HYPOGLYCEMIA IN DIABETES

Sue Pedersen, MD, FRCPCSpecialist in Endocrinology & MetabolismC-ENDO Endocrinology Centre, Calgary

Rocky Mountain GIM ConferenceBanff, 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 clothb) white plate, red food, red clothc) white plate, red food, white clothd) 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

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.

83% type 2 diabetes2

54% of these were nocturnal2

74% of thesewere nocturnal1

Hypoglycemia is common among patients on insulin therapy

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.

Type 1 Type 20

5

10

15

20

25

30

35

40

45

5042.89

16.37

1.15 0.35

Overall Severe

Eve

nts

pe

r p

ati

en

t p

er

ye

ar

Hypoglycemic events per patient per year as recorded over a one-month period1

0

5

10

15

20

25

30

35

Hypoglycemia risk increases with the intensification of therapy

Wright A et al. J Diabetes Complicat 2006;20:395–401 (UKPDS 73)

% o

f pati

ents

report

ing

≥1

hypogly

cem

ic e

vent/

year

0.8% 1.7%

7.9%

21.2%

32.6%

For all therapies, the significance of differences between levels is p<0.0001

Proportion of patients experiencing severe hypoglycemia increases as duration of diabetes

increases

1.0

Type 2 <2 years

Type 1 <5 years

Type 2 >5 years

Type 1 >15 years

Pro

port

ion

exp

eri

en

cin

g ≥

1 e

pis

od

e

of

severe

hyp

og

lycem

ia o

ver

9–1

2

mon

ths

Insulin-treated patients

0.8

0.6

0.4

0.2

0.0

10

Diabetologia. 2007;50:1140–7.

HYPOGLYCEMIA: CONSEQUENCES

Severe hypoglycemia increases the risk for adverse outcomes

*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.

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)‡

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

12

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.

Pathophysiologic Cardiovascular Consequences of Hypoglycemia

Vasodilation

Neutrophilactivation

Plateletactivation

Factor VII

Blood coagulationabnormalities

VEGF IL-6 CRP

Inflammation

Endothelialdysfunction

Heart rate variability

Hemodynamic changes

Adrenaline

Contractility

Oxygen consumption

Heart workload

Sympathoadrenal response

Rhythm abnormalities

HYPOGLYCEMIA

Presentation titleSlide no 13

Date

Minor hypoglycemia is significant and can impact patients’ lives

Leiter, Yale et al. Can J Diabetes 2005; 29(3): 186-192.

Lifestyle changesRated “sometimes” or “always”

Type 1n=193

Type 2n=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

Patients rank fear of severe hypoglycemia as highly as fear of developing serious chronic 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.

“Mild” hypoglycemia

“Severe”hypoglycemia

Thoughts about diabetes

Blindness Kidneycomplications

Not worried

Very worriedMen

Women

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)

16

Brod M et al. Value in Health (in press)

HYPOGLYCEMIA: RISK FACTORS

Thresholds for hypoglycemia vary with age*

Blo

od

glu

cose c

on

cen

trati

on

(mm

ol/

L)

2.0

2.5

3.0

3.5

4.0

2.0

2.5

3.0

3.5

4.0

Men aged 23 ± 2 years(n=7)

Men aged 65 ± 3 years(n=7)

Hypoglycemic awareness

Greater reaction time for corrective

action

Onset of cognitive dysfunction

Hypoglycemic awareness

Onset of cognitive dysfunction

Less reactiontime for

corrective action

Blo

od

glu

cose c

on

cen

trati

on

(mm

ol/

L)

*Based 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

Incid

en

ce p

er

10

0 p

ers

on

-years

Updated average HbA1c

6

5

4

3

2

1

0

6.0 7.0 8.0 9.0

Severe hypoglycemia correlated to poor control in intensively treated patients

19

Miller ME BMJ. 2010;340:b5444.

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

Relative Risk of Hypoglycemia vs Glyburide

Gliclazide: 0.45*, 0.28Glimepiride: 0.70, 0.81Repaglinide: 1.08, 0.81, 0.80, 0.97

Gangji AS et al. Diabetes Care 2007; 30(2):389-94

Type 2 diabetes therapies

Copyright © Canadian Heart Research Centre 2012. This presentation may not be reproduced without written authorization from the Canadian Heart Research Centre

Class Agent Hypos

Alpha-glucosidase Inhibitors Acarbose (GlucoBay) No

Biguanides Metformin (Glucophage) No

DPP-4 Inhibitors

Linagliptin (Trajenta) No

Saxagliptin (Onglyza) No

Sitagliptin (Januvia) No

GLP-1R AgonistsExenatide (Byetta) No

Liraglutide (Victoza) No

InsulinsAnalog Insulin ++++

Human Insulin +++++

MeglitinidesNateglinide (Starlix) ++

Repaglinide (GlucoNorm) +++

Sulfonylureas

Gliclazide (Diamicron) ++

Glimepiride (Amaryl) ++

Glyburide (Diabeta) +++

ThiazolidinedionesPioglitazone (Actos) No

Rosiglitazone (Avandia) No

SU mechanism of action

24

Kumar: Robbins and Cotran Pathologic Basis of Disease, Professional Edition, 8th ed. 2009.

Pancreatic β-cell

↓ Blood glucos

e

SUs promote insulin release from pancreatic β-cells by binding to SU receptors and closing ATP-sensitive

potassium (KATP) channels

Sulfonylurea

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

25

Abdelmoneim AS, et al. Diabetes Obes Metab. 2012;14(2):130-138.

SUs may block ischemic preconditioning

26

• 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

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

27

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.

Schramm TK, et al. Eur Heart J. 2011;32:1900-1908 CV, cardiovascular; MI, myocardial infarction.

No Previous MI Previous MI

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.

Simpson SH, et al. CMAJ. 2006;174:169-74. T2DM, type 2 diabetes mellitus.

28

All-cause Mortality

a

aEither chlorpropamide or tolbutamide.

SU tissue selectivity: in vitro studies

• 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.

SU Tissue Selectivity

Gliclazide Pancreas-selective

Glipizide Pancreas-selective

Tolbutamide Partial pancreas-selective

Glimepiride Non-selective

Glyburide (glibenclamide) Non-selective

12.5

10.0

7.55.0

15.0

200

150

10050

250

GLP-1 actions are glucose-dependent in patients with T2DM

Fasti

ng

g

lucose

Insu

lin

Glu

cag

on

PlaceboGLP-1

Minutes Nauck MA, et al. Diabetologia. 1993;36:741–744.0 60 120 180 240

15

10

5

20

*p<0.05 n=10

200

150

100

50

250

30

20

10

0

40pmol/l

mmol/l mg/dL

mUl/l

pmol/l

Infusion

* * **

* **

**

* *

**

* * * * *

DPP-4 Inhibitors: Current safety analysis – cardiovascular events

No increased risk of CV events was observed in patients randomly treated with DPP-4 inhibitors

Risk ratio for major CV events1-5

Total patients in analysis

Primaryendpoint CommentsDPP-4 inhibitor better Comparator better

11/21/41/8 2 4 8

5,239 CV death, MI, stroke,hospitalisation due to angina pectoris

Pre-specified/independent adjudication

Linagliptin1

0.340.15 0.74

10,246 Med DRA termsfor MACE

No formal adjudicationSitagliptin2

0.680.41 1.12

10,988 Acute coronary syndrome, transient ischaemic attack, stroke, CV death

Pre-specified/Independent adjudication

Vildagliptin3,†

0.840.62 1.14

4,607 MI, stroke, CV death Pre-specified/Independent adjudication

Saxagliptin4

0.420.23 0.80

3,489 Non-fatal MI, non-fatalstroke, CV death

Pre-specified/Independent adjudication

Alogliptin5,†

0.630.21 1.19

1 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 31

0.0 0.5 1.0 1.5 2.01.3 1.8

Exenatide bid: RRs and 95% CIs Were Consistent Across Multiple Methods of Analysis

Ratner R, et al. Cardiovasc Diabetol 2011

•

Endpoint/ Method RR (95% CI)

Primary MACE

RR (Mantel-Haenszel) 0.70(0.38, 1.31)

HR (Cox) 0.71(0.36, 1.37)

HR (Andersen-Gill) 0.69(0.39, 1.25)

RR (Pooled) 0.78 (0.42, 1.47)

RR (Shuster) 0.53(0.21, 1.35)

Secondary CV endpoint

RR (Mantel-Haenszel) 0.69 (0.46, 1.03)

HR (Cox) 0.68(0.44, 1.04)

HR (Andersen-Gill) 0.69(0.47,1.01)

RR (Pooled) 0.77(0.51, 1.17)

RR (Shuster) 0.44(0.22, 0.86)

Exenatide Better Comparator Better

Liraglutide: Adjudicated MACE

SMQ, Broad

SMQ, Narrow

Custom

Incidence ratio0.1 1 10

0.72 (0.35; 1.50) 31

0.73 (0.38; 1.41) 39

0.73 (0.38; 1.41) 39

IR 95% CI Number of events

Marso et al. Diab Vasc Dis Res 2011;8:237-40

What Type of Insulin to Use?

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.

4:00 16:00 20:00 24:00 4:00

Breakfast

Lunch Dinner

8:0012:008:00Time

Insu

lin a

ctio

nMealtimeBasal

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;180:385-397Plank J et al Arch Intern Med 2005;165:1337-

1344

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 detemirInsulin glargine

Insulin degludec

Up to 12 hour duration 2 to 3 times dailyAny time of day, same time daily

1 to 2 times dailyAny time of day, same time daily

1 time dailyAny time of day, with possibility to change time daily, if needed

Up to 24 hour duration

42 hour duration of action

T2DM: A1C over time

Mean±SEM; FAS; LOCFComparisons: Estimates adjusted for multiple covariatesIn the following results presentations, p-values are shown for results that show statistically significant differences, and not for results that are statistically insignificant

6.8

7.0

7.2

7.4

7.6

7.8

8.0

8.2

8.4

8.6

0 4 8 12 16 20 24 28 32 36 40 44 48 52

HbA

1c

(%)

Time (weeks)

Treatment difference:Non-inferior

0.0

70

68

62

60

58

56

HbA

1C (m

mol/m

ol)

64

66

54

Garber A et al. Lancet 2012;379:1498-1507

Degludec OD (n=744)glargine OD (n=248)

T2DM: Confirmed hypoglycemia

SASComparisons: Estimates adjusted for multiple covariates

18% risk reduction, p=0.036

significant

IDeg OD (n=753)IGlar OD (n=251)

Time (weeks)

Confirm

ed h

ypogly

caem

ia(c

um

ula

tive e

vents

per

pati

ent)

Garber A et al. Lancet 2012;379:1498-1507

Degludec OD (n=753)

Glargine OD (n=251)

T2DM: Nocturnal confirmed hypoglycemia

SASComparisons: Estimates adjusted for multiple covariates

25% risk reduction,

p=0.04

significant

Noct

urn

al co

nfi

rmed h

ypogly

caem

ia

(cum

ula

tive e

vents

per

100

pati

en

ts)

Time (weeks)

Garber A et al. Lancet 2012;379:1498-1507

Degludec OD (n=753)glargine OD (n=251)

T2DM: Hypoglycemic episodes

Estimated rates of hypoglycemia(events/patient yr)

IDeg (n=753)

IGlar(n=251)

RR

Severe* 0.06 0.05

Overall Confirmed 11.09 13.63 0.82[0.69-0.99]

Nocturnal 1.39 1.84 0.75[0.58-0.99]

*Insufficient episodes for statistical assessment.Rate: rate of hypoglycaemia in episodes per patient-yearRR: rate ratio for IDeg OD/IGlar OD

Garber A et al. Lancet 2012;379:1498-507

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 4.41 5.86 0.75 [0.59-0.96]*

Heller S et al. Lancet 2012;379:1489-97

Flexible timing of dose schedule

morning

Mon Tue Wed Thu Fri Sat Sun

morning morning

evening evening evening evening

40h 40h 40h

8h 8h

24h

Meneghini L et al. ADA 2011;35-LB (NN1250-3668).

Nocturnal hypoglycemia

rate

623

996

Treatment ratio[95% CI]

0.60[0.44-0.82]

40% risk reduction

Key findings through 26 weeks:Flexible dosing of insulin degludec vs.

once-daily insulin glargine (type 1)

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.

A1C

Type 1

Insulin degludec (FLEX)

-0.4%

Insulin glargine

-0.6%

Treatment difference[95% CI]

0.17 [0.04-0.30]

Conclusion Comparable

Confirmed hypoglycemia

rate

8238

7973

Treatment ratio[95% CI]

1.03[0.85-1.26]

Comparable

FPG

-1.3 mmol/L

-1.3 mmol/L

Treatment difference[95% CI]

-0.05 [-0.85-0.76]

Comparable

FPG

-3.2 mmol/L

-2.8 mmol/L

Treatment difference[95% CI]

-0.42 [-0.82 -0.02]

Degludec statistically

better

Nocturnal hypoglycemia

rate

63

75

Treatment ratio[95% CI]

0.77 [0.44;1.35]

23% risk reduction

Key findings through 26 weeks:Flexible dosing of insulin degludec vs.

once-daily insulin glargine (type 2)

A1C

Type 2

Insulin degludec (FLEX)

-1.2%

Insulin glargine

-1.2%

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).

Confirmed hypoglycemia

rate

364

348

Treatment ratio[95% CI]

1.03 [0.75;1.40]

Comparable

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

Proximal tubule

GlomerulusSGLT2:

up to ~90%* of glucose is reabsorbed from the

S1/S2 segments

SGLT1:~10%* of glucose

is reabsorbed from theS3 segment

Excretion:minimal glucose

180g glucose filtered

each day

*based on animal data

732HQ10NP027

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

Glipizide vs Dapagliflozin: A1C

-0.7

-0.6

-0.5

-0.4

-0.3

-0.2

-0.1

0

Dapagliflozin*+ metformin

(n=400)

Glipizide†

+ metformin(n=401)

Change in HbA1c (%)‡

Non-inferior mean difference, 0.0%; 95% CI −0.11% to 0.11%

Mean baseline HbA1c 7.72%

−0.52 −0.52

Nauck M, et al. Diabetologia 2010;53(Suppl 1):S107.

−3.2

1.4

-4

-3

-2

-1

0

1

2

33.3%

2.5%0%

5%

10%

15%

20%

25%

30%

35%

Dapagliflozin + metformin (n=400)

Glipizide + metformin (n=401)

Weight change (kg)*

Proportionof patientswith weightreduction ≥5%†

Difference−4.7 kg

95% CI: −5.1 to −4.2p<0.0001

p<0.0001

*Data are adjusted mean change from baseline†Data are adjusted percent

Nauck M, et al. Diabetologia 2010;53(Suppl 1):S107.

Glipizide vs Dapagliflozin: Change in Body Weight

*Data are adjusted percent

0%

10%

20%

30%

40%

50%

Proportion of patients

with ≥1 episode of hypoglycemia

by 52 weeks*

40.8%

3.5%

p<0.0001

Dapagliflozin+ metformin

(n=400)

Glipizide+ metformin

(n=401)

Glipizide vs Dapagliflozin: Hypoglycemia by 52 Weeks

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 vivoBiodel Shareholder Presentation, July 12th, 2010. Available at:

http://files.shareholder.com/downloads/BIOD/0x0x386329/80BF35D5-ABB9-4762-ADB8-DEBFA0A5ECE1/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 clothb) white plate, red food, red clothc) white plate, red food, white clothd) red plate, white food, white cloth

THANK YOU!

Presentation titleSlide no 59

Date