Inpatient Management of Hyperglycemia Guillermo Umpierrez, MD, CDE Saturday, February 10, :30 a.m. 11:15 a.m.

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1 Inpatient Management of Hyperglycemia Guillermo Umpierrez, MD, CDE Saturday, February 1, 218 1:3 a.m. 11:15 a.m. There are over 7.5 million hospital admissions for patients with diabetes in the US. About 2 to 3% of patients have prior history of diabetes. The prevalence of hyperglycemia is even higher and reported in 38% of patients in community hospitals, 41% of critically ill patients with acute coronary syndromes, and in 8% of patients after cardiac surgery. Diabetes imposes a substantial economic burden on society. The total estimated cost of diagnosed diabetes in 212 in the US was $245 billion, of which $76 billion (41%) represented inpatient medical care. Extensive data from observational and randomized controlled trials indicate that inpatient hyperglycemia, in patients with or without a prior diagnosis of diabetes, is associated with an increased risk of complications and mortality. It is also well established that improvement in glucose control with goal-directed insulin regimens reduces hospital complications and mortality in critically ill, as well as in general medicine and surgery patients. Recent studies and meta-analyses have shown that intensive insulin therapy is associated with increased risk of hypoglycemia, which has been independently associated with increased morbidity and mortality in hospitalized patients. In patients with adequate oral intake, the basal bolus approach is the preferred regimen as it addresses the three components of insulin requirement: basal, nutritional, and correctional doses. The use of basal-bolus insulin had greater improvement in blood glucose control than sliding scale alone. In general surgery patients, the basal bolus regimen resulted in significant improvement in glucose control and in a reduction in the frequency of the composite of postoperative complications including wound infection, pneumonia, respiratory failure, acute renal failure and bacteremia. In patients with reduced total caloric intake due to lack of appetite, acute illness, medical procedures or surgical interventions, the Basal Plus trial in patients with type 2 diabetes compared a standard basal bolus regimen with glargine once daily and glulisine before meals and a single daily dose of glargine and supplemental doses of glulisine for correction of hyperglycemia (>14 mg/dl) per sliding scale. There was similar improvement in glycemic control and in the frequency of hypoglycemia with Basal Plus regimen compared to basal bolus regimen. The use of oral antidiabetic agents is generally not recommended in hospitalized patients due to the limited data available on their safety and efficacy. The safety and efficacy of sitagliptin, a DPP-4 inhibitor, for the management of inpatient hyperglycemia was recently evaluated in 3 randomized controlled studies in general medicine and surgery hospitalized patients with type 2 diabetes. These studies indicate that in patients with mild to moderate hyperglycemia (BG < 2 mg/dl), there was no difference in the mean BG concentration or in the occurrence of hospital complications. Transition to an outpatient setting requires planning and coordination. Although insulin is used for most patients with diabetes in the hospital, many patients do not require insulin after discharge. Patients with acceptable diabetes control could be discharged on their pre-hospitalization treatment regimen (oral agents and/or insulin therapy). Patients with suboptimal control should have intensification of therapy, either by addition or increase in oral agents, addition of basal insulin, or a more complex insulin regimen as warranted by their admission glucose control. Our preliminary experience indicates that measurement of HbA1c on admission is useful in guding treatment regimen at the time of hospital discharge in patients with type 2 diabetes. Patients admitted with a HbA1c <7% can be discharged on the same pre-admission diabetes therapy. Those with HbA1c between 7%-9% can be discharged on oral agents plus basal insulin at 5% of the hospital basal insulin and patients with HbA1c >9% should be discharged on basal bolus insulin or in the combination of metformin plus basal insulin at 8% of hospital dose.

2 This lecture will i) review the results of recent randomized control studies, in non-icu patients with hyperglycemia and diabetes, ii) will present easy to follow insulin- and non-insulin-based treatment regimens for the management of inpatient hyperglycemia; iii) will discuss treatment regimens for the management of patients with diabetes after hospital discharge

3 A Novel Strategy for the Management Inpatient Hyperglycemia in Patients with Type 2 Diabetes Guillermo E. Umpierrez, MD, FACP, FACE Professor of Medicine Director, Clinical Research Diabetes & Metabolism Center Emory University School of Medicine Director, Diabetes & Endocrinology Section Grady Health System Dr. Guillermo Umpierrez, Personal/Professional Financial Relationships with Industry External Industry Relationships Equity, stock, or options in biomedical industry companies or publishers Industry funds to Emory University for my research Industry Advisory/Consultant activities Company Name(s) BMJ Open Diabetes Research & Care Endocrine Society AACE Merck, Sanofi, Novo Nordisk Boehringer Ingelhein Astra Zeneca Sanofi, Merck Role Editor-in-Chief Council At Large Board of Directors Investigator-Initiated Research Projects Advisory Board Objectives Outline current recommendations for the treatment of hyperglycemia in patients hospitalized with type 2 diabetes Discuss the appropriate times to stop and start diabetes meds for patients undergoing surgery Assess the effect of hypoglycemia on clinical outcomes and the importance of avoiding it in hospitalized patients with type 2 diabetes Review the rationale and current data for the use of with insulin and non-insulin agents in hospitalized patients with type 2 diabetes Case Presentation: TJ is a 68 y/o male with an 8 yr history of T2DM admitted with SOB and CHF on chest x-ray. Treated with metformin 1 gram b.i.d. and sitagliptin 1 mg/d. Lab: BG 172 mg/dl, A1c: 8.%; serum creatinine 1.3 mg/dl, egfr: 45 ml/min What is the best treatment option for glycemic control? JP is a 42 y/o male with an 1 yr history of T2DM with diabetic foot infection and osteomyelitis left toe. Treated with metformin 1 g b.i.d. and glipizide 1 mg/d. Lab: BG 294 mg/dl, A1c: 9.2%; serum creatinine 1.4 mg/dl, egfr: 6 ml/min Should both patients be treated with insulin and to the same glucose target? T2DM = type 2 diabetes.; bid = twice daily; egfr = estimated glomerular filtration rate. Diabetes Epidemic in the U.S. US Population 29 million people Inpatient Diabetes 8-9 million hospital discharges Distribution of Patient-Day-Weighted Mean POC-BG Values for ICU ICU Non-ICU Diabetes Prevalence quadrupled, from 5.5 million to 21.9 million between % of all discharges Annual cost: $124 billion (212) 1. CDC s Division of Diabetes Translation ADA. Diabetes Care. 213;36(4): HCUP Nationwide Inpatient Sample (NIS) Data from ~12 million BG readings from 653,359 ICU patients - mean POC-BG: 167 mg/dl POC = point of care. Swanson CM, et al. Endocr Pract. 211;17(6):

4 Composite Complication Rate (%) Hyperglycemia and Pneumonia Outcomes % Admission glucose (mg/dl) BG (mg/dl) < < <25 25 p: <.5 vs BG < 198 mg/dl (11 mmol/l) N= 2,471 patients with CAP McAlister FA, et al. Diabetes Care. 25;28(4):81-5. Mortality Hospital Complications Thirty Day Mortality and In-Hospital Complications in Diabetic and Non-Diabetic Subjects Undergoing Non-Cardiac Surgery % p =.1; p=.1; #p=.17. Frisch A, Umpierrez GE, et al. Diabetes Care. 21;33(8): No diabetes Diabetes Death Pneumonia Skin Sepsis UTI AMI ARF 3,184 non-cardiac surgery patients consecutively admitted to Emory University Hospital between 1/27 and 6/27. # What Glucose Levels Predicts Hospital Complications? ADA, AACE, Endo Composite Complication Rate by Maximum BG Level First 48 hours Maximum BG Umpierrez GE, et al. Endocrine Society Annual Meeting, 214. N= 55,53 patient records in ICU and non- ICU, Emory University Hospitals. Composite of complications: pneumonia, acute renal or respiratory failure, acute MI, bacteremia, and death. Diagnosis & recognition of hyperglycemia and diabetes in the hospital setting No history of diabetes BG<14 mg/dl (7.8 mmol/l) Initiate POC BG monitoring according to clinical status Umpierrez et al. J Clin Endocrinol Metabol. 97(1):16-38, 212 Admission Assess all patients for a history of diabetes Obtain laboratory BG testing on admission No history of diabetes BG >14 mg/dl Start POC BG monitoring x 24-48h Check A1C A1C 6.5% History of diabetes BG monitoring Guideline Recommendations for Glycemic Targets in Non-Critical Care Setting 1. Premeal BG target of <14 mg/dl and random BG <18 mg/dl for the majority of patients American Diabetes Association glucose target mg/dl for most patients with T2DM Recommendations for Managing Patients With Diabetes in Non-ICU Setting Antihyperglycemic Therapy 3. Glycemic targets be modified according to clinical status. - Patients with terminal illness <18-2 mg/dl 4. For avoidance of hypoglycemia, therapy should be reassessed when BG<1 mg/dl Insulin Recommended OADs Not Generally Recommended ADA/AACE Guidelines and Endocrine Society Guidelines: Moghissi ES, et al. Endocrine Pract. 29;15: Umpierrez GE, et al. J Clin Endocrinol Metab. 212;97: American Diabetes Association. Diabetes Care. 216;39(Suppl 1):S99-S14. ACE/ADA Task Force on Inpatient Diabetes: Moghissi ES, et al. Diabetes Care. 29;32(6): Umpierrez GE, et al. J Clin Endocrinol Metab. 212;97:16-38.

5 BG, mg/dl Management of Patients With Diabetes in Non-ICU Settings Discontinue oral antidiabetic agents Insulin naïve: starting total daily dose (TDD):.3 U/kg to.5 U/kg Lower doses in the elderly and renal insufficiency Previous insulin therapy: reduce outpatient insulin dose by 2-25% Basal bolus regimen: Half of TDD as basal and half as rapid-acting insulin before meals SC Insulin Administration Basal Long-acting insulin Scheduled Bolus (Prandial) (SSI only uses this component) Rapid-acting insulin Correction Correction Total daily insulin needs Basal Prandial Umpierrez GE, et al, Diabetes Care. 27;3: Baldwin D, et al. Diabetes Care. 212;35(1): Rubin DJ, et al. Diabetes Care. 211;34: Umpierrez GE, et al. J Clin Endocrinol Metabol. 212;97(1): SSI = sliding scale insulin Moghissi ES, et al; American Association of Clinical Endocrinologists and American Diabetes Association consensus statement on inpatient glycemic control. Endocr Pract. 29;15(4): Umpierrez et al. Endocrine Society Guidelines. J Clin Endocrinol Metabol. 97(1):16-38, 212 with Insulin Analogs vs. Sliding Scale Regular Insulin for the Management of Non-ICU Patients With Type 2 Diabetes Insulin Analogs Inpatient Management in non-icu Sliding Scale Regular Insulin Randomized versus Sliding Scale Regular Insulin in Patients with T2DM (RABBIT-2 Trial) D/C oral antidiabetic drugs on admission Starting total daily dose (TDD):.4 U/kg/d x BG between 14-2 mg/dl.5 U/kg/d x BG between 21-4 mg/dl Half of TDD as basal insulin and half as rapid-acting insulin Insulin glargine - once daily, at the same time/day. Glulisine- three equally divided doses (AC) Umpierrez GE, et al. Diabetes Care. 27;3: Before meal: Supplemental Sliding Scale Insulin (number of units) Add to scheduled insulin dose Bedtime: Blood Give Glucose half of Supplemental Sliding Scale Insulin (mg/dl) Insulin Sensitive Usual Insulin Resistant > > Umpierrez GE, et al. Diabetes Care. 27;3: Sliding Scale Insulin Regimen Rabbit 2 Trial: Changes in Glucose Levels With Basal-Bolus vs. Sliding Scale Insulin a b Basal b b Bolus Group: Sliding-scale BG < 6 mg/dl: 3% BG < 4 Basal-bolus mg/dl: none 12 SSRI: 1 Admit BG 1< 6 mg/dl: 3% Days of Therapy BG < 4 mg/dl: none Sliding scale regular insulin (SSRI) was given 4 times daily Basal-bolus regimen: glargine was given once daily; glulisine was given before meals..4 U/kg/d x BG between 14-2 mg/dl a.5 U/kg/d x BG between 21-4 mg/dl P<.5; b P<.5. Umpierrez GE, et al. Diabetes Care. 27;3(9): a a b Hypoglycemia rate:

6 Glucose media (mg/dl) Outcome Frequency, % Blood Glucose (mg/dl) Insulin Analogs General Surgery RABBIT-2 Surgery Trial: - Research Question: Sliding Scale Regular Insulin T2DM on diet, oral agents or insulin treatment, does treatment with basal bolus regimen with glargine and glulisine is superior to SSRI? Composite of hospital complications: wound infection, pneumonia, respiratory failure, acute kidney injury, and bacteremia Umpierrez GE, et al. Diabetes Care. 211;34(2): Mean BG before meals and at bedtime during basal bolus and SSI therapy 22 Glargine+Glulisine 2 Sliding Scale Insulin Breakfast Lunch Dinner Bedtime p<.1. Umpierrez GE, et al. Diabetes Care. 211;34(2): Postoperative Complications 8.6 P= P=NS P= Glargine+Glulisine Sliding Scale Insulin P= P= Composite Mortality Wound Infection Pneumonia Acute Renal Failure Composite of hospital complications: wound infection, pneumonia, respiratory failure, acute renal failure, and bacteremia. Umpierrez GE, et al. Diabetes Care. 211;34(2): Length of hospital stay, days Hospitalization Outcomes and Costs Patients with complications, n (%) Postsurgical ICU admission, n (%) Total hospitalization costs, USD All (n= 18) (n= 88) SSI (n= 92) p value 7.9 ± ± ± (16%) 6 (7%) 22 (24%).2 23 (13%) 1 (11%) 13 (14%) ± ± ± Inpatient cost per day 4541 ± ± ± 42 Treatment with BB compared with SSI reduced average total inpatient costs per day by $US751 (14%; 95% confidence interval 2 4); Data presented as mean ± SD. Wound infections, pneumonia, acute respiratory failure, acute renal failure, bacteremia Phillips VL, et al. Pharmacoeconom Open. 217;1(2): vs. Premixed Insulin for the Management of Non-ICU Patients With Type 2 Diabetes Inpatient Management in non-icu Mean Daily Blood Glucose During Treatment with and Premixed 3/7 Insulin Regimens 5% Basal 5% Prandial Premixed 7/3 insulin Day of Treatment Basal-bolus Bolus Premixed Mezclas Bellido V, Umpierrez GE, et al. Diabetes Care. 215;38(12):

7 Hypoglycemia During Treatment with and Premixed 3/7 Insulin Inpatient Management in non-icu Setting Insulin Regimen NPH and Regular Insulin Basal-bolus insulin represents a safer regimen than premixed human. Despite the simplicity, premixed human insulin regimen is associated with greatly elevated rates of hypoglycemia and should be used with caution in patients with T2DM. Bellido V, Umpierrez GE, et al. Diabetes Care. 215;38(12): DEAN TRIAL: - Research Question: In patients with T2DM on diet, oral agents or insulin treatment, does treatment with basal bolus regimen with detemir once daily and aspart before meals is superior to NPH and Regular split-mixed insulin regimen? Umpierrez GE, et al. J Clin Endocrinol Metab. 29;94: with Insulin Analogs (glar+glu) vs. Human (NPH+reg) Insulin TODOSALL ANALOGOS ANALOGS HUMANAS NPH+REG Bueno E, et al. Endocr Pract. 215;21(7): TODOS ALL ANALOGOS ANALOGS HUMANAS NPH+REG Prevalence of Hypoglycemia in Patients Treated with Human and Analogs ALL N=134 Analogs N=66 Human n=68 p-value Mild Hypoglycemia p=.68 Severe hypoglucemia Patients withn 2 episodes, n (%) Bueno E, et al. Endocr Pract. 215;21(7): p= p=.2 Management of Patients With Diabetes in the Non-ICU Setting Insulin Recommended Limitations: What is the best insulin Hypoglycemia regimen? Risk Regimen - Multiple injections - Over-treatment in many patients 1. preferred over SSI 2. is preferred over premixed insulin formulations 3.Similar glycemic control but less severe hypoglycemia compared to NPH/Reg insulin Alternatives to Insulin Regimen in Non-ICU Settings Basal Plus (basal + correction) DPP4-inhibitors

8 Insulin Treatment in in Non-ICU Setting T2DM with BG > 14 mg/dl (7.7 mmol/l) NPO Uncertain oral intake Basal insulin - Start at U/Kg/day - Correction doses with rapid acting insulin AC - Adjust basal as needed Adequate Oral intake TDD:.4-.5 U/Kg/day -½ basal, ½ bolus -- adjust as needed Basal Plus Trial Basal + Correction vs. Basal plus Correction Start glargine:.25 U/kg once daily Correction for BG >14 mg/dl per sliding scale Reduce TDD to.15 U/kg in patients 7 yrs and/or serum creatinine 2. mg/dl Regimen Start TDD:.5 U/kg Glargine:.25 U/kg Glulisine:.25 U/kg (AC) Correction for BG >14 mg/dl per sliding scale Reduce TDD to.3 U/kg in patients 7 yrs and/or serum creatinine 2. mg/dl Patients treated with diet, oral agents or with low-dose insulin.4 U/Kg/Day Umpierrez GE, et al. J Clin Endocrinol Metabol. 212;97(1): American Diabetes Association. Standard of Medical Care in Diabetes. Diabetes Care. 217;4 (Supplement 1):S1-S135. Umpierrez GE, et al. Diabetes Care. 213;36(8): Basal-PLUS vs : Medicine and Surgery Patients Medicine Surgery Daily BG Daily BG Insulin Treatment in in Non-ICU Setting T2DM with BG > 14 mg/dl (7.7 mmol/l) NPO Uncertain oral intake Adequate Oral intake BG AC & HS BG AC & HS Basal insulin - Start at U/Kg/day - Correction doses with rapid acting insulin AC - Adjust basal as needed TDD:.4-.5 U/Kg/day -½ basal, ½ bolus - Adjust basal as needed Smiley D, et al. J Diabetes Complications. 213;27(6): American Diabetes Association. Diabetes Care. 217;4 (Supplement 1):S1-S135. Management of Patients With Diabetes with Oral Agents in Non-ICU Settings Regimens 5% Basal 5% Prandial Inpatient Management in non-icu Oral Agents: DPP4-Inhibitors DPP-4 Therapy in Hospitalized Patients Study Type: Multicenter, prospective, open-label randomized clinical trial Patient Population: Patients with T2DM admitted to general medicine and surgery services at 3 hospitals: Emory University, Grady, and University of Michigan Treatment Groups Group 1. Sitagliptin once daily (n=3) Group 2. Sitagliptin plus glargine insulin once daily (n=3) Group 3. Basal bolus regimen with glargine once daily and lispro before meals (n=3) All groups received supplemental doses of lispro for BG > 14 mg/dlbefore meals Umpierrez GE, et al. Diabetes Care. 213;36(11):343-5.

9 BG Concentration (mmol/l) Mean Daily Blood Glucose (mg/dl) Mean Daily BG During Treatment Randomization BG (<18 mg/dl and >18 mg/dl) and Mean Daily Glucose concentration Sitagliptin + Glargine Sitagliptin p=.91 Sita + Basal vs. p= Randomization 12 BG < 18 mg/dl BG > 18 mg/dl Umpierrez GE, et al. Diabetes Care. 213;36(11): Umpierrez GE, et al. Diabetes Care. 213;36(11): Sitagliptin Hospital Trial Research Design and Methods Study Type: Multicenter, prospective, open-label randomized clinical trial Patient Population: Patients with T2DM admitted with BG between 14-4 mg/dl, treated with diet, OADs and insulin at TDD <.6 Unit/kg Treatment Groups Group 1. Sitagliptin plus glargine once daily (n=14) Group 2. Basal bolus regimen with glargine once daily and rapidacting insulin before meals (n=14) Both groups received supplemental (correction) doses of rapid-actin insulin for BG > 14 mg/dl before meals Pasquel FJ, et al. Lancet Diabetes Endocrinol. 217;5(2): Sita-Hospital Trial: Mean Daily BG During Treatment Pasquel FJ, et al. Lancet Diabetes Endocrinol. 217;5(2): Duration of Treatment (days) Sitagliptin + Basal P-value Total daily dose, U/kg/day.2 ±.1.3 ±.2 <.1 Total daily dose, U/day 24.1 ± ± 2.1 <.1 Basal- Glargine, U/day 17.9 ± ± Prandial- aspart/lispro, U/day 11.7 ± 7.9 <.1 Supplements- U/day 5.8 ± ± Number of Injections # injections/day (Hospital stay) # injections/ day (Day 2-1) Insulin Dose and # Injections/day Pasquel FJ, Umpierrez GE, et al. Lancet Diabetes Endocrinol. 217;5(2): ± ±.9 < ± ± 1.1 <.1 Linagliptin Surgery Trial A Randomized Controlled Trial on the Safety and Efficacy of Linagliptin Therapy for the Inpatient Management of General Surgery Patients with Type 2 Diabetes General Surgery Patients Linagliptin General surgery (non-cardiac) patients with T2DM admitted with BG between 14-4 mg/dl, treated with diet, OADs and insulin at TDD <.5 Unit/kg Vellanki & Umpierrez et al. ADA 217 Scientific Meeting.

10 Insulin per day Bloog Glucose (Mg/dL) Insulin per day Bloog Gl Linagliptin Surgery Trial A Randomized Controlled Trial on the Safety and Efficacy of Linagliptin Therapy for the Inpatient Management of General Surgery Patients with Type 2 Diabetes Linagliptin: Linagliptin : 5 mg/day Regimen: Total daily insulin dose:.4 unit/kg/day for BG between 14-2 mg/dl and.5 unit/kg/day for BG between 21-4 mg/dl Half of total daily dose (TDD) given as glargine once daily Half of TDD given as lispro in three equal doses before meals Linagliptin Surgery Trial: Daily Glucose Levels Mean ± SE Supplemental (correction) doses of rapid-acting insulin analog per sliding scale given as needed before meals for BG > 14 mg/dlor bedtime > 2 mg/dl Vellanki & Umpierrez et al. ADA 217 Scientific Meeting. Vellanki & Umpierrez et al. ADA 217 Scientific Meeting. 1 Lina Surgery Trial: Daily Glucose Levels Saxagliptin Saxagliptin in Non-Critically in Non-Critically ill Hospitalized Ill Hospitalized Patients 8 with T2DM and Mild Hyperglycemia D1 D2 D3 D4 D5 D6 Patients with T2D and Mild Hyperglycemia Linagliptin Mean Blood Glucose During Study 3 63% Saxa Group Insulin Group Insulin Use During Study 1 5 Mean ± SE Vellanki & Umpierrez et al. ADA 217 Scientific Meeting. 8 D1 D2 D3 D4 D5 D6 D1 D2 D3 D4 D5 D6 Insulin Use During Study Garg et al. ADA Scientific Meeting, 216 Garg 3 R, et al. BMJ Open Diabetes Res Care. 217;5(1):e D1 D2 D3 D4 D5 D6 Garg et al. ADA Scientific Meeting, 216 Management of General Medicine Patients With T2DM Glucose <2 mg/dl Basal or DPP4-I Basal + DPP4-I Basal: Basal Insulin (glargine, detemir, degludec) once daily at U/kg PLUS correction per sliding scale DPP4-I: Sitagliptin or linagliptin PLUS correction per sliding scale Nauck MA, Meier JJ. Lancet Diabetes Endocrinol. 217;5(2): Glucose >2 mg/dl Basal or Management of Patients With Diabetes After Hospital Discharge or Basal Plus Regimens Inpatient Management in non-icu What Regimen Should We Use at Hospital Discharge?

11 Recommendations for Managing Patients With Diabetes After Hospital Discharge Use admission A1C to adjust therapy at discharge ADD basal or REPLACE with basal/bolus ADD basal insulin therapy Adjust original therapy, ADD another agent or basal insulin Return to original therapy Umpierrez GE, et al. J Clin Endocrinol Metabol. 212;97(1): % 9% 8% 7% A1C < 7% Re-start outpatient treatment regimen (OAD and/or insulin) Umpierrez GE, et al. Diabetes Care. 214;37(11): Discharge Insulin Algorithm Discharge Treatment A1C 7%-9% Re-start outpatient oral agents and D/C on glargine once daily at 5% of hospital dose A1C >9% D/C on basal bolus at same hospital dose. Alternative: re-start oral agents and D/C on glargine once daily at 8% of hospital dose Hospital Discharge Algorithm Based on Admission HbA1C for the Management of Patients with T2DM % % HbA1c 7.9% 7.35% Admission 4 weeks 12 weeks Hospital Discharge Algorithm Based on Admission HbA1C for the Management of Patients with T2DM Primary outcome: - change in A1C at 4 wks and 12 wks after discharge All Patients OAD OAD + Glargine Glargine+ Glulisine Glargine # patients, n (%) (36) 61 (27) 54 (24) 2 (9) A1C Admission, % 8.7± ± ± ± ±2.2 A1C 4 Wks F/U, % 7.9±1.7 7.±1.4 8.±1.4ψ 8.8±1.8ψ 7.7±1.7 A1C 12 Wks F/U, % 7.3± ± ±1.6 8.± ±.8 Hypoglycemia BG<7 mg/dl, n (%) 62 (29) 17 (22) 17 (3) 23 (44) 5 (25) BG<4 mg/dl, n (%) 7 (3) 3 (4) () 3 (6) () Umpierrez GE, et al. Diabetes Care. 214;37(11): Umpierrez GE, et al. ADA Scientific Sessions, 212. p<.1 vs. Admission A1C; ψp=.8 Revised Discharge Insulin Algorithm Discharge Treatment Sitagliptin-Discharge Trial Discharge Treatment A1C < 7% A1C 7%-9% A1C >9% A1C <8% A1C 8%-1% A1C >1% Re-start outpatient treatment regimen (OAD and/or insulin) Umpierrez GE, et al. Diabetes Care. 214;37(11): Re-start outpatient oral agents and D/C on glargine once daily at 5% of hospital dose D/C on basal bolus at same hospital dose. Alternative: re-start oral agents and D/C on glargine once daily at 8% of hospital dose A1C < 7% Sitagliptin ± metformin and/or previous antidiabetic regimen OAD or insulin) Gianchandani R, et al. ADA 216. A1C 7%-9% Sitagliptin ± metformin plus glargine once daily at 5% of hospital dose A1C >9% Sitagliptin ± metformin plus glargine once daily at 8% of hospital dose

12 Sitagliptin-Discharge Trial Changes in HbA1c at 3, 6 Months of Therapy Admission 8.7% Management of diabetes in non-critical care setting 9 % months 7.31% 6 months 7.32% So What really have we learned? Gianchandani R, et al. ADA 216. HbA1c, Duration HbA1c of Follow-Up Case Presentation: TJ is a 68 y/o male with an 8 yr history of DM admitted with SOB and CHF on chest x-ray. Previously treated with metformin 1 gram b.i.d. and sitagliptin 1 mg/day. Lab: BG 172 mg/dl, A1c: 8.%; serum creatinine 1.3 mg/dl, egfr: 45 ml/min JP is a 42 y/o male with an 1 yr history of DM with diabetic foot infection and osteomyelitis left toe. Treated with metformin 1 g b.i.d. and glipizide XL 1 mg/day. Lab: BG 294 mg/dl, A1c: 9.2%; serum creatinine 1.4 mg/dl, egfr: 6 ml/min RABBIT 2 Trial: Changes in Glucose Levels with Basal- Bolus vs Sliding Scale Insulin Individualization of care is needed for the management of hyperglycemia and diabetes in the hospital a P<.5; b P<.5. Sliding scale regular insulin (SSRI) was given 4 times daily; Basal-bolus regimen: glargine was given once daily; glulisine was given before meals;.4 U/kg/day x BG between 14-2 mg/dl;.5 U/kg/d x BG between 21-4 mg/dl. Umpierrez GE, et al. Diabetes Care. 27;3(9): Postoperative Complications Basal-PLUS vs : 3 Medical & Surgical Non-ICU Patients Basal Plus: Glargine once daily.25 U/kg plus glulisine supplements : TTD:.5 U/kg/d Glargine 5% Glulisine 5% Composite of hospital complications: wound infection, pneumonia, respiratory failure, acute renal failure, and bacteremia. Umpierrez GE, et al. Diabetes Care. 211;34(2):1-6. Preliminary results: 51 patients, basal-plus: 49 patients. Umpierrez GE, et al. ADA Scientific Sessions, 212.

13 Blood Glucose (mg/dl) Revised Revised Discharge Insulin Algorithm Re-start outpatient treatment regimen (OAD and/or insulin) Umpierrez GE, et al. Diabetes Care. 214;37(11): Discharge Treatment A1C < 7% A1C 7%-9% A1C >9% A1C <8% A1C 8%-1% A1C >1% Re-start outpatient oral agents and D/C on glargine once daily at 5% of hospital dose Umpierrez et al, Diabetes Care. 214 Nov;37(11): D/C on basal bolus at same hospital dose. Alternative: re-start oral agents and D/C on glargine once daily at 8% of hospital dose DPP4-Inhibitors for the Inpatient Management of General Medicine Medicine and Surgery and Patients Surgery with T2DPatients with T2DM PP4-inhibitors for the Inpatient Management of General DPP4 DPP4 + Glargine Duration of Treatment (days) ed-surg patients, BG between 14 and 4 mg/d treated with diet, OADs or total insulin Umpierrez R, et al. ADA Scientific Meeting unit/kg/day received DPP4-I alone (n=164), DPP4-I plus basal (n=167) or basal bolus 64 med-surg patients, BG14-4 mg/dl treated with diet, OADs or total insulin dose.5 U/kg/day received DPP4-I alone (n=164), DPP4-I plus basal (n=167) or basal bolus (n=39). All groups received correction doses with rapidacting insulin for BG>14 mg/dl. Thank you! geumpie@emory.edu