Recommendations for Management of

Diabetes during Ramadan - Update 2015

International Group for Diabetes and Ramadan

IGDR

Most people take two meals (Iftar and Suhur).

Sick people are exempted from the duty of fasting.

Diabetic patients fall in this category because of both acute and chronic

complications.

This is not a simple permission but the prophet Mohammad (POH) said

“God likes his permission to be fulfilled, as he likes his will to be executed”.

Many patients insist on fasting putting a real challenge to the medical system.

Introduction

فمن كان منكم مريضا او على سفر فعدة من ايام أخر

1. Individual decision.

2. Religious practice.

3. Medical opinion.

To fast or not to fast

Religion Medicine

Person

Magnitude of the problem

Prevalence of diabetes: 6.9%

Type 1 diabetes ~ 43% Type 2 diabetes ~ 79%

More than 55 million people with diabetes worldwide fast

during Ramadan.

Results of the epidemiology of diabetes and Ramadan 1422/2001( EPIDIAR) study. Diabetes care 2004;27:2306-2311

RISKS ASSOCIATED WITH

FASTING IN PATIENTS

WITH DIABETES

During Ramadan

Hypoglycemia

Hyperglycemia

Ketoacidosis

Dehydration & Thrombosis

After Ramadan

Glycemic Control A1C

Body Weight

HYPOGLYCEMIA

The EPIDIAR study

Fasting during Ramadan increased the risk of severe hypoglycemia:

4.7-fold in patients with type 1 diabetes

7.5-fold in patients with type 2 diabetes

Severe hypoglycemia was more frequent in:

1. Patients in whom the dosage and timing of oral hypoglycemic agents or insulin were not adjusted.

2. Patients who reported a significant change in their lifestyle.

Results of the epidemiology of diabetes and Ramadan 1422/2001( EPIDIAR) study. Diabetes care 2004;27:2306-2311

HYPERGLYCEMIA

EPIDIAR study

1. Due to excessive reduction in dosages of medications to prevent hypoglycemia.

2. Increase food/sugar intake.

Results of the epidemiology of diabetes and Ramadan 1422/2001( EPIDIAR) study. Diabetes care 2004;27:2306-2311

5x

3x

DIABETIC KETOACIDOSIS

Pre-Ramadan poorly controlled type 1 diabetic patients, are at

increased risk for development of diabetic ketoacidosis during

fasting.

The risk may be further increased due to excessive reduction of

insulin dosages based on the assumption that food intake is

reduced during Ramadan.

DEHYDRATION& THROMBOSIS

Diabetic patients exhibit a hypercoagulable state due to:

1. Increase in clotting factors.

2. Decrease in endogenous anticoagulants.

3. Impaired fibrinolysis.

Increased blood viscosity secondary to dehydration may enhance

the risk of thrombosis and stroke.

Some medications may cause dehydration e.g SGLT2 .

However, no strong evidence for increased hospitalizations due to

coronary events or stroke during Ramadan.

Safer Fasting

Pre Ramadan Assessment and Education

Self Monitoring

Nutrition

Physical activity

Breaking the Fast

Medication adjustment

PRE-RAMADAN ASSESSMENT

1–2 months before Ramadan.

Medical assessment and engagement in a structured education

program to undertake the fast as safely as possible.

Appropriate blood studies should be ordered and evaluated.

Necessary changes in their diet or medication regimen should be

made.

Assessment should also extend to those who do not wish to fast,

as they are exposed to the risk of hypo- and hyperglycemia during

Ramadan as a reflection of social habits encountered during the

month.

RAMADAN-FOCUSED STRUCTURED

DIABETES EDUCATION

The program should ideally include three components:

* An awareness campaign aimed at people with diabetes, health care professionals, the religious and community leaders as well as the general public.

* Ramadan-focused structured education for health care professionals

* Ramadan- focused structured education for people with diabetes.

HEALTH CARE PROFESSIONALS

EDUCATION

This program also includes:

* The appropriate meal choices to avoid postprandial

hyperglycemia.

* Advice on the timing and intensity of physical activity during

fasting.

* The use of diabetes-related medications and their potential risk

during fasting.

Self Monitoring

Confirm that blood glucose testing does not

constitute breaking fast

Teaching patients who fast how to test their

blood sugar

Encouraging people with diabetes to test their

blood sugar especially if they feel any symptoms

related to hypoglycemia or hyperglycemia

Self Monitoring

At the last two hours prior to breaking the fast.

3 hours following breaking the fast ( after the main

meal )

3 hours after the pre-dawn meal: To monitor the

pre-dawn meal and the treatment given at that

time.

Every 2 - 3 hours during the fast for those on

Insulin and/or SU

Any time the patient feels there is possibility of

hypoglycemia

Nutrition

During Ramadan, the diet should not differ significantly from a

healthy and balanced diet.

In most studies, 50–60% of individuals who fast maintain their body

weight during the month, while 20–25% either gain or lose weight.

Nutrition

Avoid large amounts of foods rich in

carbohydrate and fat, especially at the

sunset meal, because of the delay in

digestion and absorption.

Ingestion of foods containing “complex” carbohydrates may be advisable at the predawn meal, which should be eaten as late as possible before the start of the daily fast.

Fluid intake be increased during non fasting hours.

MA-Pi 2 Diet

Exercise

Normal physical activity may be

maintained.

Excessive physical activity may lead to

higher risk of hypoglycemia and should

be avoided, particularly during the few

hours before the sunset meal.

Repeated cycles of rising, kneeling,

and bowing during praying (Taraweeh)

should be considered a part of the daily

exercise program.

Breaking the fast

1. Hypoglycemia (blood glucose of <60 mg/dl [3.3

mmol /l]) occurs because their blood glucose

may drop further if they delay treatment.

2. Blood glucose reaches <70 mg/dl (3.9 mmol/l) in

the first few hours after the start of the fast,

especially if insulin, sulfonylurea drugs, or

meglitinide are taken at predawn.

3. Blood glucose exceeds 300 mg/dl (16.7 mmol/l).

MANAGEMENT OF TYPE 1 DIABETES

Fasting at Ramadan carries a very high risk for

type 1 diabetic patients.

This risk is particularly exacerbated in:

1. Poorly controlled patients.

2. Those with limited access to medical care.

3. Hypoglycemic unawareness, unstable glycemic

control, or recurrent hospitalizations.

4. Unwilling or unable to monitor their blood glucose

levels several times daily.

MANAGEMENT OF TYPE 1 DIABETES

Basal-bolus regimen is the preferred protocol of

management: safer, with fewer episodes of hyper-

and hypoglycemia.

A frequently used option is once- or twice-daily

injections of intermediate or long-acting insulin

along with pre meal rapid-acting insulin.

It is unlikely that other regimens, including one

or two injections of intermediate-,long-acting, or

premixed insulin, would provide adequate insulin

therapy.

Antihyperglycemic Therapy inType 2 Diabetes

ADA. 7. Approaches to Glycemic Treatment. Diabetes Care 2015;38(suppl 1):S43. Figure 7.1; adapted with permission from Inzucchi SE, et al. Diabetes Care, 2015;38:140-149

28

METFORMIN

Patients treated with metformin alone may safely fast because the possibility of hypoglycemia is minimal.

The timing of the doses be modified to provide two thirds of the total daily dose with the sunset meal and the other third before the predawn meal.

GLITAZONES

The TZDs are not independently

associated with hypoglycemia, though

they can amplify the hypoglycemic

effects of sulfonylureas, glinides and

insulin.

They are associated with:

1. Weight gain

2. Increased appetite.

They require 2-4 weeks to exert substantial antihyperglycemic effects.

They cannot be quickly substituted for agents associated with hypoglycemia during periods of fasting .

-GLUCOSIDASE INHIBITORS

Modest effect on fasting glucose.

Usually used in combination with other agents.

Associated with frequent mild to moderate gastrointestinal effects

SULFONYLUREAS

Chlorpropamide is contraindicated during Ramadan because of the

possibility of prolonged and unpredictable hypoglycemia.

Glyburide/Glibenclamide may be associated with a higher risk of

hypoglycemia than other second-generation SUs e.g. gliclazide,

glimepiride and glipizide.

May NOT be used as a first choice during Ramadan

Because of their worldwide use and relatively low cost, these agents if used

in Ramadan, extreme caution should be enfoced .

Grimaldi A. GUIDE study.Eur J Clin Invet 2004;34:535-542

RendellM.The role of sulfonylureas in the management of type 2 diabetesmellitus. Drugs 2004;64:1339-1358

SHORT-ACTING INSULIN

SECRETAGOGUES

They are better than regular SUs because of their short duration of action.

They may be taken twice daily before the sunset and predawn meals.

However , these drugs may not be the first choice during Ramadan

INCRETIN-BASED THERAY Exenatide can be dosed before meals to minimize appetite &

promote weight loss, it is not associated with a substantial effect

on fasting glucose.

Liraglutide is dosed once a day, independent of meals, and is

more effective in controlling FBG.

Both require titration to effective doses over a period of 2–4 weeks

DPP-4 inhibitors are among the good tolerated drugs for the

treatment of diabetes in Ramadan.

Moderately less effective in A1C lowering than GLP-1

They do not require titration.

Saxagliptin Sitagliptin Linagliptin

Usage and

Indications

• Use with diet and exercise to improve glycemic control in T2DM

• Combination with SFU, MET, TZD

• Combination with insulin

Dosage

Administration

• Once daily, with or

without food

• Tablets:5mg & 2.5mg

(CrCI <50)

• Once daily, with or

without food

• Tablets:100mg, 50mg

(CrCI <50), & 25mg

(CrCI <30)

• Once daily, with or

without food

• Tablets:5mg

• No does adjustment

needed for renal

function

Contraindications • None • Hypersensitivity (i.e.,

anaphylaxis or

angioedema)

• Hypersensitivity (i.e.,

urticaria, angioedema,

or bronchial

hyperreactivity)

Warnings and

Precautions

• When used with a SFU or insulin, a lower dose may be needed to

reduce the risk of hypoglycemia

• Post-marketing reports of pancreatitis (D/C if suspect pancreatitis; Use

with caution in patients with h/o pancreatitis)

FDA Approved DPP-4

Inhibitors

Trajenta® (linagliptin) tablets, Prescribing Information, 2012

Onglyza® (saxagliptin) tablets, Prescribing Information, 2011

Januvia® (sitagliptin) tablets, Prescribing Information, 2012

Exenatide BID Liraglutide Exenatide ER

Usage and

Indications

• Use with diet and exercise to improve glycemic control in T2DM

• Combination with SFUs, MET, TZD

• Exenatide BID and liraglutide: Combination with insulin

Dosage

Administration

• Twice daily before

morning and evening

meals

• 5-10 mcg SC BID

• Once daily at any time

of day (independent of

meals)

• 1.2-1.8 mg SC Q day

• Once weekly

• 2 mg SC Q week

Contraindications • Hypersensitivity to

exenatide or any

product components

• Personal of family

history of medullary

thyroid ca. or MEN2

• Personal of family

history of medullary

thyroid ca. or MEN2

Warnings and

Precautions

• Post-marketing reports of pancreatitis (D/C if suspect pancreatitis;

Consider other therapies in patients with h/o pancreatitis)

• Medullary thyroid cancer (liraglutide and exenatide extended-release)

• Do not use in patients with severe renal impairment or ESRD

• Not recommended for patients with gastroparesis

• Consider reducing does of insulin when used in combination to reduce

risk of hypoglycemia

FDA Approved

GLP-1 Receptor Agonists

Bydureon® (exenatide extended-release for injectable suspension), Prescribing Information, 2012

Victoza® (liraglutide [rDNA origin] injection), Prescribing Information, 2012

Byetta® (exenatide) injection, Prescribing Information, 2011

SGLT2 Inhibitors

(canagliflozin, dapagliflozin)

Physicians’ desk reference (68th ed.). (2014). Montvale, NJ: Physicians’ Desk Reference.

Mechanism

of Action

Reduce renal glucose reabsorption and increases urinary glucose excretion (mechanism of

action is independent of insulin)

Benefits No hypoglycemia

Mean A1C reduction approximately 1% (starting from a baseline A1c of ~8.0%)

Weight loss (2-5%) and systolic BP reduction (2-6mmHg)

Concerns Genital mycotic infections

Hypotension secondary to volume contracture especially in the elderly using loop diuretics

Dehydration especially in hot seasons without adequate fluid intake

Assess renal function before initiating and during therap. Do not initiate if e-GFR

is below 45 mL/min (cana-) or <60 mL/min (dapa-)

Increased LDL-C

Bladder cancer: Dapagliflozin should not be used in pts with active bladder cancer and

used with caution in pts with h/o bladder cancer.

Dosing Canagliflozin (INVOKANA®

)

Starting dose: 100 mg daily before first meal of

day

Increase to 300 mg daily if tolerating 100 mg daily

and eGFR > 60 mL/min

Dapagliflozin (FARXIGA®

)

Starting dose: 5mg daily in morning with or

without food

Increase to 10 mg daily if tolerating and need

additional glycemic control

Recent FDA warning !

Posted on May 15th 2015 FDA is warning that the type 2 diabetes medicines canagliflozin, dapagliflozin,

and empagliflozin may lead to ketoacidosis

Health care professionals should evaluate for the presence of acidosis,

including ketoacidosis, in patients experiencing these signs or symptoms

http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedic

alProducts/ucm446994.htm

INSULIN

Problems facing type 2 diabetic patients who administer insulin are similar to those with type 1 diabetes, except that the incidence of hypoglycemia is less.

The aim is to maintain necessary levels of basal insulin to prevent fasting hyperglycemia.

Effective strategy: use of intermediate- or long acting insulin preparations plus a short acting insulin administered before meals.

Hypoglycemia remains a risk, especially in patients:

1. Who have required insulin therapy for a number of years.

2. Where insulin deficiency predominates in the pathophysiology.

Very elderly patients with type 2 diabetes may be at especially high risk.

INSULIN

One injection of a long-acting or intermediate-acting insulin can

provide adequate coverage in some patients as long as the dosage

is appropriately individualized.

Most patients will require rapid- or short-acting insulin in

combination with the basal insulin at meals, particularly at the

evening meal, which typically contains a larger caloric load.

Evidence suggests that the use of a rapid acting insulin analog

instead of regular human insulin before meals in patients with

type 2 diabetes who fast during Ramadan is associated with less

hypoglycemia and smaller postprandial glucose excursions.

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Before Ramadan treatment During Ramadan treatment

Patients on diet and exercise control Consider modifying the time and intensity of

physical activity and ensure adequate fluid

intake

Patients on oral hypoglycemic agents Ensure adequate fluid intake

Biguanide, metforming 500 mg 3x daily Metformin, 1000 mg at the sunset meal

Metformin, 500 mg at the predawn meal

TZDs, AGIs , incretin-based therapies or

SGLT2

No change needed

Sulfonylurea 1x daily Dose should be given before the sunset meal

Adjust dose based on glycemic control and

risk of hypoglycemia

Sulfonylurea 2x daily Half the usual morning does at the predawn

meal

Usual dose at the sunset meal

Patients on insulin Ensure adequate fluid intake

Premixed or intermediates acting insulin 2x

daily

Consider changing to long-acting or

intermediate insulin in the evening and short

or rapid-acting insulin with meals

Take usual dose at sunset meal

Half usual dose at predawn meal

PREGNANCY AND FASTING

Elevated blood glucose and A1C levels in pregnancy are associated with increased risk for major congenital malformations.

Fasting during pregnancy would be expected to carry a high risk of morbidity and mortality to the fetus and mother, although controversy exists.

While pregnant Muslim women are exempted from fasting during

Ramadan, some with known diabetes (type 1, type 2, or

gestational) insist on fasting during Ramadan.

They constitute a high-risk group, and their management requires

intensive care.

Women with pre gestational or gestational diabetes should be

strongly advised to not fast during Ramadan.

Thank you