Transcript - Rockpointe

B1 CASE OPTION SLIDES
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Educational Objectives
At the conclusion of this activity, participants should be able
to demonstrate the ability to:
• Individualize therapies for T2DM during hospital stay and upon release,
accounting for patient presentation, comorbidities, and cause for admission
to reduce risk of readmission due to diabetes-related complications
• Implement strategies to improve glycemic control, including in patients
receiving insulin, while minimizing hypoglycemia risk
• Engage clinical pharmacists to ensure care coordination and educate
patients and caretakers about diabetes management
• Appreciate the impact of national quality initiative requirements for the
management of T2DM patients and analyze in- and out-patient management
modalities that may impact overall quality of care
Polling Question 1
Activity Survey
Please rate your level of confidence in transitioning a patient
with uncontrolled T2DM prior to admission from an in-patient
all-insulin regimen to an effective out-patient
antihyperglycemic regimen:
A. Not confident
B. Slightly confident
C. Confident
D. Very confident
E. Expert
Polling Question 2
Activity Survey
In what percentage of your T2DM patients do you discuss
medication reconciliation and scheduling of follow-up prior to
discharge?
A. All of my T2DM patients
B. 75%-100%
C. 50%-75%
D. <50%
The State of Diabetes Care
and the Place of National
Quality Initiatives
Diagnosed Diabetes
in the US Population (1980-2014)
• Prevalence
quadrupled, from 5.5
million to 21.9 million
21.9 million people
• Incidence tripled
from 493,000 in
1980 to 1.4 million in
2014
CDC’s Division of Diabetes Translation. National Diabetes Surveillance System.
Available at: www.cdc.gov/diabetes/statistics. Accessed: 2/20/2016.
Incidence and Prevalence of In-patient
Diabetes Also Growing
• 23% of all discharges
5518
• 8-9 million discharges
• Annual cost: $124
billion (2012)
2778
• ~20% (1.7-1.9 million)
are early
readmissions with
annual cost: $25
billion
CDC’s Division of Diabetes Translation. Available at: www.cdc.gov/diabetes/statistics/dmany/fig1.htm. Accessed: 2/20/2016.
American Diabetes Association. Diabetes Care. Mar 6 2013.
Healthcare Cost and Utilization Project (HCUP). Agency for Healthcare Research and Quality (AHRQ). 2014.
Available at: http://hcupnet.ahrq.gov/HCUPnet.jsp. Accessed: 3/4/2015.
Prevalence of Diabetes in Hospitals
Is High and Increasing
Number of discharges with
diabetes as first-listed
diagnosis: 635,000
Average length
of stay: 4.6 days
CDC National Center for Health Statistics. Diabetes. Available at: http://www.cdc.gov/nchs/fastats/diabetes.htm.
Accessed: 8/5/2014.
Polling Question 3
Activity Survey
What percentage of patients were readmitted to the hospital
within 30 days?
A. 10%
B. 15%
C. 20%
D. 25%
E. 30%
Hospital Readmissions Reduction Program
• Established by the Affordable Care Act
• Requires CMS to reduce payments to hospitals with excess
readmissions
• Effective October 1, 2012
• Defines readmission as admission for any cause within 30 days of
discharge (i.e. early readmission)
• Applies to certain “index admissions”
– Acute MI, heart failure, and pneumonia
– New as of FY 2015: COPD, total hip arthroplasty (THA), and total knee arthroplasty
(TKA)
Centers for Medicare and Medicaid Services. Readmissions Reduction Program. Available at: www.cms.gov/Medicare/Medicare-Feefor-Service-Payment/AcuteInpatientPPS/Readmissions-Reduction-Program.html. Accessed: 2/20/2016.
Readmissions: Common and Costly
• Costly
–
–
–
–
$556 billion in Medicare spending in 2012
25% of spending are in-patient costs
In-patient costs projected to increase 4%/year
Early readmissions account for $17 billion/year
• Considered a failure of care
– Inadequate relay of information
to post-hospital providers and
patients
– Poor patient compliance
– Inadequate follow-up care
• Common
– 20% of Medicare patients readmitted within
30 days
– Insufficient reliance on family caregivers
– Deterioration of a patient’s clinical condition
– Medical errors
New York Times article. Available at: www.nytimes.com/2012/11/27/health/hospitals-face-pressure-from-medicareto-avert-readmissions.html. Accessed: 2/20/2016.
Jencks SF et al. N Engl J Med. 2009;360:1418-1428.
Vashi AA et al. JAMA. 2013;309:364-371.
Stone J, Hoffman G. Medicare Hospital Readmissions: Issues, Policy Options, and PPACA. Vol 7-5700, R40972:
Congressional Research Service, Penny Hill Press; 2010.
Readmission of Diabetic Patients
• The Urban Diabetes Study, Philadelphia
– 291,752 discharges of diabetic patients over 8 years
– 10.5% hospitalized ≥5 times = 64% all admissions
– 20% readmitted within 30 days
• Overall early readmission rate: 8.5%-13.5%
Robbins JM, Webb DA. Med Care. 2006;44:292-296.
Robbins JM, Webb DA. Am J Public Health. 2006;96:1260-1264.
Pennsylvania Health Care Cost Containment Council, April 2012.
Friedman B et al. Inquiry. 2008-2009;45:408-421.
Vashi AA et al. JAMA. 2013;309:364-371.
Readmission of Diabetic Patients:
Boston Medical Center (BMC)
• 17,595 adults with diabetes discharged
from BMC between 2004 and 2012
• 3,996 early readmissions
• All-cause early readmission rate: 22.7%
• Used multivariable logistic regression to
develop a parsimonious predictive model
Rubin DJ. Curr Diab Rep. 2015;15:584.
22.7%
all-cause
early readmission rate
Themes Associated with
Early Readmission of Diabetic Patients
Poor
Health
Literacy
Health
System
Failure
Failure of
Expected
Protective
Factors
Readmission
Loss of
Control
Over Illness
Social
Determinants
of Health
Impeding Care
Rubin D et al. J Diabetes Complications. 2014;28:869-873.
Reducing Risk of Early Readmission in
Diabetic Patients
• Hospitals must provide comprehensive discharge planning via care
coordination
• ADA Standards of Care 2015
– Discharge planning should start at hospital admission and clear
instructions should be provided at discharge
•
Medication reconciliation
•
Structured discharge communication
•
Diabetes self-management education
– Treatment decisions should be tailored to individual patient preferences
• Individualize therapy
Standards of Medical Care in Diabetes–2015. Diabetes Care. 2015;38(sup 1). Available at: http://care.diabetesjournals.org/
content/suppl/2014/12/23/38.Supplement_1.DC1/January_Supplement_Combined_Final.6-99.pdf.
Challenges in Transition:
A Case-based Approach
T2DM Patient Presenting with
Increasing Frequency of
Shortness-of-Breath Episodes
During the Past Week
Case Study 1
CP, 73-year-old Female
Chief complaint: increasing shortness of breath
• Type 2 diabetes, poorly controlled, treated sitagliptin 100 mg/day and metformin 500 mg twice
daily. Complains of increasing shortness of breath during the past week.
Past medical history
• Type 2 diabetes for 18 years, HbA1c levels between 8.5% and 9.6% during the past 2 years.
Claims good compliance with therapy.
• Hypertension, hypercholesterolemia
• Coronary artery disease
• Prior history of bypass surgery
Patient was sent to the ED for further assessment
of her problem
•
•
•
•
•
•
BP 138/60 mm Hg; HR: 98 bpm; RR: 20 bpm
Weight: 194 lb, BMI: 32 kg/m2
Mild acute distress
Heart: regular, + S3; Lungs: + basal crackles; 1+ edema
Current glucose: 376 mg/dL, HbA1c: 8.8%; creatinine: 1.0 mg/dL
Transferred to the step-down for treatment and observation
Case Study: On Admission
Medications
Metformin 1 g po bid
Sitagliptin 100 mg qd
Laboratory Findings
BG: 376 mg/dL
Creat: 1.0 mL/min
GFR: 52 mL/min/1.73 m2
A1c: 8.8%
Vital Signs
BP: 138/60 mm Hg
HR: 98 bpm;
mild acute distress
Weight: 194 lb
BMI: 32 kg/m2
Case Study
Five days later, heart failure, patient ambulatory with
shortness of breath; Patient is ready for discharge home
Medications During
Hospital Stay
Laboratory Findings
Starting insulin regimen:
Glargine 18 units/d
Insulin lispro 5 units AC
FBG: 156 mg/dL on day of
discharge
Serum Cr: 1.0 mL/min
GFR: 58 mL/min/1.73 m2
A1c: 8.8% (admission)
Insulin at discharge:
Glargine 24 units/d
Insulin lispro 6 units AC
Pre-hospital
Treatment
Metformin 1 g po bid
Sitagliptin 100 mg qd
What’s best treatment at discharge?
Patient Requires Intensification of
Diabetes Regimen
• Long-standing diabetes related to declining beta-cell
function
• OADs maximized; A1c level >8%
• Basal insulin maximized; FBG = 156 mg/dL
• High-dose glucocorticoid usage
OADs = oral antidiabetic drugs
Clinical Inertia on Discharge Planning
Percentage of patient with uncontrolled diabetes discharged with no
change in medications or follow-up HbA1c within 60 d
Griffith ML et al. J Clin Endocrinol Metab. 2006;97:2019-2026.
Polling Question 4
Activity Survey
Which of the following measurements should be used to
adjust antihyperglycemic therapy at discharge for patients
with T2DM?
A. Admission HbA1c level
B. Before breakfast (fasting) glucose level on the day of
discharge
C. Average of before breakfast (fasting) glucose levels during
hospital stay
D. Average of post-meal (2 hour) glucose levels during hospital
stay
Revised Discharge Algorithm
Discharge Treatment
A1c <7%*
A1c 7%-9%*
A1c >9%*
A1c <8%*
A1c 8%-10%*
A1c >10%*
Re-start out-patient
treatment regimen
(OAD and/or insulin)
Re-start out-patient oral
agents and D/C on
glargine once daily at 50%
of hospital dose
*Use admission A1c to adjust therapy at discharge
Umpierrez et al. Diabetes Care. 2014;37:2934-2939.
D/C on basal bolus at same
hospital dose
Alternative: re-start oral
agents and D/C on glargine
once daily at 80%
of hospital dose
Polling Question 5
Activity Survey
The addition of an incretin agent to insulin therapy results in
which of the following?
A. Reduced HbA1c more than insulin alone, but a higher rate
of hypoglycemia
B. Similar HbA1c reduction compared to insulin alone, with a
lower rate of hypoglycemia
C. Reduced HbA1c more than insulin alone, with a lower rate
of hypoglycemia
D. None of the above; insulin alone reduced HbA1c more
than combination therapy, with a reduced rate of
hypoglycemia
Sitagliptin Plus Insulin Glargine in T2DM
• Effect of sitagliptin on insulin dose was assessed in patients
with inadequately controlled T2DM
• 24-week trial, sitagliptin 100 mg/day or placebo was
administered concurrently with insulin glargine titration
• Sitagliptin plus insulin glargine lowered HbA1c more than
placebo plus insulin glargine (between-group difference of
-0.4%; P<0.001) with lower rate of hypoglycemia
• Administering sitagliptin before intensive titration of basal insulin
glargine reduced insulin dose requirement, provided superior
glycemic control with less hypoglycemia compared to an
insulin-only regimen
Mathieu C et al. Diabetes Ther. 2015;6:127-142.
Exenatide BID Added to Basal Insulin
Efficacy and Safety
Adults with T2DM and HbA1c = 7.1% to 10.5% receiving
glargine ± metformin ± pioglitazone were randomized to exenatide
(10 mcg twice a day) or placebo for 30 weeks.
Efficacy
Change in HbA1c (%)
0.0
Glargine + PBO (n=123)
Glargine + EXN (n=138)
-0.5
Outcome
Hypoglycemia†
-1.0
-1.5
*
*
-2.0
Discontinuation due
to adverse events
(% of patients)
†only
-2.5
0
10
20
30
Week
*P<0.001; BID = twice daily; PBO = placebo; EXN = exenatide
Buse JB et al. Ann Intern Med. 2011;154:103-112.
PBO
PEXN
BID value
1.2
1.4
0.49
1
9
<0.01
1 reported event of major hypoglycemia
(PBO group)
GLP-1 RA Added to Basal Insulin vs Basal
Insulin Added to GLP-1 RA
GLP-1 RA Added to
Basal Insulin1
Outcome
Basal Insulin Added to
GLP-1 RA1
EXN BID
PBO
DET + LIRA
LIRA
∆A1c (%)
-1.7a
-1.0
-0.5a
0.0
∆Weight (%)
-1.87a
-0.96
-0.16a
-0.95
25
29
9.2
1.3
Minor
hypoglycemia (%)b
GLP-1RAs and basal insulin combinedc improve glycemic control relative to either
class alone, regardless of order of addition.1-4
Consider lowering basal insulin dose to decrease hypoglycemia risk with GLP-1 Ras.5
aP<0.05; b1
cEXN
major hypoglycemic event occurred in the PBO group of the GLP-1 RA added to basal in study;
BID and LIRA, but not EXN QW, are approved for use with basal, but not prandial insulin.
EXN BID = exenatide twice daily; DET = insulin detemir; LIRA = liraglutide; PBO = placebo; TDD = total daily dose
1. Buse JB et al. Ann Intern Med. 2011;154:103-112.
2. DeVries J et al. Diabetes Care. 2012;35:1446-145.
3. Pawaskar M et al. Endocr Pract. 2012;18:700-711.
4. Li CJ et al. Cardiovasc Diabetol. 2012;11:142.
5. US FDA. Drugs@FDA. Available at: www.accessdata.fda.gov/Scripts/cder/DrugsatFDA.
Case Wrap-up
• Patient was admitted to the hospital because of heart failure
• Prior to hospital admission she was taking metformin and
sitagliptin
– T2DM was poorly controlled; HbA1c at admission was 8.8%
• During the hospital stay, the patient was placed on an all-insulin
regimen
• A change in the patient’s antihyperglycemic regimen is
indicated at the time of discharge because HbA1c >8%
– Insulin glargine plus an incretin-based agent can provide glucose
control while limiting hypoglycemia risk
65-year-old Obese Woman
Presenting with Blood in
the Urine, with a Positive
History of MI
Case Study 2
65-year-old Female
65-year-old woman with obesity and type 2 diabetes for 15
years who presented to the ED with lower abdominal pain,
frequent/painful urination, and blood in the urine
• History of frequent UTIs
• History of MI 5 years ago; family history of heart failure
• Takes metformin 1,000 mg daily and glargine 34 units at night
• Patient states she recently switched to once-daily insulin
because she does not like needles; she has her daughter do
her insulin injections
Case Study 2: Physical Exam and Findings
Physical examination
•
Abdominal obesity (BMI: 42.0 kg/m2)
•
Suprapubic pain
Laboratory evaluation
•
HbA1c: 8.2%
•
eGFR: 92
•
Urinalysis shows hematuria
•
Urine culture shows E coli
•
Random glucose 285 mg/dL and insulin therapy ordered
Polling Question 6
Activity Survey
The patient is admitted to the hospital. How should her
T2DM be managed in the hospital?
A. Keep patient on her current at-home oral
agent/insulin regimen
B. Switch patient to a comparable all-oral
antihyperglycemic agent regimen
C. Switch patient to a comparable all-insulin regimen
D. Stop all antihyperglycemic agents while patient is in
the hospital, but monitor glucose level
Should Oral Hypoglycemic Drugs Be
Discontinued During Hospitalization?
• Insulin is cornerstone of in-patient glycemic management
• Usually oral medications are discontinued
upon hospitalization because:
– Difficult to titrate
– Patients may be NPO
– Contraindications may exist during acute illness
•
e.g. metformin and renal impairment, use of contrast media,
TZDs and heart failure
NPO = nothing by mouth; TZDs = thiazolidinediones
What Comes First Upon Hospital Admission?
• Insulin strategies that are
– Familiar to both providers and nurses in multiple clinical areas
– Consistent with usual hospital practice (e.g. addresses sudden
NPO status, the variability of critical illness, and meal schedule)
– Evidence based
– Flexible enough to allow for optimal safety and individualized
care
– Not tailored to the home environment (because the hospital
is not home)
Polling Question 7
Activity Survey
The patient is ready to be discharged. Her GFR is
unchanged. What is the optimal antihyperglycemic regimen
for this patient on discharge?
A. Keep patient on the all-insulin in-hospital regimen
B. Place patient on the regimen she was on prior to
hospitalization – metformin 1,000 mg daily and
glargine 34 units at night
C. Place the patient on metformin plus a TZD
D. Place the patient on metformin and basal insulin plus
a GLP-1 RA or DPP-4 inhibitor
ADA/EASD General Recommendations for Hyperglycemia Management
Healthy eating, weight control, increased physical activity & diabetes education
Monotherapy
Metformin
Efficacy*
Hypo risk
Weight
Side effects
Costs
high
low risk
neutral/loss
GI / lactic acidosis
low
If HbA1c target not achieved after ~3 months of monotherapy, proceed to 2-drug combination (order not meant to denote
any specific preference - choice dependent on a variety of patient- & disease-specific factors):
Metformin
Dual
therapy†
Efficacy*
Hypo risk
Weight
Side effects
Costs
+
Metformin
+
Metformin
Metformin
+
Metformin
+
+
Metformin
+
Sulfonylurea
Thiazolidinedione
DPP-4
inhibitor
SGLT2
inhibitor
GLP-1 receptor
agonist
Insulin (basal)
high
moderate risk
gain
hypoglycemia
low
high
low risk
gain
edema, HF, fxs
low
intermediate
low risk
neutral
rare
high
intermediate
low risk
loss
GU, dehydration
high
high
low risk
loss
GI
high
highest
high risk
gain
hypoglycemia
variable
If HbA1c target not achieved after ~3 months of dual therapy, proceed to 3-drug combination (order not meant to denote
any specific preference - choice dependent on a variety of patient- & disease-specific factors):
Metformin
+
Triple
therapy
Sulfonylurea
+
TZD
Metformin
+
Thiazolidinedione
+
Metformin
Metformin
+
+
DPP-4
Inhibitor
+
SU
SGLT-2
Inhibitor
+
SU
SU
Metformin
+
GLP-1 receptor
agonist
+
Metformin
+
Insulin (basal)
+
TZD
SU
or
DPP-4-i
or
DPP-4-i
or
TZD
or
TZD
or
TZD
or
DPP-4-i
or
SGLT2-i
or
SGLT2-i
or
SGLT2-i
or
DPP-4-i
or
Insulin§
or
SGLT2-i
or
Insulin§
or
Insulin§
or GLP-1-RA
or GLP-1-RA
or
or
Insulin§
or GLP-1-RA
Insulin§
If HbA1c target not achieved after ~3 months of triple therapy and patient (1) on oral combination, move to injectables, (2) on GLP-1 RA, add
basal insulin, or (3) on optimally titrated basal insulin, add GLP-1-RA or mealtime insulin. In refractory patients consider adding TZD or SGL T2-i:
Metformin
Combination
injectable
therapy‡
+
Basal Insulin +
Inzucchi SE et al. Diabetes Care. 2015;38:140-149.
Mealtime Insulin or
GLP-1-RA
GLP = glucagon-like peptide; DPP4 = Dipeptidyl peptidase-4
Expected HbA1c Reduction of
Antihyperglycemic Agents
Drug Class
Expected HbA1c Reduction
Biguanide
1%-2%
SU (2nd Generation)
1%-2%
TZD
GLP-1 RA
1%-1.5%
0.5%-1.5%
DPP-4 inhibitor
0.5%-1%
SGLT-2 inhibitor
0.5%-1%
Mayo Foundation for Medical Education and Research. Diabetes medication choice, 2014.
Available at: http://shareddecisions.mayoclinic.org.
Allen J, Freitas S. Comparison chart of glucose-lowering agents for management of type 2 diabetes mellitus. October 2015.
Consideration for
Selection
Glitazones and CV Mortality
Rosiglitazone
Pioglitazone
• Meta-analysis1 of small trials,
DREAM and ADOPT
• Meta-analysis3 of 19 trials
– MI risk increased 43% (P=0.03)
– CV death risk increased 64% (P=0.06)
– Risk of CV death was double the
comparator (P=0.02)
• MI risk confirmed with longer-term
meta-analysis2
• The primary outcome (death, nonfatal MI, non-fatal stroke) was 18%
LESS common with pioglitazone
(P=0.005)
– Pioglitazone: 4.4%
– Control: 5.7%
All prescribing restrictions imposed by the FDA have been lifted, except for CHF risk,
which is substantially increased with both rosiglitazone and pioglitazone
(relative increase 50%-100%, absolute increase 1%-2%)4,5
1. Nissen SE et al. N Engl J Med. 2007;356:2457-2471.
2. Singh S et al. JAMA. 2007; 298:1189-1195.
3. Lincoff AM et al. JAMA. 2007;298:1180-1188.
4. Nissen SE et al. N Engl J Med. 2007;356:2457-2471.
5. Singh S et al. JAMA. 2007;298:1189-1195.
Cardiovascular Considerations for
DPP-4 Inhibitors
Trial description
Risk of major CV events
HF
Alogliptin (EXAMINE: n = 5390;
median follow-up, 18 months)1
No increased riska
Equivocal risk
Saxagliptin (SAVOR: n = 16,492;
median follow-up, 2.1 years)2
No increased riska
More hospitalizations
(P = 0.007)
Sitagliptin (TECOS: n = 14,724;
median follow-up, ≈ 3 years)3
No increased riska
No increased risk
• Recent meta-analysis affirms no increased risk of mortality, MI, or stroke with DPP-4 inhibitors4,b
• US FDA advisory committee – new labeling information regarding potential HF risk with alogliptin
and saxagliptin, but CV safety profile is acceptable5
• Long-term CV safety trials are in progress for linagliptin6
a
Primary endpoint: composite of death
from CV causes, nonfatal MI, nonfatal
stroke, unstable angina (sitagliptin)
1. White WB et al. N Engl J Med. 2013;369:1327-1335.
b 94 RCTs for alogliptin, linagliptin,
2. Scirica BM et al. N Engl J Med. 2013;369:1317-1326.
saxagliptin, sitagliptin, vildagliptin vs PBO
3. Results from TECOS. Presented at the ADA 75th Scientific Sessions. Available at:
or active control (n=85,244; 29 weeks of
professional.diabetes.org/presentations_details.aspx?session=4723.
median follow-up)
4. Savarese G et al. Int J Cardiol. 2014;181C:239-244.
5. MedPage Today. Available at: www.medpagetoday.com/Cardiology/Diabetes/51003.
6. ClinicalTrials.gov. Available at: clinicaltrials.gov/ct2/results?term=linagliptin+stroke&Search=Search.
Cardiovascular Considerations with GLP-1 RAs
• Recent meta-analysis of CV risk1
– ALBI, EXN BID, EXN QW, LIRA, and TASPO trials
– Short-terma trials of individuals with low CV risk
– No increased risk of major adverse cardiovascular event (MACE), acute MI,
stroke, all-cause mortality, or CV death vs comparators
Agent – Trial Titlea
Status of Long-Term CV Safety Trials in Populations at
Increased Risk for CV Events
Lixisenatide – ELIXA2,3
Completed 2/2015b – non-inferior to PBO for CVsafety3,c
Liraglutide – LEADER4
Preliminary results released 3/2016 – non-inferiority to PBO, plus
statistically significant reduction
Exenatide QW – EXSCEL2
Anticipated completion 4/20182
Dulaglutide – REWIND2
Anticipated completion 4/20192
1. Monami M et al. Diabetes Obes Metab. 2014;16:38-47.
2. ClinicalTrials.gov. Available at: www.clinicaltrials.gov.
3. Sanofi press release. Available at: www.news.sanofi.us/2015-03-19-Sanofi-AnnouncesTop-Line-Results-for-Cardiovascular-Outcomes-Study-of-Lyxumia-lixisenatide.
4. Novo Nordisk press release. Available at: http://www.ft.com/fastft/2016/03/04/novo-nordiskdiabetes-drug-cuts-heart-risk-trial-shows/.
Most trials 24-52 weeks
Complete results to be presented at
2015 ADA Scientific Sessions
c Time to first MACE
a
b
Other Considerations with Incretin Agents
• Side effect with GLP-1 RA: nausea/vomiting
• No added hypoglycemia unless used with secretagogue or insulin
• C-cell hyperplasia and medullary cancer in rodents
• Pancreatitis:
– FDA investigated potential pancreatic toxicity associated with incretins and concluded that
available data do not confirm causal relationship between GLP-1 therapies and increased
risk for pancreatic side effects.
– Meta-analysis of 2 case-control and 6 retrospective cohort studies (1,324,515 patients)
showed odds ratio for acute pancreatitis = 1.03 (95% CI 0.87 -1.20) in patients receiving
exenatide, liraglutide, sitagliptin, saxagliptin, vildagliptin, or linagliptin. Authors’ conclusion:
no suggestion that acute pancreatitis is associated with incretin agents.
– More recent data showed sitagliptin was not associated with an increased risk of acute
pancreatitis in high-risk diabetic patients with hypertriglyceridemia or those with history of
acute pancreatitis.
FDA. FDA Drug Safety Communication. 3-14-2013. Available at: www.fda.gov/drugs/drugsafety/ucm343187.htm.
Brooks M. FDA sides with EMA on incretin diabetes drugs. 8-1-2013. Available at: www.medscape.com/viewarticle/808830.
Wang T et al. Diabetes Obes Metab. 2015;17:32-41.
Chang CH et al. Medicine (Baltimore). 2016;95:e2603.
Cardiovascular Safety of SGLT-2 Inhibitors
• EMPA-REG-OUTCOME1
– n = 7,034 T2DM patients
– Primary endpoint = time to first occurrence of either CV death or
non-fatal myocardial infarction or non-fatal stroke
– Empagliflozin was superior to standard of care in CV risk reduction
Agent – Trial Title
Status of Long-term CV Safety Trials in Populations at
Increased Risk for CV Events
Empagliflozin – EMPA-REG
Superior to standard of care for CV risk reduction
Dapagliflozin – DECLARE
Anticipated completion 2019
Canagliflozin – CANVAS
Anticipated completion 2017
1. Available at: www.boehringer-ingelheim.com/news/news_releases/press_releases/2015/20_august_2015_diabetes.html.
Other Considerations with SGLT-2 Inhibitors
• Genital infections
– Patients are either treated with antifungal or antibiotic agents or self treated.
• Fracture
– Use of dapagliflozin in moderate renal impairment leads to increased fractures.
• Bladder cancer?
– Dapagliflozin groups had higher than expected risk of bladder cancer. However, it is possible that
genitourinary side effects lead to increased cancer detection.
– Canagliflozin shows no increase in cancer.
• Serious urinary tract infections
– The FDA issued a warning due to reported cases of urosepsis.
• Ketoacidosis
– Postmarketing cases have been reported to the FDA; insulin-deficient patients appear to be
most at risk.
– The FDA updated the warning in Dec 2015 to recommend stopping the drug and immediately
seeking treatment for symptoms of ketoacidosis.
Case Study 2: Considerations for Discharge
• Frequent urinary tract infections
– Patient given course of ciprofloxacin to keep at home for repeat infection
– Instructed to drink more water daily and use proper hygiene measures
• Duration of diabetes and insulin insufficiency
– Control is suboptimal on admission regimen of metformin and basal insulin
alone
– Because of reluctance with using needles, the patient was referred to a
pharmacist diabetes educator for teaching and to address other barriers to
adherence
• Obesity
– Strategies that minimize weight gain or facilitate weight loss would be ideal
What is the optimal treatment choice for this patient?
Profiles of Antidiabetic Medications
Of the recommended options for this
patient, the DPP-4i class is
associated with the fewest cautions.
HbA1c lowering 0.5% – 0.9%
Copyright © 2013 AACE. May not be reproduced in any form without express written permission from AACE.
“Survival Skills” to Be Taught Before Discharge
How and when to take medication/insulin
What to expect from the medication
How/when to test BG (SMBG)
What are target glucose levels
Basics on meal planning
How to treat hypoglycemia
Sick-day management plan
Date/time of follow-up visits
Including diabetes education
When and who to call on the health care team
What community resources are available
Moghissi ES et al. Endocr Pract. 2009;15:353-369.
Transition from Hospital to Out-patient Care
• Preparation for transition to the out-patient setting should
begin at the time of hospital admission
• Clear communication with out-patient providers is critical
for ensuring safe and successful transition to out-patient
management
• Collaboration between the patient and/or significant other
with entire interdisciplinary team is crucial in successful
discharge planning
Umpierrez GE et al. J Clin Endocrinol Metab. 2012;97:16-38.
Available at: www.ntocc.org. Accessed: August 5, 2014.
Polling Question 8
Activity Survey
Your pharmacist can help in transitioning your patient from
hospital to home and reduce readmission by:
A. Prescribing an injectable agent to patients with HbA1c >8%
B. Determining factors that caused admission or readmission
and counsel about medication
C. Discussing medication discontinuation strategies with the
patients when side effects occur
D. All of the above
Multidisciplinary Approach to Managing
In-patient Hyperglycemia across Patient
Transitions
Hospitalist/
Endocrinologist
Nurse
Primary Care Physician
Patients/
Their family
Pharmacist
Hospital
Care Coordinator
Diabetes Educator/Dietitian
Hospital Discharge Transition
From Hospital to Home
• Stabilize blood glucose prior to discharge
• Obtain A1c for discharge planning if result not available
for the previous 2 to 3 months
• Provide in-patient education (survival skills)
• Refer patient for out-patient education
– ADA-recognized education programs (www.diabetes.org)
• Prepare for out-patient follow-up with PCP
– Inform PCP and health care team of new medications and rationales for change
– Utilize the clinical pharmacist for discharge-medication counseling and care coordination
around ensuring prescription access
Magee MF. Hosp Physician. 2006;2:17-28.
Clement S et al. Diabetes Care. 2004;27:553-591.
Inzucchi SE. N Engl J Med. 2006;355:1903-1911.
Hassan E. Am J Health Syst Pharm. 2007;64(10 suppl 6):S9-S14.
Medication Management in Care Transitions
• Pharmacist is uniquely
positioned and qualified to
provide medication
management in care
transitions (MMCT)
• Support medication
adherence by providing
patient-centered medication
management
• Reduce risk of medication
related problems (MRPs)
through care coordination
(discharge planning)
ASHP Intersections. Available at: www.ashpintersections.org/2013/09/hens-offeropportunities-for-pharmacists-to-improve-patient-care. Accessed: 2/20/2016.
Medication Management in Care Transitions
Phase of Care
Admission
During
Hospitalization
Discharge
Home
Role of the Pharmacist
Medication Assessment
at Admission
Determine factors in
admission/readmission
• Medication history
• Medication reconciliation
• Adverse drug events (ADE)
• Medication adherence
• Medication access
Anticipate post-discharge
needs
• Caregiver support
• Barriers to adherence
Optimizing Therapy
Discharge Planning
Provide patient counseling
• Identify barriers to learning
• Medication management
• Disease self-management
• Medication adherence
• Use “Teach Back” method
• Provide tools
Review medication regimen
• Medication reconciliation
• Provide medication list and
related information to:
- Patient/caregiver
- Physician/medical team
- Pharmacy/pharmacist
- Home health nurse
Optimize the medication
regimen
• Initiate indicated medications
(EBM)
• Discontinue unnecessary or
unsafe medications
• Simplify the medication
regimen
Verify appropriate postdischarge care plan
• Ensure plan for medication
access
• Ensure appropriate discharge
follow-up according to need
• Ensure proper information is
provided regarding contact
information, action plan for
care, and symptom or AE
management
Adapted from Washington Patient Safety Coalition. Available at: www.wapatientsafety.org.
Post-Discharge
Medication Management
Contact patient/caregiver
• In person or virtual
encounter
Review patient status and
medication
• Medication reconciliation
• Medication adherence
• ADE monitoring
• Medication access
• Medication management/
disease management
Communicate to other
providers any pertinent
medical information or
findings
Medication Management in Care Transitions
• Medication management is a major component of
advanced discharge planning and transitional care
– More post-discharge adverse events are related to drugs
than other causes
– Lack of adherence to medication prescribed at discharge
has been shown to be a driver of post-discharge adverse
drug events
• $100 billion per year = estimated aggregate cost of hospital
admissions related to medication adherence
Improving Medication Adherence and Reducing Readmissions. The Network for Excellence in Health Innovation
(NEHI). 2012. Available at: www.nacds.org/pdfs/pr/2012/nehi-readmissions.pdf.
Key Take-away Messages
1. Diabetes is a common diagnosis in the hospital setting;
hospitalization provides an opportunity to identify and improve
glycemic control
2. The many transitions of care during hospitalization and back to
the out-patient setting can create challenges to glycemic control
3. A team approach, medication reconciliation, and policies to
manage hyperglycemia and insulin therapy can improve diabetes
care
4. Patients with diagnosed diabetes or newly diagnosed diabetes
may require changes to or intensification of therapy and
appropriate education
CME Credit
•
Post-activity Survey
– Now that the program has completed, please take a
moment to answer the Post-activity Survey questions on
your form
– Your answers are important and will help us identify
remaining educational gaps and shape future CME activities
•
CME Evaluation
– If you’re seeking credit, ensure you’ve filled in your name
and demographic information on page 1 and complete the
CME Evaluation on your form (after the Post-activity Survey)
– Return all forms to on-site CME staff
Thank you for joining us today!
B2 CASE OPTION SLIDES
Begin Here
Please Help Us with the Following
Prior to the start of the program, check your syllabus to
ensure you have the following printed program materials:
•
Participant Survey and CME Evaluation
– In the front of your syllabus
– Remove from your packet
– Fill out the demographic information at the top
– Throughout the program, please take a moment to answer
the corresponding Activity Survey questions on this form
(slides will be marked as “Polling Questions” throughout the
deck)
Disclosures
All relevant financial relationships with commercial interests
reported by faculty speakers, steering committee members,
non-faculty content contributors and/or reviewers, or their
spouses/partners have been listed in your program syllabus.
Off-label Discussion Disclosure
This educational activity may contain discussion of published and/or
investigational uses of agents that are not indicated by the Food and Drug
Administration. PCME does not recommend the use of any agent outside of
the labeled indications. Please refer to the official prescribing information for
each product for discussion of approved indications, contraindications and
warnings. The opinions expressed are those of the presenters and are not to
be construed as those of the publisher or grantors.
Educational Objectives
At the conclusion of this activity, participants should be able
to demonstrate the ability to:
• Individualize therapies for T2DM during hospital stay and upon release,
accounting for patient presentation, comorbidities, and cause for admission
to reduce risk of readmission due to diabetes-related complications
• Implement strategies to improve glycemic control, including in patients
receiving insulin, while minimizing hypoglycemia risk
• Engage clinical pharmacists to ensure care coordination and educate
patients and caretakers about diabetes management
• Appreciate the impact of national quality initiative requirements for the
management of T2DM patients and analyze in- and out-patient management
modalities that may impact overall quality of care
Polling Question 1
Activity Survey
Please rate your level of confidence in transitioning a patient
with uncontrolled T2DM prior to admission from an in-patient
all-insulin regimen to an effective out-patient
antihyperglycemic regimen:
A. Not confident
B. Slightly confident
C. Confident
D. Very confident
E. Expert
Polling Question 2
Activity Survey
In what percentage of your T2DM patients do you discuss
medication reconciliation and scheduling of follow-up prior to
discharge?
A. All of my T2DM patients
B. 75%-100%
C. 50%-75%
D. <50%
The State of Diabetes Care
and the Place of National
Quality Initiatives
Diagnosed Diabetes
in the US Population (1980-2014)
• Prevalence
quadrupled, from 5.5
million to 21.9 million
21.9 million people
• Incidence tripled
from 493,000 in
1980 to 1.4 million in
2014
CDC’s Division of Diabetes Translation. National Diabetes Surveillance System.
Available at: www.cdc.gov/diabetes/statistics. Accessed: 2/20/2016.
Incidence and Prevalence of In-patient
Diabetes Also Growing
• 23% of all discharges
5518
• 8-9 million discharges
• Annual cost: $124
billion (2012)
2778
• ~20% (1.7-1.9 million)
are early
readmissions with
annual cost: $25
billion
CDC’s Division of Diabetes Translation. Available at: www.cdc.gov/diabetes/statistics/dmany/fig1.htm. Accessed: 2/20/2016.
American Diabetes Association. Diabetes Care. Mar 6 2013.
Healthcare Cost and Utilization Project (HCUP). Agency for Healthcare Research and Quality (AHRQ). 2014.
Available at: http://hcupnet.ahrq.gov/HCUPnet.jsp. Accessed: 3/4/2015.
Prevalence of Diabetes in Hospitals
Is High and Increasing
Number of discharges with
diabetes as first-listed
diagnosis: 635,000
Average length
of stay: 4.6 days
CDC National Center for Health Statistics. Diabetes. Available at: http://www.cdc.gov/nchs/fastats/diabetes.htm.
Accessed: 8/5/2014.
Polling Question 3
Activity Survey
What percentage of patients were readmitted to the hospital
within 30 days?
A. 10%
B. 15%
C. 20%
D. 25%
E. 30%
Hospital Readmissions Reduction Program
• Established by the Affordable Care Act
• Requires CMS to reduce payments to hospitals with excess
readmissions
• Effective October 1, 2012
• Defines readmission as admission for any cause within 30 days of
discharge (i.e. early readmission)
• Applies to certain “index admissions”
– Acute MI, heart failure, and pneumonia
– New as of FY 2015: COPD, total hip arthroplasty (THA), and total knee arthroplasty
(TKA)
Centers for Medicare and Medicaid Services. Readmissions Reduction Program. Available at: www.cms.gov/Medicare/Medicare-Feefor-Service-Payment/AcuteInpatientPPS/Readmissions-Reduction-Program.html. Accessed: 2/20/2016.
Readmissions: Common and Costly
• Costly
–
–
–
–
$556 billion in Medicare spending in 2012
25% of spending are in-patient costs
In-patient costs projected to increase 4%/year
Early readmissions account for $17 billion/year
• Considered a failure of care
– Inadequate relay of information
to post-hospital providers and
patients
– Poor patient compliance
– Inadequate follow-up care
• Common
– 20% of Medicare patients readmitted within
30 days
– Insufficient reliance on family caregivers
– Deterioration of a patient’s clinical condition
– Medical errors
New York Times article. Available at: www.nytimes.com/2012/11/27/health/hospitals-face-pressure-from-medicareto-avert-readmissions.html. Accessed: 2/20/2016.
Jencks SF et al. N Engl J Med. 2009;360:1418-1428.
Vashi AA et al. JAMA. 2013;309:364-371.
Stone J, Hoffman G. Medicare Hospital Readmissions: Issues, Policy Options, and PPACA. Vol 7-5700, R40972:
Congressional Research Service, Penny Hill Press; 2010.
Readmission of Diabetic Patients
• The Urban Diabetes Study, Philadelphia
– 291,752 discharges of diabetic patients over 8 years
– 10.5% hospitalized ≥5 times = 64% all admissions
– 20% readmitted within 30 days
• Overall early readmission rate: 8.5%-13.5%
Robbins JM, Webb DA. Med Care. 2006;44:292-296.
Robbins JM, Webb DA. Am J Public Health. 2006;96:1260-1264.
Pennsylvania Health Care Cost Containment Council, April 2012.
Friedman B et al. Inquiry. 2008-2009;45:408-421.
Vashi AA et al. JAMA. 2013;309:364-371.
Readmission of Diabetic Patients:
Boston Medical Center (BMC)
• 17,595 adults with diabetes discharged
from BMC between 2004 and 2012
• 3,996 early readmissions
• All-cause early readmission rate: 22.7%
• Used multivariable logistic regression to
develop a parsimonious predictive model
Rubin DJ. Curr Diab Rep. 2015;15:584.
22.7%
all-cause
early readmission rate
Themes Associated with
Early Readmission of Diabetic Patients
Poor
Health
Literacy
Health
System
Failure
Failure of
Expected
Protective
Factors
Readmission
Loss of
Control
Over Illness
Social
Determinants
of Health
Impeding Care
Rubin D et al. J Diabetes Complications. 2014;28:869-873.
Reducing Risk of Early Readmission in
Diabetic Patients
• Hospitals must provide comprehensive discharge planning via care
coordination
• ADA Standards of Care 2015
– Discharge planning should start at hospital admission and clear
instructions should be provided at discharge
•
Medication reconciliation
•
Structured discharge communication
•
Diabetes self-management education
– Treatment decisions should be tailored to individual patient preferences
• Individualize therapy
Standards of Medical Care in Diabetes–2015. Diabetes Care. 2015;38(sup 1). Available at: http://care.diabetesjournals.org/
content/suppl/2014/12/23/38.Supplement_1.DC1/January_Supplement_Combined_Final.6-99.pdf.
Challenges in Transition:
A Case-based Approach
T2DM Patient Presenting with
Increasing Frequency of
Shortness-of-Breath Episodes
During the Past Week
Case Study 1
CP, 73-year-old Female
Chief complaint: increasing shortness of breath
• Type 2 diabetes, poorly controlled, treated sitagliptin 100 mg/day and metformin 500 mg twice
daily. Complains of increasing shortness of breath during the past week.
Past medical history
• Type 2 diabetes for 18 years, HbA1c levels between 8.5% and 9.6% during the past 2 years.
Claims good compliance with therapy.
• Hypertension, hypercholesterolemia
• Coronary artery disease
• Prior history of bypass surgery
Patient was sent to the ED for further assessment
of her problem
•
•
•
•
•
•
BP 138/60 mm Hg; HR: 98 bpm; RR: 20 bpm
Weight: 194 lb, BMI: 32 kg/m2
Mild acute distress
Heart: regular, + S3; Lungs: + basal crackles; 1+ edema
Current glucose: 376 mg/dL, HbA1c: 8.8%; creatinine: 1.0 mg/dL
Transferred to the step-down for treatment and observation
Case Study: On Admission
Medications
Metformin 1 g po bid
Sitagliptin 100 mg qd
Laboratory Findings
BG: 376 mg/dL
Creat: 1.0 mL/min
GFR: 52 mL/min/1.73 m2
A1c: 8.8%
Vital Signs
BP: 138/60 mm Hg
HR: 98 bpm;
mild acute distress
Weight: 194 lb
BMI: 32 kg/m2
Case Study
Five days later, heart failure, patient ambulatory with
shortness of breath; Patient is ready for discharge home
Medications During
Hospital Stay
Laboratory Findings
Starting insulin regimen:
Glargine 18 units/d
Insulin lispro 5 units AC
FBG: 156 mg/dL on day of
discharge
Serum Cr: 1.0 mL/min
GFR: 58 mL/min/1.73 m2
A1c: 8.8% (admission)
Insulin at discharge:
Glargine 24 units/d
Insulin lispro 6 units AC
Pre-hospital
Treatment
Metformin 1 g po bid
Sitagliptin 100 mg qd
What’s best treatment at discharge?
Patient Requires Intensification of
Diabetes Regimen
• Long-standing diabetes related to declining beta-cell
function
• OADs maximized; A1c level >8%
• Basal insulin maximized; FBG = 156 mg/dL
• High-dose glucocorticoid usage
OADs = oral antidiabetic drugs
Clinical Inertia on Discharge Planning
Percentage of patient with uncontrolled diabetes discharged with no
change in medications or follow-up HbA1c within 60 d
Griffith ML et al. J Clin Endocrinol Metab. 2006;97:2019-2026.
Polling Question 4
Activity Survey
Which of the following measurements should be used to
adjust antihyperglycemic therapy at discharge for patients
with T2DM?
A. Admission HbA1c level
B. Before breakfast (fasting) glucose level on the day of
discharge
C. Average of before breakfast (fasting) glucose levels during
hospital stay
D. Average of post-meal (2 hour) glucose levels during hospital
stay
Revised Discharge Algorithm
Discharge Treatment
A1c <7%*
A1c 7%-9%*
A1c >9%*
A1c <8%*
A1c 8%-10%*
A1c >10%*
Re-start out-patient
treatment regimen
(OAD and/or insulin)
Re-start out-patient oral
agents and D/C on
glargine once daily at 50%
of hospital dose
*Use admission A1c to adjust therapy at discharge
Umpierrez et al. Diabetes Care. 2014;37:2934-2939.
D/C on basal bolus at same
hospital dose
Alternative: re-start oral
agents and D/C on glargine
once daily at 80%
of hospital dose
Polling Question 5
Activity Survey
The addition of an incretin agent to insulin therapy results in
which of the following?
A. Reduced HbA1c more than insulin alone, but a higher rate
of hypoglycemia
B. Similar HbA1c reduction compared to insulin alone, with a
lower rate of hypoglycemia
C. Reduced HbA1c more than insulin alone, with a lower rate
of hypoglycemia
D. None of the above; insulin alone reduced HbA1c more
than combination therapy, with a reduced rate of
hypoglycemia
Sitagliptin Plus Insulin Glargine in T2DM
• Effect of sitagliptin on insulin dose was assessed in patients
with inadequately controlled T2DM
• 24-week trial, sitagliptin 100 mg/day or placebo was
administered concurrently with insulin glargine titration
• Sitagliptin plus insulin glargine lowered HbA1c more than
placebo plus insulin glargine (between-group difference of
-0.4%; P<0.001) with lower rate of hypoglycemia
• Administering sitagliptin before intensive titration of basal insulin
glargine reduced insulin dose requirement, provided superior
glycemic control with less hypoglycemia compared to an
insulin-only regimen
Mathieu C et al. Diabetes Ther. 2015;6:127-142.
Exenatide BID Added to Basal Insulin
Efficacy and Safety
Adults with T2DM and HbA1c = 7.1% to 10.5% receiving
glargine ± metformin ± pioglitazone were randomized to exenatide
(10 mcg twice a day) or placebo for 30 weeks.
Efficacy
Change in HbA1c (%)
0.0
Glargine + PBO (n=123)
Glargine + EXN (n=138)
-0.5
Outcome
Hypoglycemia†
-1.0
-1.5
*
*
-2.0
Discontinuation due
to adverse events
(% of patients)
†only
-2.5
0
10
20
30
Week
*P<0.001; BID = twice daily; PBO = placebo; EXN = exenatide
Buse JB et al. Ann Intern Med. 2011;154:103-112.
PBO
PEXN
BID value
1.2
1.4
0.49
1
9
<0.01
1 reported event of major hypoglycemia
(PBO group)
GLP-1 RA Added to Basal Insulin vs Basal
Insulin Added to GLP-1 RA
GLP-1 RA Added to
Basal Insulin1
Outcome
Basal Insulin Added to
GLP-1 RA1
EXN BID
PBO
DET + LIRA
LIRA
∆A1c (%)
-1.7a
-1.0
-0.5a
0.0
∆Weight (%)
-1.87a
-0.96
-0.16a
-0.95
25
29
9.2
1.3
Minor
hypoglycemia (%)b
GLP-1RAs and basal insulin combinedc improve glycemic control relative to either
class alone, regardless of order of addition.1-4
Consider lowering basal insulin dose to decrease hypoglycemia risk with GLP-1 Ras.5
aP<0.05; b1
cEXN
major hypoglycemic event occurred in the PBO group of the GLP-1 RA added to basal in study;
BID and LIRA, but not EXN QW, are approved for use with basal, but not prandial insulin.
EXN BID = exenatide twice daily; DET = insulin detemir; LIRA = liraglutide; PBO = placebo; TDD = total daily dose
1. Buse JB et al. Ann Intern Med. 2011;154:103-112.
2. DeVries J et al. Diabetes Care. 2012;35:1446-145.
3. Pawaskar M et al. Endocr Pract. 2012;18:700-711.
4. Li CJ et al. Cardiovasc Diabetol. 2012;11:142.
5. US FDA. Drugs@FDA. Available at: www.accessdata.fda.gov/Scripts/cder/DrugsatFDA.
Case Wrap-up
• Patient was admitted to the hospital because of heart failure
• Prior to hospital admission she was taking metformin and
sitagliptin
– T2DM was poorly controlled; HbA1c at admission was 8.8%
• During the hospital stay, the patient was placed on an all-insulin
regimen
• A change in the patient’s antihyperglycemic regimen is
indicated at the time of discharge because HbA1c >8%
– Insulin glargine plus an incretin-based agent can provide glucose
control while limiting hypoglycemia risk
72-year-old Woman
Presenting with a
Comminuted Hip Fracture
Case Study 2
72-year-old Female
• Mrs. S is a 72-year-old woman with type 2 diabetes for 20
years, who fell on her kitchen floor while preparing a meal.
She sustained a comminuted hip fracture.
• She reports she was hungry and “shaky” prior to her fall
and does not remember details prior to EMS arriving. Her
glucose was 38 upon POC check by EMS
• She takes glipizide 10 mg twice daily and pioglitazone 45
mg daily; her most recent HbA1c 2 months ago was 7.3%.
Case Study 2: Physical Exam and Findings
• Physical examination
– Frail appearance (BMI: 19.0 kg/m2)
– Kyphosis evident
– Normal cardiovascular examination, no edema
• Laboratory evaluation
– Random glucose on chemistry panel: 68 mg/dL; HbA1c: 6.1%
– SCr: 1.7; eGFR: 28 mL/min/1.73 m2
• CXR: normal
TZD and Bone Fracture
• TZDs associated with 1.3-fold increased risk for osteoporotic
fracture compared with other antidiabetic medications1
• Data show TZDs decreased bone density in hip and lumbar
spine in women2,3
• Meta-analysis of 10 studies showed increased risk for
fracture in upper arm, hand, and foot4
• TZDs decrease BMD by activating peroxisome proliferator –
activated receptors5
1.
2.
3.
4.
5.
Bazelier MT et al. Pharmacoepidemiol Drug Saf. 2012;21:507-514.
Glintborg D et al. J Clin Endocrinol Metab. 2008;93:1696-1701.
Grey A et al. J Clin Endocrinol Metab. 2007;92:1305-1310.
Loke YK et al. CMAJ. 2009;80:32-39.
Syversen U et al. BMC Endocr Disord. 2009;9:10.
Hypoglycemia with Sulfonylureas
• Sulfonylureas increase insulin secretion, increasing the risk of
hypoglycemia by 4%-9% compared to placebo or other agents
• Characteristics that raise concern for increased risk of
hypoglycemia include:
-
Using longer-acting sulfonylureas (e.g. glyburide)
-
Renal insufficiency
-
Frail elderly
UK Prospective Diabetes Study (UKPDS 33). Lancet. 1998;352:837-853.
Polling Question 6
Activity Survey
The patient is admitted to the hospital. How should her
T2DM be managed in the hospital:
A. Keep patient on her current at-home regimen
B. Switch patient to a comparable all-insulin regimen
C. Switch patient to comparable regimen with meal-time
insulin plus nightly oral antihyperglycemic agent
D. Stop all antihyperglycemic agents while patient is in
the hospital, monitor the glucose level, and use an
all-insulin regimen if required
Should Oral Hypoglycemic Drugs Be
Discontinued During Hospitalization?
• Insulin is cornerstone of in-patient glycemic management
• Usually oral medications are discontinued
upon hospitalization because:
– Difficult to titrate
– Patients may be NPO
– Contraindications may exist during acute illness
•
e.g. metformin and renal impairment, use of contrast media;
TZDs and heart failure
NPO = nothing by mouth; TZDs = thiazolidinediones.
What Comes First Upon Hospital Admission?
• Insulin strategies that are
– Familiar to both providers and nurses in multiple clinical areas
– Consistent with usual hospital practice (e.g. addresses sudden
NPO status, the variability of critical illness, and meal schedule)
– Evidence based
– Flexible enough to allow for optimal safety and individualized
care
– Not tailored to the home environment (because the hospital is
not home)
Polling Question 7
Activity Survey
The patient is ready to be discharged. What is the optimal
antihyperglycemic regimen for this patient on discharge?
A. Keep patient on the all-insulin in-hospital regimen
B. Place patient on the regimen she was on prior to
hospitalization - glipizide 10mg twice daily, pioglitazone
45mg
C. Place patient on insulin glargine plus meal-time insulin
D. Place the patient on a DPP-4 inhibitor
ADA/EASD General Recommendations for Hyperglycemia Management
Healthy eating, weight control, increased physical activity & diabetes education
Monotherapy
Metformin
Efficacy*
Hypo risk
Weight
Side effects
Costs
high
low risk
neutral/loss
GI / lactic acidosis
low
If HbA1c target not achieved after ~3 months of monotherapy, proceed to 2-drug combination (order not meant to denote
any specific preference - choice dependent on a variety of patient- & disease-specific factors):
Metformin
Dual
therapy†
Efficacy*
Hypo risk
Weight
Side effects
Costs
+
Metformin
+
Metformin
Metformin
+
Metformin
+
+
Metformin
+
Sulfonylurea
Thiazolidinedione
DPP-4
inhibitor
SGLT2
inhibitor
GLP-1 receptor
agonist
Insulin (basal)
high
moderate risk
gain
hypoglycemia
low
high
low risk
gain
edema, HF, fxs
low
intermediate
low risk
neutral
rare
high
intermediate
low risk
loss
GU, dehydration
high
high
low risk
loss
GI
high
highest
high risk
gain
hypoglycemia
variable
If HbA1c target not achieved after ~3 months of dual therapy, proceed to 3-drug combination (order not meant to denote
any specific preference - choice dependent on a variety of patient- & disease-specific factors):
Metformin
+
Triple
therapy
Sulfonylurea
+
TZD
Metformin
+
Thiazolidinedione
+
Metformin
Metformin
+
+
DPP-4
Inhibitor
+
SU
SGLT-2
Inhibitor
+
SU
SU
Metformin
+
GLP-1 receptor
agonist
+
Metformin
+
Insulin (basal)
+
TZD
SU
or
DPP-4-i
or
DPP-4-i
or
TZD
or
TZD
or
TZD
or
DPP-4-i
or
SGLT2-i
or
SGLT2-i
or
SGLT2-i
or
DPP-4-i
or
Insulin§
or
SGLT2-i
or
Insulin§
or
Insulin§
or GLP-1-RA
or GLP-1-RA
or
or
Insulin§
or GLP-1-RA
Insulin§
If HbA1c target not achieved after ~3 months of triple therapy and patient (1) on oral combination, move to injectables, (2) on GLP-1 RA, add
basal insulin, or (3) on optimally titrated basal insulin, add GLP-1-RA or mealtime insulin. In refractory patients consider adding TZD or SGL T2-i:
Metformin
Combination
injectable
therapy‡
+
Basal Insulin +
Inzucchi SE et al. Diabetes Care. 2015;38:140-149.
Mealtime Insulin or
GLP-1-RA
GLP = glucagon-like peptide; DPP4 = Dipeptidyl peptidase-4
Renal Impairment: Proceed with Caution
• Metformin: contraindicated when eGFR <30, • SGLT-2 inhibitors
not recommended when eGFR between 30– Canagliflozin (100-300mg QD): 100 mg QD
45
for eGFR 45-<60; discontinue (or do not
initiate) when eGFR <45; contraindicated
• SU: dose reduction or replacement for renal
when eGFR<30
insufficiency; do not use glyburide
• Insulin: dose reduction for renal insufficiency
• GLP-1 receptor agonists
– Exenatide: do not use if eGFR <30
– Others: use with caution
• DPP-4 inhibitors
– Sitagliptin (100 mg QD): 50 mg for eGFR <50,
25 mg for eGFR <30
– Saxagliptin (5 mg QD): 2.5 mg QD when
eGFR <50
– Linagliptin (5 mg QD): no dose adjustment
needed
– Alogliptin (12.5 mg QD): 6.25 mg QD for CrCl
<30 mL/min
– Dapagliflozin (10 mg QD): do not initiate when
eGFR <60; discontinue when eGFR
persistently <60; contraindicated in severe
renal impairment, ESRD, dialysis
– Empagliflozin (10-25 mg QD): do not initiate
when eGFR <45; discontinue when eGFR
persistently <45; contraindicated in severe
renal impairment, ESRD, dialysis
Physicians' Desk Reference. Montvale, NJ: PDR Network; 2014; FDA. Available at: www.fda.gov/Drugs/DrugSafety/ucm493244.htm.
Impact of Renal Insufficiency on
SGLT-2 Inhibitor Efficacy
Canagliflozin (day 10 at 20 mg/day)
Efficacy: UGE
(% of Normal)
0
-50
-100
Mild RI (eGFR 60-90)
-42%
Moderate RI (eGFR 30-59)
-80%
Severe RI (eGFR 15-29)
-90%
• Exposure was increased by 39% to 200% of normal with progressively greater
renal impairment
• Post hoc analysis of moderate renal impairment group
– Greater A1c reduction (-0.33% to -0.37%) in patients with eGFR 45-59 vs patients with
eGFR 30-44 (0.05% to 0.07%)
– No changes significantly different from PBO
US FDA briefing document: dapagliflozin. Available at: www.fda.gov/downloads/AdvisoryCommittees/
CommitteesMeetingMaterials/Drugs/EndocrinologicandMetabolicDrugsAdvisoryCommittee/UCM262994.pdf.
When to Avoid a Class
Class
Metformin
Contraindications and Warnings
Renal disease or dysfunction
contraindicated when eGFR <30
not recommended when eGFR between 30-45
Hypoglycemia
Sulfonylureas
Glitazone
-Glucosidase
inhibitors
renal impairment:
glyburide not recommended if CrCl <50 mL/min
glipizide not recommended if CrCl <10 mL/min
avoid glyburide in older adults due to prolonged action
Heart failure and fracture, in women with osteoporosis
MI (rosiglitazone)
Cirrhosis: inflammatory bowel disease, colonic ulceration, partial intestinal
obstruction (or being predisposed to obstruction), other problems with
digestion or absorption
McDonnell ME. Data on file 2016; Available at: www.fda.gov/Drugs/DrugSafety/ucm493244.htm.
When to Avoid a Class (cont)
Class
Meglitinides
Dipeptidyl peptidase
(DPP) 4 inhibitors
Contraindications and warnings
Patients with several renal insufficiency should initiate therapy with
reduced doses and should be used with caution in patients with impaired liver
function
Pancreatitis History
adjustment needed for most
Pancreatitis history
GLP-1 agonists
SGLT-2 inhibitors
McDonnell ME. Data on file 2016
not recommended in patients with severe renal impairment;
black-box warning advises that the class is contraindicated in patients with a
personal or family history of medullary thyroid carcinoma, or in patients with
MEN 2
Hypotension
avoid in severe renal impairment
monitor for genital infection, bladder cancer, UTI, or ketoacidosis
Case Study 2: Considerations for Discharge
• Osteoporosis
– TZDs increase fracture risk; DISCONTINUE
• Hypoglycemia
– Risk factors: older age, renal insufficiency, significant hospitalization for
hypoglycemia
– Drug classes to avoid: SUs, insulin
• Renal Insufficiency
–
–
–
–
Metformin contraindicated
SGLT-2 inhibitors: not effective
GLP-1 RAs: possible (not exenatide), if weight reduction is also a goal
DPP-4 inhibitors: may require dose adjustment
What is the optimal treatment choice for this patient?
Profiles of Antidiabetic Medications
DPP4-I and GLP1 RA have the
least number of
contraindications for this frail
patient with osteoporosis and
renal impairment
Copyright © 2013 AACE. May not be reproduced in any form without express written permission from AACE.
“Survival Skills” to Be Taught Before Discharge
How and when to take medication/insulin
What to expect from the medication
How/when to test BG (SMBG)
What are target glucose levels
Basics on meal planning
How to treat hypoglycemia
Sick-day management plan
Date/time of follow-up visits
Including diabetes education
When and who to call on the health care team
What community resources are available
Moghissi ES et al. Endocr Pract. 2009;15:353-369.
Transition from Hospital to Out-patient Care
• Preparation for transition to the out-patient setting should
begin at the time of hospital admission
• Clear communication with out-patient providers is critical
for ensuring safe and successful transition to out-patient
management
• Collaboration between the patient and/or significant other
with entire interdisciplinary team is crucial in successful
discharge planning
Umpierrez GE et al. J Clin Endocrinol Metab. 2012;97:16-38.
Available at: www.ntocc.org. Accessed: August 5, 2014.
Polling Question 8
Activity Survey
Your pharmacist can help in transitioning your patient from
hospital to home and reduce readmission by:
A. Prescribing an injectable agent to patients with HbA1c >8%
B. Determining factors that caused admission or readmission
and counsel about medication
C. Discussing medication discontinuation strategies with the
patients when side effects occur
D. All of the above
Multidisciplinary Approach to Managing
In-patient Hyperglycemia across Patient
Transitions
Hospitalist/
Endocrinologist
Nurse
Primary Care Physician
Patients/
Their family
Pharmacist
Hospital
Care Coordinator
Diabetes Educator/Dietitian
Hospital Discharge Transition
From Hospital to Home
• Stabilize blood glucose prior to discharge
• Obtain A1c for discharge planning if result not available
for the previous 2 to 3 months
• Provide in-patient education (survival skills)
• Refer patient for out-patient education
– ADA-recognized education programs (www.diabetes.org)
• Prepare for out-patient follow-up with PCP
– Inform PCP and health care team of new medications and rationales for change
– Utilize the clinical pharmacist for discharge-medication counseling and care coordination
around ensuring prescription access
Magee MF. Hosp Physician. 2006;2:17-28.
Clement S et al. Diabetes Care. 2004;27:553-591.
Inzucchi SE. N Engl J Med. 2006;355:1903-1911.
Hassan E. Am J Health Syst Pharm. 2007;64(10 suppl 6):S9-S14.
Medication Management in Care Transitions
• Pharmacist is uniquely
positioned and qualified to
provide medication
management in care
transitions (MMCT)
• Support medication
adherence by providing
patient-centered medication
management
• Reduce risk of medication
related problems (MRPs)
through care coordination
(discharge planning)
ASHP Intersections. Available at: www.ashpintersections.org/2013/09/hens-offeropportunities-for-pharmacists-to-improve-patient-care. Accessed: 2/20/2016.
Medication Management in Care Transitions
Phase of Care
Admission
During
Hospitalization
Discharge
Home
Role of the Pharmacist
Medication Assessment
at Admission
Determine factors in
admission/readmission
• Medication history
• Medication reconciliation
• Adverse drug events (ADE)
• Medication adherence
• Medication access
Anticipate post-discharge
needs
• Caregiver support
• Barriers to adherence
Optimizing Therapy
Discharge Planning
Provide patient counseling
• Identify barriers to learning
• Medication management
• Disease self-management
• Medication adherence
• Use “Teach Back” method
• Provide tools
Review medication regimen
• Medication reconciliation
• Provide medication list and
related information to:
- Patient/caregiver
- Physician/medical team
- Pharmacy/pharmacist
- Home health nurse
Optimize the medication
regimen
• Initiate indicated medications
(EBM)
• Discontinue unnecessary or
unsafe medications
• Simplify the medication
regimen
Verify appropriate postdischarge care plan
• Ensure plan for medication
access
• Ensure appropriate discharge
follow-up according to need
• Ensure proper information is
provided regarding contact
information, action plan for
care, and symptom or AE
management
Adapted from Washington Patient Safety Coalition. Available at: www.wapatientsafety.org.
Post-Discharge
Medication Management
Contact patient/caregiver
• In person or virtual
encounter
Review patient status and
medication
• Medication reconciliation
• Medication adherence
• ADE monitoring
• Medication access
• Medication management/
disease management
Communicate to other
providers any pertinent
medical information or
findings
Medication Management in Care Transitions
• Medication management is a major component of
advanced discharge planning and transitional care
– More post-discharge adverse events are related to drugs
than other causes
– Lack of adherence to medication prescribed at discharge
has been shown to be a driver of post-discharge adverse
drug events
• $100 billion per year = estimated aggregate cost of hospital
admissions related to medication adherence
Improving Medication Adherence and Reducing Readmissions. The Network for Excellence in Health Innovation
(NEHI). 2012. Available at: www.nacds.org/pdfs/pr/2012/nehi-readmissions.pdf.
Key Take-away Messages
1. Diabetes is a common diagnosis in the hospital setting;
hospitalization provides an opportunity to identify and improve
glycemic control
2. The many transitions of care during hospitalization and back to
the out-patient setting can create challenges to glycemic control
3. A team approach, medication reconciliation, and policies to
manage hyperglycemia and insulin therapy can improve diabetes
care
4. Patients with diagnosed diabetes or newly diagnosed diabetes
may require changes to or intensification of therapy and
appropriate education
CME Credit
•
Post-activity Survey
– Now that the program has completed, please take a
moment to answer the Post-activity Survey questions on
your form
– Your answers are important and will help us identify
remaining educational gaps and shape future CME activities
•
CME Evaluation
– If you’re seeking credit, ensure you’ve filled in your name
and demographic information on page 1 and complete the
CME Evaluation on your form (after the Post-activity Survey)
– Return all forms to on-site CME staff
Thank you for joining us today!