Dr. Khaled [email protected] Hypoglycemia Among Type 2 Diabetics Fasting Ramadan Dr. Khaled Tayeb [email protected]

Hypoglycemia Among Type 2 Diabetics

Fasting Ramadan

Dr. Khaled Dr. Khaled Tayeb

[email protected] [email protected]

To Fast during the month of Ramadan-Prayer and supplication to God-Discipline to be observed during the

month-Rights of property to be respected

ا ك�تب� ( 183) ي�ام� ك�م� � ك�تب� ع�ل�ي�ك�م� الص� ن�وا ا ال!ذين� آم� �ي#ه� ي�ا أون� ب�لك�م� ل�ع�ل!ك�م� ت�ت!ق� ع�ل�ى ال!ذين� من ق�

و� ع�ل�ى 184)

ا أ� ريض. نك�م م! م�ن ك�ان� م ع�د�ود�ات2 ف� ا م! �ي!ام. ( أد�ي�ة6 ون�ه� ف ر� و�ع�ل�ى ال!ذين� ي�طيق� �ي!ام2 أ�خ� عد!ة6 م�ن� أ ر2 ف� ف� س�

أ�ن ي�ر6 ل!ه� و� و� خ� ه� ا ف� ي�ر. م�ن ت�ط�و!ع� خ� كين2 ف� ط�ع�ام� مس�ي�ر6 ل!ك�م� إن ك�نت�م� ت�ع�ل�م�ون� وم�وا� خ� ت�ص�

د.ى 185) آن� ه� ر� يه ال�ق� ان� ال!ذي� أ�نزل� ف م�ض� ر� ر� ه� ( ش�

نك�م� د� م ه م�ن ش� ان ف� ق� ر� ال�ف� د�ى و� ب�ي�ن�ات2 م�ن� ال�ه� ل�لن!اس و�عد!ة6 ر2 ف� ف� و� ع�ل�ى س�

ا أ� ريض. ه� و�م�ن ك�ان� م� م� ل�ي�ص� ر� ف� ه� الش!ر� ر� و�ال� ي�ريد� بك�م� ال�ع�س� ر� ي�ريد� اللOه� بك�م� ال�ي�س� �ي!ام2 أ�خ� م�ن� أل�ع�ل!ك�م� د�اك�م� و� ا ه� � اللOه� ع�ل�ى م� وا لت�ك�ب�ر� � ال�عد!ة� و� ل�وا لت�ك�م و�

ون� ك�ر� ت�ش�

To Fast during the month of Ramadan-Prayer and supplication to God-Discipline to be observed during the

month-Rights of property to be respected

ا ك�تب� ( 183) ي�ام� ك�م� � ك�تب� ع�ل�ي�ك�م� الص� ن�وا ا ال!ذين� آم� �ي#ه� ي�ا أون� ب�لك�م� ل�ع�ل!ك�م� ت�ت!ق� ع�ل�ى ال!ذين� من ق�

و� ع�ل�ى 184)

ا أ� ريض. نك�م م! م�ن ك�ان� م ع�د�ود�ات2 ف� ا م! �ي!ام. ( أد�ي�ة6 ون�ه� ف ر� و�ع�ل�ى ال!ذين� ي�طيق� �ي!ام2 أ�خ� عد!ة6 م�ن� أ ر2 ف� ف� س�

أ�ن ي�ر6 ل!ه� و� و� خ� ه� ا ف� ي�ر. م�ن ت�ط�و!ع� خ� كين2 ف� ط�ع�ام� مس�ي�ر6 ل!ك�م� إن ك�نت�م� ت�ع�ل�م�ون� وم�وا� خ� ت�ص�

د.ى 185) آن� ه� ر� يه ال�ق� ان� ال!ذي� أ�نزل� ف م�ض� ر� ر� ه� ( ش�

نك�م� د� م ه م�ن ش� ان ف� ق� ر� ال�ف� د�ى و� ب�ي�ن�ات2 م�ن� ال�ه� ل�لن!اس و�عد!ة6 ر2 ف� ف� و� ع�ل�ى س�

ا أ� ريض. ه� و�م�ن ك�ان� م� م� ل�ي�ص� ر� ف� ه� الش!ر� ر� و�ال� ي�ريد� بك�م� ال�ع�س� ر� ي�ريد� اللOه� بك�م� ال�ي�س� �ي!ام2 أ�خ� م�ن� أل�ع�ل!ك�م� د�اك�م� و� ا ه� � اللOه� ع�ل�ى م� وا لت�ك�ب�ر� � ال�عد!ة� و� ل�وا لت�ك�م و�

ون� ك�ر� ت�ش�

Recommendations for Management of Diabetes

During Ramadan

Diabetes Care Volume 33, Number 8, August

2010

Major risk associated with Major risk associated with fasting in patients with fasting in patients with

diabetesdiabetes1.1. Hypoglycemia Hypoglycemia

2.2. HyperglycemiaHyperglycemia

3.3. Diabetic ketoacidosisDiabetic ketoacidosis

4.4. Dehydration and thrombosisDehydration and thrombosis

Recommendations for Diabetic Individuals during Ramadan, Diabetes Care , vol 33, num. 8, August2010

HypoglycaemiaHypoglycaemia

• 2 – 4% of mortality in patients 2 – 4% of mortality in patients with type 1 diabetes.with type 1 diabetes.

• Rates of hypoglycaemia are some Rates of hypoglycaemia are some several-fold lower in patients with several-fold lower in patients with type 2 compared with type 1 type 2 compared with type 1 diabetesdiabetes

• Rates being lower in patients with Rates being lower in patients with type 2 diabetes treated with oral type 2 diabetes treated with oral agents.agents.


Categories of risks in patients with Categories of risks in patients with type 1 or type 2 diabetes who fast type 1 or type 2 diabetes who fast

during Ramadanduring Ramadan

1. Very high risk1. Very high risk• Severe hypoglycaemiaSevere hypoglycaemia within the last 3 within the last 3

months prior to Ramadan.months prior to Ramadan.• A history of A history of recurrent hypoglycaemiarecurrent hypoglycaemia..• Hypoglycaemia unawarenessHypoglycaemia unawareness..• Sustained poor glycemic control.Sustained poor glycemic control.• Ketoacidosis within the last 3 months Ketoacidosis within the last 3 months

prior to Ramadan.prior to Ramadan.


Breaking the FastBreaking the Fast

All patients must always and All patients must always and immediately end their fast if:immediately end their fast if:1.1. Hypoglycaemia (blood glucose of Hypoglycaemia (blood glucose of

<60mg/dl).<60mg/dl).2.2. Blood glucose reaches <70 mg in the Blood glucose reaches <70 mg in the

first few hours after the start of the fast, first few hours after the start of the fast, especially if insulin, sulfonylurea drugs, especially if insulin, sulfonylurea drugs, or neglitinide are taken at predawn.or neglitinide are taken at predawn.

3.3. Blood glucose exceeds 300 mg with Blood glucose exceeds 300 mg with symptoms of hyperglycaemia.symptoms of hyperglycaemia.


(4.7 fold)

(7.5 fold)

10

Change in outcome measures during Ramadan in participants receiving both gliclazide and metformin1

0.27

0.92

0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1

Hyp

og

lyca

emic

Eve

nts

per

p

erso

n

8.95

7.75

6.75

7.25

7.75

8.25

8.75

9.25

Hb

A1

c (

%)

Pre-Ramadan Post-Ramadan

Hypoglycaemia in study control group on Metfromin + Gliclazide Ramadan 2008

Int J Clin Pract 2009; 63: 1446–50

Hypoglycemia in Sulphonylurea-Hypoglycemia in Sulphonylurea-Treated Subjects with Type 2 Treated Subjects with Type 2

Diabetes Diabetes Undergoing Ramadan Fasting:Undergoing Ramadan Fasting:A Five-Country Observational A Five-Country Observational

StudyStudy

Current Medical Research & Opinion Vol. 27, No. 6, 2011, 1237-1242

ObjectivesObjectives

• To determine the incidence of To determine the incidence of hypoglycemia during Ramadan in hypoglycemia during Ramadan in Muslim subjects with type 2 diabetes Muslim subjects with type 2 diabetes treated with a sulphonylurea.treated with a sulphonylurea.


Subjects & MethodsSubjects & Methods• Eligible subjectsEligible subjects

• Muslim patients with type 2 diabetes Muslim patients with type 2 diabetes treated with Sulphonylureastreated with Sulphonylureas( Glimiperide, ( Glimiperide, Glyclazide , or Glibenclamide)Glyclazide , or Glibenclamide)

• With or without MetforminWith or without Metformin• Age ≥ 18 years oldAge ≥ 18 years old

• Excluded subjects Excluded subjects • Patients with Type 1 diabetesPatients with Type 1 diabetes• Patients with Insulin treated type 2 Patients with Insulin treated type 2

diabetesdiabetes


• Subjects were recruited from 5 Subjects were recruited from 5 countries.countries.

• 300 subjects were selected per country.300 subjects were selected per country.• Diabetes Center in Holy Makkah and Diabetes Center in Holy Makkah and

other centers from (UAE, India, other centers from (UAE, India, Malaysia, and occupied Palestine ).Malaysia, and occupied Palestine ).

Subjects & MethodsSubjects & Methods


Subjects & MethodsSubjects & MethodsPatients were given a daily dairy card to record ..Patients were given a daily dairy card to record ..• any hypoglycemic symptoms and complicationsany hypoglycemic symptoms and complications• The time from the start of hypoglycemic The time from the start of hypoglycemic

symptoms and the last meal and medicationssymptoms and the last meal and medications• Self monitor blood glucoseSelf monitor blood glucose• Need for assistance to treat hypos.Need for assistance to treat hypos.• The fasting was broken or not.The fasting was broken or not.• Cards to be filled daily regardless of symptomsCards to be filled daily regardless of symptoms


Subjects & MethodsSubjects & Methods

• The hypoglycemic events were further The hypoglycemic events were further classified into..classified into..

-- Symptomatic : Symptomatic : (headache, sweating, (headache, sweating, tremors, palpitation, etc..)tremors, palpitation, etc..)

-- Documented: symptomatic with BG ≤ 70 Documented: symptomatic with BG ≤ 70 mg/dl.mg/dl.

-- Severe: requiring medical or non- Severe: requiring medical or non- medical medical

assistance. assistance.


Patients Characteristic in Patients Characteristic in the Studythe Study

Glimepiride (n=428)

Gliclazide (n=386)

Glibenclamide (n=535)

Glipizide (n=29)

Overall(N=1378)

Gender M229 (54 %)225 (58 %)263 (49 %)12 (41 %)729 (53 %)

Age at baseline, yrs

51.4 ± 10.153.7 ± 9.255.5 ± 10.058.1± 9.853.8 ± 10.0

BMI, kg/m228.4 ± 5.229.0 ± 5.329.4 ± 10.045.0 ± 18.546.6 ± 9.9

Age at diabetes diagnosis, yrs

45.3 ± 9.646.9 ± 8.947.5 ± 10.045.0 ± 18.546.6± 9.9


Sulponylurea use by country Sulponylurea use by country in the studyin the study

CountryGlimepiride (n=428)

Gliclazide (n=386)


Glipizide (n=29)

Overall(N=1378)

India239 (56%)50 (13%)107 (20%)0 (0%)396 (29%)

Occupied Palestine48 (11%)0 (0%)170 (32%)29 (100%)247 (18%)

Malaysia 29 (7%)182 (47%)144 (27%)0 (0%)355 (26%)

Saudi Arabia108 (25%)141 (37%)114 (37%)0 (0%)363 (26%)

UAE4 (1%)13 (3%)0 (0%)0 (0%)17 (1%)


ResultsResults• The daily dairy card were returned by 1378 The daily dairy card were returned by 1378

patients from total 1397 patients.patients from total 1397 patients.• Symptomatic hypoglycemia was 40% in Symptomatic hypoglycemia was 40% in

occupied Palestine and 10% in Saudi Arabia occupied Palestine and 10% in Saudi Arabia • Over all symptomatic hypoglycemic events Over all symptomatic hypoglycemic events

were recorded in 271 subjects were recorded in 271 subjects (19.7%)(19.7%)• Headache represent 14.5%, sweating Headache represent 14.5%, sweating

10.2%, tremors 8.5% and palpitation 7%.10.2%, tremors 8.5% and palpitation 7%.


Incidence of symptomatic Incidence of symptomatic hypoglycemia during hypoglycemia during

Ramadan by countriesRamadan by countriesCountries N of Patients

Occupied Palestine 40%

Malaysia24%

United Arab Emirates18%

India13%

Saudi Arabia10%Current Medical Research & Opinion Vol. 27, No. 6, 2011, 1237-1242

Incidence of hypoglycemia Incidence of hypoglycemia during Ramadan by typeduring Ramadan by type

Type of hypoglycemiaPercentage (%)

Symptomatic hypoglycemic events86

Documented hypoglycemic events3.6

Severe hypoglycemic events3.7

Severe hypoglycemic events requiring medical assistance

6.7


Incidence of hypoglycemia Incidence of hypoglycemia during Ramadan by typeduring Ramadan by type

0

20

40

60

80

100

Symptomatic hypoglycemic

events

Documented hypoglycemic

events

Severe hypoglycemic

events

Severe hypoglycemic

events requiring medical assistance

86%

3.6% 3.7% 6.7%

Type of hypoglycemia

Incidence of hypoglycemia Incidence of hypoglycemia during during

Ramadan by types of drugRamadan by types of drug

N of patients (%)Glimepiride (n=428)

Gliclazide (n=386)


Glipizide (n=29)

Overall(N=1378)

Symptomatic hypoglycemic events72 (16.8%)54 (14 %)137 (25.6%)8 (27.6%)271

19.7%

Documented hypoglycemic events17 (4.0%)11 (2.8%)21 (3.9%)0 (0.0%)49

3.6%

Severe hypoglycemic events22 (5.1%)10 (2.6%)58 (10.8%)2 (6.9%)92

6.7%

Severe hypoglycemic events requiring medical assistance

10 (2.3%)6 (1.6%)36 (6.5%)0 (0.0%)51 3.7%


ResultsResults

• Symptomatic hypoglycemia events 1095Symptomatic hypoglycemia events 1095

• Documented hypoglycemic events were similar Documented hypoglycemic events were similar

across all sulphonylurea groups 3.6%, .across all sulphonylurea groups 3.6%, .

• Events not requiring medical assistance 3.7% Events not requiring medical assistance 3.7%

• Events requiring assistance 6.7% .Events requiring assistance 6.7% .

• Subjects experienced a serious complication Subjects experienced a serious complication

1.2% .1.2% .


DiscussionDiscussion• The incidence of severe hypoglycemia requiring The incidence of severe hypoglycemia requiring

medical or non medical assistance or hospitalization medical or non medical assistance or hospitalization

were less than other studies.were less than other studies.

• In the EPIDAR study, 2% of patients hospitalized in In the EPIDAR study, 2% of patients hospitalized in

comparison to 0.5% in this study. (comparison to 0.5% in this study. (Diabetes Care 2004; Diabetes Care 2004;

2306-11)2306-11)

• Health care resources utilization, was less in this Health care resources utilization, was less in this

study. The less severe hypoglycemia events or better study. The less severe hypoglycemia events or better

education regarding the symptoms could explain this.education regarding the symptoms could explain this.


The incidence of Hypoglycaemia in The incidence of Hypoglycaemia in Muslim Type 2 Diabetics treated with Muslim Type 2 Diabetics treated with Sitagliptin or a Sulphoylurea during Sitagliptin or a Sulphoylurea during

Ramadan.Ramadan.

AimAim

• To compare the incidence of To compare the incidence of symptomatic hypoglycaemia with symptomatic hypoglycaemia with

Sitagliptin or A Sulphonylurea during Sitagliptin or A Sulphonylurea during Ramadan.Ramadan.


Patients and study designPatients and study design

• A prospective, open-label, randomised study.A prospective, open-label, randomised study.• 6 countries, 43 clinical sites.6 countries, 43 clinical sites.• 1243 patients of whom 1066 randomized to 1243 patients of whom 1066 randomized to treatment.treatment.• Muslim Type 2 diabetics willing to fast Muslim Type 2 diabetics willing to fast Ramadan.Ramadan.• Age : > 18 Yrs.Age : > 18 Yrs.• Treated with a sulphonylurea for at least 3 Treated with a sulphonylurea for at least 3 months before study with or without metformin months before study with or without metformin and had HbA1c < 10%.and had HbA1c < 10%.


Sitagliptin( n = 507 )

Sulphonylurea( n = 514 )

Glibenclamide158 (31%)181 (35%)

Glimepiride189 (37%)178 (35%)

Glicalazide159 (32%)152 (30%)

Monotherapy41 (8%)41 (8%)

Dual ( SU + MET ), n (%)465 (92%)471 (92%)

Duration of SU Therapy* yrs4.04.0

Experienced hypoglycaemia in 3 M before Ramadan

81 ( 16%)76 (15%)

Data are expressed as frequency, n(%) or mean ± standard deviation unless otherwise indicated. *median

Pre-Randomization Treatment


ResultsResults

• 1066 patients randomised, • 1021 enrolled in the study as they

returned at least one complete diary.• Incidence of symptomatic

hypoglycaemic events - Sitagliptin group (5.1%) - Sulphonylurea group (11.9).


Results

0

5

10

15

20

25

Overall Egypt Palestien Jordan Lebanon Saudi Arabia

UAE

*n/N (%) Sitagliptin

*n/N )%( Sulphonylurea

5.1%

11.9%

0%

18.6%

10.3%

22.1%

6.7% 7.1%

9.9%

21.2%

0.5% 0.5%

20.0%20.0%

*no of patients experiencing event /N overall or in each country by treatment. (%) Current Medical Research & Opinion Vol. 27, No. 6, 2011, 1237-1242

Sitagliptin) n = 507 (n ) %( of patients

Experiencing event

Sulphonylurea) n = 514 (

n )%( of patientsExperiencing event

Symptomatic or asymptomatic hypoglycemic events

35 (6.9%) 84 (16.3%)

Severe hypoglycemic events

00

Hypoglycemic events requiring non-medical assistance

1 (0.2%) 3 (0.6%)

Hypoglycemic events requiring medical assistance

00

* Types of hypoglycemic event defined in Methods

Results


Fear of hypoglycemiais a major concern for patients

1 .Pramming S et al. Diabet Med 1991;8:217–222

Not worried Very worried

Male Female

Male Female

Male Female

Blindness

Male Female

Hypoglycaemic Events

X4 increase

• Main aim• To determine the incidence of hypoglycaemic events in 100 Muslim patients

with T2D fasting during Ramadan, who are treated with dual therapy of metformin plus vildagliptin or metformin plus sulphonylurea (SU)

• Primary objectives• the incidence of hypoglycaemic events defined as:

• Any reported symptoms by the patient and/or any blood glucose measurement of less than 3.9 mmol/L (also defined as mild or Grade 1 hypoglycaemia)

• The need for third party assistance (also defined as severe or Grade 2 hypoglycaemia);

• Secondary objectives• the change in weight;• the change in HbA1c levels; and• the treatment adherence during Ramadan.

VECTOR: Results - Hypoglycaemic events )HE( Mean between-group difference in patients who

experienced at least one HE was –41·7% )p = 0·0002(

(7·7% to 7·2%) (7·2% vs 7·3%)

VECTOR: HbA1cVECTOR: HbA1c

The between group difference was −0·6% The between group difference was −0·6% )p = 0·0262()p = 0·0262(

::AdherenceAdherence

Only 1 1 patient in the Vildagliptin group missed at least one dose, compared with 1010 patients in the SU group .

p = 0·0204

* There are an estimated 325,000 Muslims with type 2 diabetes in the UK** Hypoglycemic event (defined as blood glucose < 3.5 mmol ⁄ l with or without symptoms)

References:1. Devendra D et al. Vildagliptin therapy and hypoglycaemia in Muslim type 2 diabetes patients during Ramadan. Int J Clin Pract, October 2009, 63, 10, 1446–1450.

How to Help Patients Fast Safely

• Patient Education Program.• Select more safe drugs.• Adjust dose if needed• Ensure good non – sugar fluid intake.• Avoid heavy physical exercise at

afternoon.• Ensure good calorie distribution.

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Dr. Khaled [email protected] Hypoglycemia Among Type 2 Diabetics Fasting Ramadan Dr. Khaled Tayeb [email protected]