Transcript 15 Pedersen Hypoglycemia Banff Nov 23 2012x

HYPOGLYCEMIA IN DIABETES
Sue Pedersen, MD, FRCPC
Specialist in Endocrinology & Metabolism
C-ENDO Endocrinology Centre, Calgary
Rocky Mountain GIM Conference
Banff, AB
November 23, 2012
1
Disclosures: Sue Pedersen, MD, FRCPC
• Research trials: Novo Nordisk, Boehringer Ingelheim, Sanofi
Aventis, Eli Lilly, Astra Zeneca, BMS, J&J
• Speaking honoraria: Sanofi, Novo Nordisk, Merck, BMS,
Eli Lilly, Astra Zeneca, Roche
• Advisory Boards: Merck, Novo Nordisk, BMS
• Stocks: none
• Slides: some are personal; some have been drawn from slide
decks provided by: Novo Nordisk, Merck, Medtronic, BMS,
Eli Lilly
Objectives
• To examine prevalence and consequences of
hypoglycemia in the diabetic patient
• To review risk factors for hypoglycemia
• To discuss strategies to minimize the incidence
of hypoglycemia
3
Question
Which color of food, plate, and tablecloth
results in the lowest calorie intake?
a) red plate, red food, white cloth
b) white plate, red food, red cloth
c) white plate, red food, white cloth
d) red plate, white food, white cloth
HYPOGLYCEMIA: PREVALENCE
Hypoglycemia is under-recognized
• Patients often underreport hypoglycemia
• Fear of losing licence/employability
• Some think it’s a ‘normal part’ of having
diabetes
• Patient may be hypoglycemia unaware
• Physicians don’t ask about it enough
6
Minor hypoglycemia occurs frequently
and may be under-reported
Proportion of patients with asymptomatic hypoglycemia as measured by
continued glucose monitoring systems:
63%
type 1 diabetes1
47%
type 2 diabetes1
74%
of these
were nocturnal1
83%
54%
type 2 diabetes2
of these were nocturnal2
1. Chico A et al. Diabetes Care. 2003;26(4):1153-1157;
2. Weber KK et al. Exp Clin Endocrinol Diabetes. 2007;115(8):491-494.
Hypoglycemia is common among patients
on insulin therapy
Events per patient per year
Hypoglycemic events per patient per year as recorded over a one-month period1
50
45
40
35
30
25
20
15
10
5
0
42.89
16.37
1.15
0.35
Type 1
Type 2
Overall
Severe
1. Donnelly LA et al. Diabet Med 2005;22:749-755;
2. Alvarez Guisasola F et al. Diabetes Obes Metab. 2008;10(suppl 1):25-32.
% of patients reporting ≥1
hypoglycemic event/year
Hypoglycemia risk increases with the
intensification of therapy
35
32.6%
30
25
21.2%
20
15
10
5
0
7.9%
0.8%
Diet alone
1.7%
MET
SU
Basal
insulin
only
Basal +
bolus
insulin
For all therapies, the significance of
differences between levels is p<0.0001
Wright A et al. J Diabetes Complicat 2006;20:395–401 (UKPDS 73)
Proportion experiencing ≥1 episode of
severe hypoglycemia over 9–12
months
Proportion of patients experiencing severe hypoglycemia
increases as duration of diabetes increases
1.0
Insulin-treated patients
0.8
0.6
0.4
0.2
0.0
Type 2
<2 years
Type 2
>5 years
Type 1
<5 years
Type 1
>15 years
Diabetologia. 2007;50:1140–7.
10
HYPOGLYCEMIA: CONSEQUENCES
Severe hypoglycemia increases the risk for
adverse outcomes
Hazard ratios represent the risk of an adverse cardiovascular outcome or
death among patients reporting severe hypoglycemia (<2.8 mmol/L)* as
compared with those not reporting severe hypoglycemia
Clinical Outcome and
Interval After Hypoglycemia
Hazard Ratio
(95% CI)†
Microvascular events
2.07 (1.32-3.26)‡
Macrovascular events
3.45 (2.34-5.08)‡
Death from any cause
3.30 (2.31-4.72)‡
Death from non-CV cause
2.86 (1.67-4.90)‡
Death from CV cause
3.78 (2.34-6.11)‡
*Severe
hypoglycemia is defined as blood glucose <2.8 mmol per litre with transient dysfunction of the CNS, without other apparent cause,
during which the patient was unable to administer treatment (requiring help from another person).
†Adjusted for multiple covariates: sex, duration of diabetes, treatment assignment, presence or absence of a history of macrovascular disease,
presence or absence of a history of microvascular disease, and smoking status at baseline. Time-dependent covariates during follow-up included
age; level of glycated hemoglobin; body mass index; creatinine level; ratio of urinary albumin to creatinine; systolic blood pressure; use or
nonuse of sulfonylurea, metformin, thiazolidinedione, insulin, or any other diabetes drug; and use or nonuse of antihypertensive agents.
‡p<0.001.
CI=confidence interval.
Zoungas S. N Engl J Med. 2010;363(15):1410-18.
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Presentation title
Date
Slide no 13
Pathophysiologic Cardiovascular Consequences
of Hypoglycemia
 CRP
 VEGF
 IL-6
Inflammation
 Neutrophil
activation
 Factor VII
 Platelet
activation
Blood coagulation
abnormalities
HYPOGLYCEMIA
Endothelial
dysfunction
 Vasodilation
Sympathoadrenal response
Rhythm abnormalities
Hemodynamic changes
 Adrenaline
Heart rate variability
 Contractility
 Oxygen consumption
 Heart workload
CRP=C-reactive protein; IL-6=interleukin 6; VEGF=vascular endothelial growth factor.
Desouza CV et al. Diabetes Care. 2010;33(6):1389-1394. REFERENCES to note UK Hypoglycaemia Study Group. Risk of hypoglycaemia in
types 1 and 2 diabetes: effects of treatment modalities and their duration. Diabetologia. 2007;50(6):1140-1147. Cryer PE. Hypoglycemia in
Diabetes: Pathophysiology, Prevalence, and Prevention. Alexandria, VA: American Diabetes Association; 2009.
Minor hypoglycemia is significant and
can impact patients’ lives
Lifestyle changes
Rated “sometimes” or “always”
Type 1
n=193
Type 2
n=97
Ate extra food
66.8%
62.9%
Had greater fear of future
hypoglycemia
37.8%
29.9%
Went home from school, work,
activities
6.7%
10.3%
Stayed home the next day
1.6%
9.3%**
*p<0.001, **p<0.01
Leiter, Yale et al. Can J Diabetes 2005; 29(3): 186-192.
Patients rank fear of severe hypoglycemia as highly
as fear of developing serious chronic complications
Very worried
Men
Women
Not worried
“Mild”
hypoglycemia
“Severe”
Thoughts
hypoglycemia about diabetes
Blindness
Kidney
complications
Based on patient (n=411, T1DM) attitudes on hypoglycemia using a visual analog scale.
Pramming S et al. Diabetes Med. 1991;8(3):217-222.
Impact of non-severe hypoglycemic
events on productivity
• Non-severe hypoglycemic events* cost the
individual an estimated 1,939.06 – 2,986.28 US$
per year
• Absenteeism or lost time from work
• Reduced productivity while at work
• Out-of-pocket expenses (e.g. extra groceries,
extra test strips and lancets, transportation
services)
Brod M et al. Value in Health (in press)
16
HYPOGLYCEMIA: RISK FACTORS
2.0
*Based
4.0
Men aged 23 ± 2 years
(n=7)
Hypoglycemic
awareness
3.5
3.0
2.5
Greater
reaction time
for corrective
action
Onset of
cognitive dysfunction
Blood glucose concentration
(mmol/L)
Blood glucose concentration
(mmol/L)
Thresholds for hypoglycemia
vary with age*
4.0
Men aged 65 ± 3 years
(n=7)
3.5
Hypoglycemic
awareness
3.0
Onset of
cognitive dysfunction
Less reaction
time for
corrective
action
2.5
2.0
on data in nondiabetic patients with no family history of diabetes.
Figure adapted from Zammitt NN, Frier BM. Diabetes Care. 2005;28(12):2948-61.
Matyka K et al. Diabetes Care. 1997;20(2):135-41.
18
Relationship between severe
hypoglycemia and hba1c
Incidence per 100 person-years
Severe hypoglycemia correlated to poor
control in intensively treated patients
6
5
4
3
2
1
0
6.0
7.0
8.0
Updated average HbA1c
9.0
Miller ME BMJ. 2010;340:b5444.
19
Risk factors for hypoglycemia
•
•
•
•
•
•
•
•
•
•
•
Older age
Long duration of diabetes
Prior episode of severe hypoglycemia
DM meds used:
• Type of insulin
• Non-insulin medications
Glycemic control – too tight, or very poor
Hypoglycemia unawareness
Delayed/smaller/missed meal
Alcohol
Exercise
Renal dysfunction
Other meds: eg nonselective beta blockers
20
What’s the ideal A1c?
• 35 yo man, T2DM x4 years, metformin 1g bid
• 75yo woman, T2DM x17 years, on metformin and
glyburide
• 55yo man, T2DM x10 years, on metformin and
DPP-4 inhibitor
STRATEGIES TO MINIMIZE
HYPOGLYCEMIA
Type 2 diabetes therapies
Class
Agent
Hypos
Alpha-glucosidase Inhibitors
Acarbose (GlucoBay)
No
Biguanides
Metformin (Glucophage)
No
Linagliptin (Trajenta)
No
Saxagliptin (Onglyza)
No
Sitagliptin (Januvia)
No
Exenatide (Byetta)
No
Liraglutide (Victoza)
No
Analog Insulin
++++
Human Insulin
+++++
Nateglinide (Starlix)
++
Repaglinide (GlucoNorm)
+++
Gliclazide (Diamicron)
++
Glimepiride (Amaryl)
++
Glyburide (Diabeta)
+++
Pioglitazone (Actos)
No
Rosiglitazone (Avandia)
No
DPP-4 Inhibitors
GLP-1R Agonists
Insulins
Relative Risk of Hypoglycemia vs Glyburide
Gliclazide: 0.45*, 0.28
Glimepiride: 0.70, 0.81
Repaglinide: 1.08, 0.81, 0.80, 0.97
Meglitinides
Sulfonylureas
Thiazolidinediones
Gangji AS et al.
Copyright © Canadian Heart Research Centre 2012. This presentation may not be reproduced without written authorization
Diabetes Care 2007; 30(2):389-94
SU mechanism of action
SUs promote insulin release from pancreatic β-cells by
binding to SU receptors and closing ATP-sensitive
potassium (KATP) channels
Pancreatic β-cell
Sulfonylurea
↓
Blood
glucos
e
Kumar: Robbins and Cotran Pathologic Basis of Disease, Professional Edition, 8th ed. 2009.
24
KATP channels are located in various
excitable cell types
• In addition to pancreatic β-cells, KATP channels are
located in other excitable cell types such as:
• Cardiac myocytes
• Vascular smooth muscle cells
• Skeletal muscle cells
• Neurons
Abdelmoneim AS, et al. Diabetes Obes Metab. 2012;14(2):130-138.
25
SUs may block ischemic
preconditioning
• The preconditioned myocardium is
more resistant to ischemic insult1
• SUs close cardiac KATP channels,
potentially blocking ischemic
preconditioning and resulting in a
large infarct1
• The clinical relevance of the effects
of SUs on cardiac KATP channels
remains to be proven2
26
1. Brady PA, Terzic A. J Am Coll Cardiol.
1998;31(5):950-6.
2. Inzucchi SE, et al. Diabetes Care.
2012;35(6):1-16.
Certain sulfonylureas may increase
mortality and CV morbidity
In a Danish study of 107,806 patients,
monotherapy with certain commonly used sulfonylureas
(glimepiride, glibenclamide, glipizide, and tolbutamide) appeared
to be associated with increased mortality and CV risk vs
metformin in both patients with and without previous MI.
No Previous MI
Previous MI
Schramm TK, et al. Eur Heart J. 2011;32:1900-1908
CV, cardiovascular; MI, myocardial
infarction.
27
Increased mortality with SU may be
dose related
In a Canadian retrospective cohort study of patients with newly
diagnosed T2DM (n=12,272), first- or second-generation
sulfonylurea monotherapy was associated with increased mortality
in a dose-related manner.
All-cause Mortality
a
aEither
chlorpropamide or tolbutamide.
Simpson SH, et al. CMAJ. 2006;174:169-74.
T2DM, type 2 diabetes mellitus.
28
SU tissue selectivity:
in vitro studies
SU
Tissue Selectivity
Gliclazide
Pancreas-selective
Glipizide
Pancreas-selective
Tolbutamide
Partial pancreas-selective
Glimepiride
Non-selective
Glyburide (glibenclamide)
Non-selective
• Non-selective SUs may inhibit ischemic
preconditioning, possibly translating into increased
CV risk
29
Abdelmoneim AS, et al. Diabetes Obes Metab. 2012;14(2):130-138.
GLP-1 actions are glucose-dependent
in patients with T2DM
Fasting glucose
mmol/l
mg/dL
250
15.0
12.5
200
10.0
7.5
5.0
*
Insulin
Glucagon
pmol/l
*p<0.05
n=10
150
*
*
*
*
*
Infusion
pmol/l 250
100
*
50
mUl/l
40
200
30
150
20
100
50
*
Placebo
GLP-1
*
*
*
*
*
10
0
*
20
15
*
10
*
*
*
5
0
60
120
180
240
Nauck MA, et al. Diabetologia. 1993;36:741–744.
DPP-4 Inhibitors: Current safety
analysis – cardiovascular events
No increased risk of CV events was observed in patients
randomly treated with DPP-4 inhibitors
DPP-4 inhibitor better
Alogliptin5,†
0.21
Total patients in
analysis
Comparator better
Primary
endpoint
3,489
Non-fatal MI, non-fatal
stroke, CV death
Pre-specified/
Independent
adjudication
5,239
CV death, MI, stroke,
hospitalisation due to angina
pectoris
Pre-specified/
independent
adjudication
4,607
MI, stroke, CV death
Pre-specified/
Independent
adjudication
10,246
Med DRA terms
for MACE
No formal adjudication
10,988
Acute coronary syndrome,
transient ischaemic attack,
stroke, CV death
Pre-specified/
Independent
adjudication
1.19
0.63
Comments
Linagliptin1
0.15
Saxagliptin4
0.23
Sitagliptin2
0.34
0.74
0.42
0.41
Vildagliptin3,†
0.80
0.68
1.12
0.62 0.84 1.14
1/8
1/4
1/2
1
2
Risk ratio for major CV events1-5
4
8
Johansen O-E., et al. ADA 2011 Late breaker 30-LB; 2 Williams-Herman D, et al. BMC Endocr Disord. 2010;10:7.; 3 Schweizer A, et
al. Diabetes Obes Metab. 2010;12(6):485–494;
4 Frederich R, et al. Postgrad Med. 2010;122(3):16–27; 5 White et al. 2010, ADA Scientific Sessions. Abstract 391-PP.;
†Investigational agents, not available in Canada
1
31
Exenatide bid: RRs and 95% CIs Were
Consistent Across Multiple Methods of Analysis
Endpoint/ Method
RR
(95% CI)
0.70
(0.38,
1.31)
0.71
(0.36,
1.37)
0.69
(0.39,
1.25)
0.78
(0.42,
1.47)
0.53
(0.21,
1.35)
0.69
(0.46,
1.03)
0.68
(0.44,
1.04)
Primary MACE
RR (Mantel-Haenszel)
HR (Cox)
HR (Andersen-Gill)
RR (Pooled)
RR (Shuster)
Exenatide Better
Comparator Better
Secondary CV
endpoint
RR (Mantel-Haenszel)
HR (Cox)
HR (Andersen-Gill)
0.69
RR (Pooled)
0.77
RR (Shuster)
0.44
(0.47,1.01
)
•
(0.51,
1.17)
0.0
0.5
1.0
1.3
1.5
(0.22,
0.86)
Ratner R, et al. Cardiovasc Diabetol 2011
1.8
2.0
Liraglutide: Adjudicated MACE
IR
95% CI
SMQ, Broad
0.73
(0.38; 1.41)
39
SMQ, Narrow
0.73
(0.38; 1.41)
39
Custom
0.72
(0.35; 1.50)
31
0.1
1
Incidence ratio
Marso et al. Diab Vasc Dis Res 2011;8:237-40
10
Number
of events
What Type of Insulin to Use?
Basal
Mealtime
Insulin action
Breakfast
4:00
Lunch
8:00
12:00
16:00
Time
Dinner
20:00
24:00
4:00
8:00
Analogue insulin more closely matches physiologic insulin profiles.
A long-acting insulin analogue (detemir, glargine)* may
be considered as an alternative to NPH as the basal insulin.
Rapid-acting insulin analogues should be considered over regular insulin.
*Grade B, Level 2 (17-20) (to reduce the risk of hypoglycemia) Grade B, Level 2 (50), for detemir; Grade C, Level 3 (51), for
glargine.
Adapted from Levemir®, NovoRapid®, NovoMix®30 Product Monographs, Novo Nordisk Canada Inc. 2011.
Owens DR, et al. Lancet. 2001;358:739-46.
34
Short acting analogs vs Regular
• Little (T1) to no (T2) significant effect on
HbA1C
• Benefit to reduce severe hypos in T1DM
• QOL improvements: more convenient, flexible
and with less need for snacks
• No hard outcome data
Singh SR et al CMAJ 2009;180:385-397
Plank J et al Arch Intern Med 2005;165:13371344
Long acting analogs
• Meta analyses of poor quality, and mostly short term studies
• Glycemic control: little benefit compared to conventional
insulin (N or NPH)
• Benefit to reduce hypoglycemia and improve QOL
• Hard outcome data is needed
• Consider whether overnight coverage vs 24h basal coverage
is needed
Singh SR et al CMAJ 2009;180:385-397
Monami M et al Diab Res Clin Pract
2008;81:184-189
Novel basal insulin: Degludec
Characteristics of an ideal basal insulin:
•
Flat, peakless time-action profile
•
Continuous insulin action over a 24 h period
•
Low variability for a predictable metabolic effect
Adapted from: Clore and Thurby-Hay Curr Diab Rep. 2004 4:342-5
Duration of action of basal insulins
NPH
Insulin detemir
Insulin glargine
Up to 12 hour duration
Up to 24 hour duration
2 to 3 times daily
Any time of day,
same time daily
1 to 2 times daily
Any time of day,
same time daily
1 time daily
Any time of day, with possibility to change time daily, if needed
Insulin degludec
42 hour duration of action
T2DM: A1C over time
8.6
70
8.4
68
8.2
Degludec OD (n=744)
glargine OD (n=248)
66
64
7.8
62
7.6
60
7.4
Treatment difference:
Non-inferior
7.2
58
56
7.0
6.8
0.0
0
54
4
8
12
16
20 24 28
Time (weeks)
32
36
40
44
48
Mean±SEM; FAS; LOCF
Comparisons: Estimates adjusted for multiple covariates
In the following results presentations, p-values are shown for results that show statistically
significant differences, and not for results that are statistically insignificant
Garber A et al. Lancet 2012;379:1498-1507
52
HbA1C (mmol/mol)
HbA1c (%)
8.0
T2DM: Confirmed hypoglycemia
Confirmed hypoglycaemia
(cumulative events per patient)
IDeg OD (n=753)
IGlar OD (n=251)
Degludec OD (n=753)
Glargine OD (n=251)
18% risk
reduction,
p=0.036
significant
Time (weeks)
SAS
Comparisons: Estimates adjusted for multiple covariates
Garber A et al. Lancet 2012;379:1498-1507
Nocturnal confirmed hypoglycaemia
(cumulative events per 100 patients)
T2DM: Nocturnal confirmed hypoglycemia
Degludec OD (n=753)
glargine OD (n=251)
25% risk
reduction,
p=0.04
significant
Time (weeks)
SAS
Comparisons: Estimates adjusted for multiple covariates
Garber A et al. Lancet 2012;379:1498-1507
T2DM: Hypoglycemic episodes
Estimated rates of
hypoglycemia
(events/patient yr)
IDeg
(n=753)
IGlar
(n=251)
Severe*
0.06
0.05
Overall Confirmed
11.09
13.63
0.82
Nocturnal
1.39
1.84
0.75
*Insufficient episodes for statistical assessment.
Rate: rate of hypoglycaemia in episodes per patient-year
RR: rate ratio for IDeg OD/IGlar OD
Garber A et al. Lancet 2012;379:1498-507
RR
[0.69-0.99]
[0.58-0.99]
T1DM: Hypoglycemic episodes
Estimated rates of
hypoglycemia
(events/patient yr)
IDeg
(n=472)
IGlar
(n=154)
RR
Severe hypoglycemia
0.21
0.16
1.38[0.72-2.64]
Overall confirmed hypoglycemia 42.54
40.18
1.07[0.89-1.28]
Diurnal confirmed hypoglycemia 36.09
32.82
1.11[0.91-1.34]
Nocturnal
5.86
0.75 [0.590.96]*
4.41
Heller S et al. Lancet 2012;379:1489-97
Flexible timing of dose schedule
Mon
Tue
Wed
Thu
8h
morning
Sun
morning
40h
evening
Sat
8h
morning
40h
Fri
24h
40h
evening
evening
evening
Meneghini L et al. ADA 2011;35-LB
(NN1250-3668).
Key findings through 26 weeks:
Flexible dosing of insulin degludec vs.
once-daily insulin glargine (type 1)
A1C
FPG
Nocturnal
hypoglycemia
rate
Confirmed
hypoglycemia
rate
Insulin
degludec
(FLEX)
-0.4%
-1.3 mmol/L
623
8238
Insulin
glargine
-0.6%
-1.3 mmol/L
996
7973
Treatment difference
[95% CI]
0.17 [0.04-0.30]
Treatment difference
[95% CI]
-0.05 [-0.85-0.76]
Treatment ratio
[95% CI]
0.60[0.44-0.82]
Treatment ratio
[95% CI]
1.03[0.85-1.26]
Comparable
Comparable
40% risk
reduction
Comparable
Type 1
Conclusion
All in comparison with insulin glargine; Red box indicates statistical significance;
hypoglycemia rates presented as rates per 100 patient years of exposure;
Russell-Jones et al. ADA 2012. 348-OR.; Mathieu et al. ADA 2012. Abstract 2162-PO.
Key findings through 26 weeks:
Flexible dosing of insulin degludec vs.
once-daily insulin glargine (type 2)
Confirmed
hypoglycemia
rate
A1C
FPG
Nocturnal
hypoglycemia
rate
Insulin
degludec
(FLEX)
-1.2%
-3.2 mmol/L
63
364
Insulin
glargine
-1.2%
-2.8 mmol/L
75
348
Treatment difference
[95% CI]
-0.42 [-0.82 -0.02]
Treatment ratio
[95% CI]
0.77 [0.44;1.35]
Treatment ratio
[95% CI]
1.03 [0.75;1.40]
Degludec
statistically
better
23% risk
reduction
Comparable
Type 2
Treatment difference
[95% CI]
0.04 [-0.12; 0.20]
Conclusion
Comparable
All in comparison with insulin glargine; Red box indicates statistical significance; hypoglycemia rates
presented as rates per 100 patient years of exposure; Meneghini L et al. ADA 2011;35-LB (NN1250-3668).
Summary – Degludec
• Longer acting basal insulin than currently
available basal insulin analogues
• Lower risk of hypoglycemia, particularly
nocturnal
• Allows more flexibility in dosing regimen
SGLT-2 Inhibitors
180g glucose
filtered
each day
Glomerulus
SGLT2:
up to ~90%* of glucose
is reabsorbed from the
S1/S2 segments
Proximal
tubule
SGLT1:
~10%* of glucose
is reabsorbed from the
S3 segment
*based on animal
data
Excretion:
minimal glucose
Wright, EM. Am J Physiol Renal Physiol. 2001;280:F10–8; Lee ,YJ et al. Kidney Int Suppl. 2007;106:S27–35.
Brown, GK. J Inherit Metab Dis. 2000;23:237–46.
50
732HQ10NP027
Glipizide vs Dapagliflozin: A1C
Mean baseline HbA1c
7.72%
0
Dapagliflozin*
+ metformin
(n=400)
Glipizide†
+ metformin
(n=401)
−0.52
−0.52
-0.1
-0.2
Change in
HbA1c
(%)‡
-0.3
-0.4
-0.5
-0.6
-0.7
Non-inferior mean difference, 0.0%; 95% CI
−0.11% to 0.11%
Nauck M, et al. Diabetologia
2010;53(Suppl 1):S107.
Glipizide vs Dapagliflozin:
Change in Body Weight
Dapagliflozin + metformin
(n=400)
Glipizide + metformin (n=401)
Difference
−4.7 kg
95% CI: −5.1 to −4.2
p<0.0001
2
35%
1.4
1
Weight
change
(kg)*
-1
-2
33.3%
10%
−3.2
-4
*Data are adjusted mean change from
baseline
†Data
30%
Proportion 25%
of patients
with weight 20%
reduction
15%
≥5%†
0
-3
p<0.0001
are adjusted percent
5%
0%
2.5%
Nauck M, et al. Diabetologia
2010;53(Suppl 1):S107.
Glipizide vs Dapagliflozin:
Hypoglycemia by 52 Weeks
50%
p<0.0001
40%
40.8%
Proportion of
patients
30%
with ≥1 episode
of hypoglycemia
by 52 weeks* 20%
10%
0%
*Data are adjusted percent
3.5%
Dapagliflozin Glipizide
+ metformin
+ metformin
(n=400)
(n=401)
Nauck M, et al. Diabetologia.
2010;53(Suppl 1):S107
Pump therapy with continued glucose
monitoring is an emerging, effective option
Impact on A1C of insulin pump therapy with CGM and SMBG
vs. insulin pump therapy and SMBG alone
No increased risk of major hypoglycemia noted with insulin
pump therapy + continued glucose monitoring
Szypowska A et al. European Journal of Endocrinology 2012:567-74.
Emerging closed loop external pancreas technology
Median time spent in normal glucose range:
85% overnight closed-loop session
vs. 27% homecare open-loop session
Hypoglycemia:
No hypoglycemia occurred during closed-loop session.
In development:
Glucose-responsive basal insulins
•
Basal insulin that releases insulin in response to glucose
levels
•
Automatically adjusts to unanticipated changes in blood
glucose levels (i.e. during illness, exercise, etc.)
•
Potential advantages:
•
•
Improved control of prandial glucose excursions
•
Adjustment to early morning increase in hepatic
•
Lower risk of hypoglycemia and hyperglycemia due to fever,
exercise, stress, etc.
Proof-of-concept demonstrated in vitro and in vivo
Biodel Shareholder Presentation, July 12th, 2010. Available at:
http://files.shareholder.com/downloads/BIOD/0x0x386329/80BF35D5-ABB9-4762-ADB8DEBFA0A5ECE1/Biodel_CRS_Smart_Basal__NK_071210.pdf; JDRF Press release, October 22ne, 2008. Available at:
http://www.jdrf.org/index.cfm?page_id=111057; Simon ACR et al. Diabetes, Technology & Therapeutics 2011;S103-8.
CONCLUSIONS
• Hypoglycemia is frequent, often overlooked,
and is associated with adverse outcomes
• Risk factors for hypoglycemia should be
considered when selecting the best treatment
option for our patient
• Several strategies exist to minimize the risk of
hypoglycemia, with new developments on the
horizon
57
Question
Which color of food, plate, and tablecloth
results in the lowest calorie intake?
a) red plate, red food, white cloth
b) white plate, red food, red cloth
c) white plate, red food, white cloth
d) red plate, white food, white cloth
Presentation title
THANK YOU!
Date
Slide no 59