over the next 3 years, patient seen for routine follow-up every 3 to 4 months Remains medically stable, with A1C values 6.5% to 7.2% 3.25 years after adding basal insulin glargine, A1C has increased to 8.2%, however, FPG checks remain <120 mg/dL

? Decision Point What do you do now? Increase glargine Switch to twice-daily premixed Switch to 4-shot basal-bolus program Increase monitoring to AC and HS, and have patient report after 2 weeks Use your keypad to vote now! AC = before meals; HS = at bedtime.

Case Study (cont’d) Because the patient’s FPGs are good and post-prandial glucose levels are high, the decision is made to switch to twice-daily premixed insulin The patient is encouraged to increase daily monitoring to adjust insulin dose

At Lower A1C Levels, PPG Contributes More to Overall A1C Than FPG Contribution (%) 1 2 3 4 5 A1C Quintile PPG = postprandial glucose. Reprinted with permission from Monnier L et al. Diabetes Care. 2003;26:881-885.

Plasma Glucose (mg/dL) Prandial Excursions Are Evident, Especially Around a Single Key Meal: Insulin Glargine vs Premixed (n = 209) 350 300 250 200 150 100 50 Premixed† Glargine Baseline Plasma Glucose (mg/dL) * * * * * Week 28 BB B90 BL L90 BD D90 Bed 3 AM Time of Day Total units = 51.3 ± 26.7 with glargine plus OADs vs 78.5 ± 39.5 with premixed insulin (BIAsp 70/30) *Denotes statistically significant difference between treatment groups at specific times. †Premixed = BIAsp 70/30. Raskin P et al. Diabetes Care. 2005;28:260-265.

Case Study (cont’d) Daily Blood Glucose Diary 147 110 153 185 57 138 Week Ending March 24 Breakfast Lunch Dinner MS Middle of Night Dose Blood Sugar Monday 147 110 153 185 57 Tuesday 138 112 170 164 48 Wednesday 140 90 155 205  Thursday 166 105 134 213 60 Friday Saturday Sunday

Twice-Daily Split-Mixed Regimens or Lispro Mix (75/25)–Aspart Mix (70/30) 4:00 16:00 20:00 24:00 Breakfast Lunch Dinner Insulin Action 8:00 12:00 Time Glucose levels Insulin levels Adapted with permission from Leahy J. In: Leahy J, Cefalu W, eds. Insulin Therapy. New York: Marcel Dekker; 2002:87; Nathan DM. N Engl J Med. 2002;347:1342-1349.

Idealized Profiles: Rapid-Acting Insulin Analogs Inhaled insulin* Regular insulin Plasma Insulin Levels 0:00 2:00 4:00 6:00 8:00 10:00 12:00 14:00 16:00 18:00 20:00 22:00 24:00 Time *Inhaled dry human insulin (Exubera®) powder Rosenstock J, Goldstein BJ, et al, eds. Textbook of Type 2 Diabetes. London, UK, and New York, NY: Martin Dunitz; 2003:131-154; Plank J et al. Diabetes Care. 2005; 28:1107-1112; Rave K et al. Diabetes Care. 2005;28:1077-1082.

Case Study (cont’d) Decision is made to switch to basal-prandial therapy to reduce hypoglycemia and postprandial highs 60% of patient’s total daily insulin dose is given as basal insulin – 54 U glargine qhs titrated to FPG 100-110 mg/dL Before the main meal, a rapid-acting analog is added: glulisine, initiated at 5 units, up-titrated using a treat-to-target algorithm Patient continues to self-monitor glucose

Meal Insulin: Rapid-Acting Analogs (Lispro, Aspart, Glulisine) vs Regular Analog insulin 10 Timing of food absorbed 8 RHI 6 Insulin Activity 4 2 1 2 3 4 5 6 7 8 9 10 11 12 Hours RHI = regular human insulin. Adapted with permission from Howey DC et al. Diabetes. 1994;43:396-402.

Advantages of Rapid-Acting Analogs Short duration of action—fewer between-meal “hypos” than regular insulin Flexible mealtime dosing More consistent kinetics Day to day Across anatomical sites With large doses Slightly faster onset of glulisine action (compared to lispro) in obese and morbidly obese subjects (independent of BMI)* Adapted from Hirsch IB. N Engl J Med. 2005;352:174-183. Becker RHA et al. Exp Clin Endocrinol Diabetes. 2005;113:435-443. *Heise T et al. Diabetes. 2005;54(suppl 1):A145.

? Decision Point The best time to use a rapid-acting insulin analog is: Before a meal After a meal Either works well Use your keypad to vote now!

Significant reduction in A1C with pre- and postmeal glulisine Pre- and Postmeal Efficacy of Insulin Glulisine vs Regular Human Insulin Significant reduction in A1C with pre- and postmeal glulisine P <.05 P <.05 P <.05 Baseline Endpoint Efficacy of Algorithmic Basal-Prandial Insulin Analog Titration At week 24, the A1C was significantly reduced in both the ALG and Carb Count groups (P<0.0001). Reference Bergenstal R, Johnson M, Powers M, Wynne A, Vlajnic A, Hollander A. Using a simple algorithm (ALG) to adjust mealtime glulisine (GLU) based on preprandial glucose patterns is a safe and effective alternative to carbohydrate counting (Carb Count). Diabetes. 2006;55(suppl 1):A105.Abstract 441P. Significant A1C reduction with premeal glulisine compared to premeal human insulin Garg SK et al. Endocr Pract. 2005;11:11-17; Garg SK et al. Poster presented at ADA 64th Annual Scientific Sessions, June 4-8, 2004, Diabetes. 7:529P.

Case Study (cont’d) At 6-month follow-up patient is doing well with 70 U glargine and 10 U to 17 U glulisine at supper Actual dose adjusted by Meal carbohydrate content Activity Insulin supplement of additional 1 U for every 25 mg/dL above 130 mg/dL (prandial glucose) A1C = 6.3% He feels well, has infrequent “hypos,” and is pleased with his blood glucose control

Q & A

PCE Takeaways

PCE Takeaways: Basal-Prandial Insulin Replacement An effective insulin treatment strategy provides both basal and postprandial insulin coverage Initially, prandial insulin may be needed only at the largest meal of the day, with coverage at other meals added based on prandial glucose levels Rapid-acting insulin analogs closely match normal mealtime insulin patterns Prandial Insulin Replacement: Summary An effective strategy for the treatment of patients with type 2 diabetes is the use of an insulin regimen that provides both basal and postprandial insulin coverage. Initially, prandial insulin may be needed only at the largest meal of the day. Over time, premeal glucose levels may indicate the need for administration of prandial insulin at more meals. Rapid-acting insulin analogs, which closely match normal mealtime insulin patterns compared with regular human insulin, are an effective option. A simple algorithm based on premeal blood glucose levels can been shown to be a safe and effective way to titrate prandial insulin doses.

Key Question ? How much more comfortable do you now feel you will be initiating insulin therapy in your patient population? Much more comfortable Somewhat comfortable Slightly comfortable Not comfortable at all Use your keypad to vote now!