Talk on MANAGEMENT OF DIABETES IN CHRONIC KIDNEY DISEASE (Special reference to Use of Metformin In CKD). Presented on 25th June 2017 at THE METFORMIN MEET in Vadodara, India

1. MANAGEMENT OF DIABETES IN
PATIENT WITH CKD
with Special Reference to
Metformin use in CKD
DR. OM J LAKHANI
MD, DNB (ENDOCRINOLOGY)
CONSULTANT ENDOCRINOLOGIST
ZYDUS HOSPITALS, AHMEDABAD

2. Outline of the Talk
1. Challenges to Management of Diabetes
in CKD
2. Goals of therapy in Diabetes and CKD
3. Monitoring of Glycemic control in CKD
4. Use of Metformin in CKD
5. Overview of Use of other OAD in CKD
6. Insulin use in CKD
7. Take home messages

3. Challenges to Management of
Diabetes in CKD
1. HbA1c may be unreliable because of uremia
2. Dextrose in peritoneal fluid can interfere
with diabetes management
3. Metabolism of oral drugs is disturbed in CKD
patients
4. Changes in dietary intake and exercise is
typical in CKD
5. Changes in Insulin resistance and metabolism
of Insulin

4. GOALS OF THERAPY

5. Target for CKD (Not on Dialysis)
• The target remain same of 7% as for
non CKD patients
• However, patients who are at high
risk of hypoglycemia or limited life
expectancy may have more liberal
targets

6. Target for CKD for those on Dialysis
• Young patients <50 years without
comorbidities- close to 7%
• Older patients and/or having
comorbidities and high risk of
hypoglycemia- close to 8%

7. METFORMIN IN CKD

8. • GFR >45 can be used* (Some
exceptions)
• GFR 30-45- Maximum Metformin
use of 1000 mg /day
• GFR < 30 – Avoid metformin
Metformin in CKD (Current
Guidelines)

9. Also avoid in patients with GFR <60 with
high risk of lactic acidosis like
• Hypotension
• Shock
• Hypoxia
• Radiocontrast use
• Sepsis

10. Major concern with Metformin
• The use of Metformin in CKD is
associated with increase risk of
Lactic acidosis

11. METFORMIN AND LACTIC ACIDOSIS –
AN OLD WITCH’S TALE

12. • Q. In real life scenario in which
cases would metformin lead to
lactic acidosis in context of renal
dysfunction ?

13. 1. Acute Uremia
2. Failure to reduce dose of
Metformin in established CKD

14. 1. Metformin overdose
2. MIDD- maternally inherited diabetes and
deafness
3. Metformin use in renal failure
4. Liver failure
5. Heart failure
6. Dehydration
7. Sepsis and shock
8. Hypovoluemia

15. Vicious circle
Acute
uremia +
Metformin
Lactic
acidosis
Diarrhea
and
vomiting
Pre-renal
AKI

16. • Phenformin is 140 times more
lactogenic effect compared to
metformin

17. • Q. What are the Clinical features of
lactic acidosis ?

18. • Non specific
• Nausea, vomiting , abdominal pain
etc

19. Q. What is type A and type B lactic
acidosis ?

20. • Type A- due to hypoperfusion
• Type B – not due to hypoperfusion,
due to toxins or other causes

21. • Q. Is it true that diabetics per se
have increased risk of lactic acidosis
?

22. • Yes
• Diabetes itself predisposes to Lactic
acidosis
• The concentration of lactate in
diabetics is twice that of healthy
controls

23. • Q. Is there any Epidemiological
evidence of metformin causing
lactic acidosis ?

24. • No
• In a Cochrane analysis of 347
studies involving more than 70,000
patient years of Metformin use
revealed NO CASES of Metformin
induced lactic acidosis

25. • On the other hand a population
based study in diabetics NOT on
Metformin therapy had incidence
of Lactic acidosis of around 10 per
100,000 patient years

26. • Q. Can Metformin be used with
Contrast used in Radiology ?

28. • GFR - <45 ml/min/1.73 m2
• Stop Metformin for 48 hrs before IV
contrast
• Reassess Renal function 48 hrs
after stopping contrast
• If no attrition of Renal function-
restart Metformin

29. • Q. What about Gadolinium used in
MRI ?

30. • CIN due to Gadolinium is rare
• No special precautions are needed
when patients receiving metformin
are given gadolinium-based
contrast agents

31. USE OF OTHER ORAL
ANTIDIABETICS IN CKD

32. • National Kidney Foundation Kidney
Disease Outcomes Quality Initiative
(NKF KDOQI)™ has provided
evidence-based clinical practice
guidelines

36. • Q. What is the dose of Sitagliptin in
patients with renal failure ?

37. • eGFR- 30-50  50 mg
• <30  25 mg

38. • Q. Can alpha galactosidase
inhibitors recommended in CKD ? If
no they Why not ?

39. • Alpha Glucosidase inhibitors are
avoided in patient with eGFR <30
• They have active metabolites
absorbed which have renal
excretion

40. • Q. What is the recommendation of
SGLT2i with GFR ?

41. • GFR <30- contraindicated
• GFR 45-60- not recommended
• So basically GFR < 60- avoid

42. • Q. What about use of Pioglitazone
in CKD ?

43. • Pioglitazone can be used in CKD
without dose adjustment
• However there is an increased risk
of fluid retention with use of
Pioglitazone

44. • Q. What about use of GLP1
analogue (Liraglutide) in CKD ?

45. • No dosage adjustment necessary;
• It must be used with caution when
initiating therapy and with dose
escalation
• There is limited data in patients with
severe renal impairment.
• Acute renal failure and exacerbation of
chronic renal failure have been
reported.

46. INSULIN USE IN CKD

47. • Q. What are changes in Insulin
physiology in CKD ?

48. 1. Increased insulin resistance
2. Reduced hepatic insulin
metabolism
3. Reduced clearance of insulin from
circulation
4. Reduced insulin synthesis

49. • Q. What is the end clinical effect on
Insulin dosage in CKD ?

50. • CKD may lead to both increase or
reduced insulin requirement

55. • Q. What is the adjustment of insulin
dose recommended in patients
with CKD ?

56. • GFR >50 – no dose requirement
• GFR 10-50- 25% reduction in dose
• GFR <10 % - 50% reduction in dose of
insulin

57. • Q. Is there a risk of spontaneous
hypoglycemia in CKD ?

58. • Yes
• CKD predisposes to spontaneous
hypoglycemia

59. • Q. What is the reason for insulin
resistance seen in CKD ?

60. 1. Increase of PTH
2. Reduce glycogen synthesis  this is
characteristic in CKD  hence there is
increased glucose in circulation which
is not converted to glycogen
3. Increased hepatic gluconeogenesis 
because of reduced glycogen and
reduced renal gluconeogenesis

61. Key point
• In CKD there is reduced hepatic
glycogen synthesis and increased
hepatic gluconeogenesis

62. • Q. What is the reason for reduced
insulin synthesis ?

63. 1. Reduced calcitriol
2. PTH suppresses insulin synthesis
3. Metabolic acidosis suppresses
insulin synthesis

64. • Q. Give some guidance for
management of hyperglycemia in
in-patients during hemodialysis ?

65. 1. Patients have different insulin
sensitivity both pre and post
dialysis
2. Reduce basal insulin by 25% on day
following dialysis compared to day
before the dialysis

66. CONCLUSION AND TAKE HOME
MESSAGES

67. Goals of therapy
• CKD (Not on dialysis) – < 7%
• CKD (on Dialysis)
–Young without Comorbidities – close
to 7%
–Old with Comorbidities – close to 8%

68. • GFR >45 can be used* (Some
exceptions)
• GFR 30-45- Maximum Metformin
use of 1000 mg /day
• GFR < 30 – Avoid metformin
Metformin in CKD

69. Metformin and Constrast
• If GFR <45 – Stop Metformin 48 hrs
before and 48 hrs after contrast

70. Other Drugs in CKD (Non dialysis)
• Gliptin – Linaglitpin needs no dose
adjustment , other need dose
adjustment
• SGLT2i – Avoid if GFR <60
• Alpha glucosidase- Avoid if eGFR <30
• Pioglitazone – Can use with caution
• GLP1 analogue- Can be used (?
Caution)

71. Patients on Dialysis
• Prefer Insulin with dose
adjustments
• Reduce basal insulin dose by 25% on
day of dialysis

72. CKD and Insulin
• CKD may lead to both increase or
reduced insulin requirement

73. Thank You !