Hypoglycemia Among Type 2 Diabetics Fasting Ramadan Dr. Khaled Tayeb tayebkhaled@hotmail

2. Hypoglycemia Among Type 2 Diabetics Fasting RamadanDr. Khaled Tayebtayebkhaled@hotmail.com

3. 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 (183) يَا أَيُّهَا الَّذِينَ آمَنُواْ كُتِبَ عَلَيْكُمُ الصِّيَامُ كَمَا كُتِبَ عَلَى الَّذِينَ مِن قَبْلِكُمْ لَعَلَّكُمْ تَتَّقُونَ (184) أَيَّامًا مَّعْدُودَاتٍ فَمَن كَانَ مِنكُم مَّرِيضًا أَوْ عَلَى سَفَرٍ فَعِدَّةٌ مِّنْ أَيَّامٍ أُخَرَ وَعَلَى الَّذِينَ يُطِيقُونَهُ فِدْيَةٌ طَعَامُ مِسْكِينٍ فَمَن تَطَوَّعَ خَيْرًا فَهُوَ خَيْرٌ لَّهُ وَأَن تَصُومُواْ خَيْرٌ لَّكُمْ إِن كُنتُمْ تَعْلَمُونَ (185) شَهْرُ رَمَضَانَ الَّذِيَ أُنزِلَ فِيهِ الْقُرْآنُ هُدًى لِّلنَّاسِ وَبَيِّنَاتٍ مِّنَ الْهُدَى وَالْفُرْقَانِ فَمَن شَهِدَ مِنكُمُ الشَّهْرَ فَلْيَصُمْهُ وَمَن كَانَ مَرِيضًا أَوْ عَلَى سَفَرٍ فَعِدَّةٌ مِّنْ أَيَّامٍ أُخَرَ يُرِيدُ اللّهُ بِكُمُ الْيُسْرَ وَلاَ يُرِيدُ بِكُمُ الْعُسْرَ وَلِتُكْمِلُواْ الْعِدَّةَ وَلِتُكَبِّرُواْ اللّهَ عَلَى مَا هَدَاكُمْ وَلَعَلَّكُمْ تَشْكُرُونَ

4. Recommendations for Management of Diabetes During Ramadan Diabetes Care Volume 33, Number 8, August 2010

5. Major risk associated with fasting in patients with diabetes • Hypoglycemia • Hyperglycemia • Diabetic ketoacidosis • Dehydration and thrombosis Recommendations for Diabetic Individuals during Ramadan, Diabetes Care , vol 33, num. 8, August2010

6. Hypoglycaemia • 2 – 4% of mortality in patients with type 1 diabetes. • Rates of hypoglycaemia are some several-fold lower in patients with type 2 compared with type 1 diabetes • Rates being lower in patients with type 2 diabetes treated with oral agents. Recommendations for Diabetic Individuals during Ramadan, Diabetes Care , vol 33, num. 8, August2010

7. Categories of risks in patients with type 1 or type 2 diabetes who fast during Ramadan 1. Very high risk • Severe hypoglycaemia within the last 3 months prior to Ramadan. • A history of recurrent hypoglycaemia. • Hypoglycaemia unawareness. • Sustained poor glycemic control. • Ketoacidosis within the last 3 months prior to Ramadan. Recommendations for Diabetic Individuals during Ramadan, Diabetes Care , vol 33, num. 8, August2010

8. Breaking the Fast All patients must always and immediately end their fast if: • Hypoglycaemia (blood glucose of <60mg/dl). • Blood glucose reaches <70 mg in the first few hours after the start of the fast, especially if insulin, sulfonylurea drugs, or neglitinide are taken at predawn. • Blood glucose exceeds 300 mg with symptoms of hyperglycaemia. Recommendations for Diabetic Individuals during Ramadan, Diabetes Care , vol 33, num. 8, August2010

9. (4.7 fold) (7.5 fold)

10. Change in outcome measures during Ramadan in participants receiving both gliclazide and metformin1 Hypoglycaemia in study control group on Metfromin + Gliclazide Ramadan 2008 Int J Clin Pract 2009; 63: 1446–50 10

11. Hypoglycemia in Sulphonylurea-Treated Subjects with Type 2 Diabetes Undergoing Ramadan Fasting:A Five-Country Observational Study Current Medical Research & Opinion Vol. 27, No. 6, 2011, 1237-1242

12. Objectives • To determine the incidence of hypoglycemia during Ramadan in Muslim subjects with type 2 diabetes treated with a sulphonylurea. Current Medical Research & Opinion Vol. 27, No. 6, 2011, 1237-1242

13. Subjects & Methods • Eligible subjects • Muslim patients with type 2 diabetes treated with Sulphonylureas( Glimiperide, Glyclazide , or Glibenclamide) • With or without Metformin • Age ≥ 18 years old • Excluded subjects • Patients with Type 1 diabetes • Patients with Insulin treated type 2 diabetes Current Medical Research & Opinion Vol. 27, No. 6, 2011, 1237-1242

14. Subjects & Methods • Subjects were recruited from 5 countries. • 300 subjects were selected per country. • Diabetes Center in Holy Makkah and other centers from (UAE, India, Malaysia, and occupied Palestine ). Current Medical Research & Opinion Vol. 27, No. 6, 2011, 1237-1242

15. Subjects & Methods Patients were given a daily dairy card to record .. • any hypoglycemic symptoms and complications • The time from the start of hypoglycemic symptoms and the last meal and medications • Self monitor blood glucose • Need for assistance to treat hypos. • The fasting was broken or not. • Cards to be filled daily regardless of symptoms Current Medical Research & Opinion Vol. 27, No. 6, 2011, 1237-1242

16. Subjects & Methods • The hypoglycemic events were further classified into.. - Symptomatic : (headache, sweating, tremors, palpitation, etc..) - Documented: symptomatic with BG ≤ 70 mg/dl. - Severe: requiring medical or non- medical assistance. Current Medical Research & Opinion Vol. 27, No. 6, 2011, 1237-1242

17. Patients Characteristic in the Study Current Medical Research & Opinion Vol. 27, No. 6, 2011, 1237-1242

18. Sulponylurea use by country in the study Current Medical Research & Opinion Vol. 27, No. 6, 2011, 1237-1242

19. Results • The daily dairy card were returned by 1378 patients from total 1397 patients. • Symptomatic hypoglycemia was 40% in occupied Palestine and 10% in Saudi Arabia • Over all symptomatic hypoglycemic events were recorded in 271 subjects (19.7%) • Headache represent 14.5%, sweating 10.2%, tremors 8.5% and palpitation 7%. Current Medical Research & Opinion Vol. 27, No. 6, 2011, 1237-1242

20. Incidence of symptomatic hypoglycemia during Ramadan by countries Current Medical Research & Opinion Vol. 27, No. 6, 2011, 1237-1242

21. Incidence of hypoglycemia during Ramadan by type Current Medical Research & Opinion Vol. 27, No. 6, 2011, 1237-1242

22. Incidence of hypoglycemia during Ramadan by type 86% 6.7% 3.7% 3.6% Severe hypoglycemic events requiring medical assistance Symptomatic hypoglycemic events Documented hypoglycemic events Severe hypoglycemic events Type of hypoglycemia

23. Incidence of hypoglycemia during Ramadan by types of drug Current Medical Research & Opinion Vol. 27, No. 6, 2011, 1237-1242

24. Results Symptomatic hypoglycemia events 1095 Documented hypoglycemic events were similar across all sulphonylurea groups 3.6%, . Events not requiring medical assistance 3.7% Events requiring assistance 6.7% . Subjects experienced a serious complication 1.2% . Current Medical Research & Opinion Vol. 27, No. 6, 2011, 1237-1242

25. Discussion • The incidence of severe hypoglycemia requiring medical or non medical assistance or hospitalization were less than other studies. • In the EPIDAR study, 2% of patients hospitalized in comparison to 0.5% in this study. (Diabetes Care 2004; 2306-11) • Health care resources utilization, was less in this study. The less severe hypoglycemia events or better education regarding the symptoms could explain this. Current Medical Research & Opinion Vol. 27, No. 6, 2011, 1237-1242

26. The incidence of Hypoglycaemia in Muslim Type 2 Diabetics treated with Sitagliptin or a Sulphoylurea during Ramadan. Aim To compare the incidence of symptomatic hypoglycaemia with Sitagliptin or A Sulphonylurea during Ramadan. Current Medical Research & Opinion Vol. 27, No. 6, 2011, 1237-1242

27. Patients and study design A prospective, open-label, randomised study. 6 countries, 43 clinical sites. 1243 patients of whom 1066 randomized to treatment. Muslim Type 2 diabetics willing to fast Ramadan. Age : > 18 Yrs. Treated with a sulphonylurea for at least 3 months before study with or without metformin and had HbA1c < 10%. Current Medical Research & Opinion Vol. 27, No. 6, 2011, 1237-1242

28. Pre-Randomization Treatment Current Medical Research & Opinion Vol. 27, No. 6, 2011, 1237-1242

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

30. Results *n/N (%) Sitagliptin *n/N (%) Sulphonylurea 22.1% 21.2% 20.0% 20.0% 18.6% 11.9% 10.3% 9.9% 7.1% 6.7% 5.1% 0% 0.5% 0.5% Overall Egypt Palestien Jordan Lebanon Saudi Arabia UAE *no of patients experiencing event /N overall or in each country by treatment. (%) Current Medical Research & Opinion Vol. 27, No. 6, 2011, 1237-1242

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

32. Severe hypoglycemia Mild hypoglycemia Fear of hypoglycemiais a major concern for patients 1. Pramming S et al. Diabet Med 1991;8:217–222 Male Female Male Female Blindness Kidney problems Male Female Blindness Male Female Very worried Not worried

34. Hypoglycaemic Events X4 increase

35. 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: Aim and objectives VECTOR - 2011

36. VECTOR: Results - Hypoglycaemic events (HE) VECTOR - 2011 Mean between-group difference in patients who experienced at least one HE was –41·7% (p = 0·0002)

37. VECTOR: HbA1c VECTOR - 2011 The between group difference was −0·6% (p = 0·0262) (7·7% to 7·2%) (7·2% vs 7·3%)

38. VECTOR :Adherence Only 1 patient in the Vildagliptin group missed at least one dose, compared with 10 patients in the SU group. p = 0·0204

39. * 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)

40. 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.

42. 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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