Management of diabetes in

advanced CKD

Dr Ionut Nistor
Asistent Universitar UMF Iasi
Medic specialist nefrologie
 Treatment of DM with eGFR < 45
ml/min/1.73m or dialysis
Glucose regulation
HbA1c cut-off levels
Oral medication or insulin?
 Glycemic control vs survival
HbA1c cut-off levels

prospective observational study; mean FU 2.7 yrs

150 ESRD with DM, 60.510.2 yrs
BL HbA1c <7.5% 7.5%
n= 93 57
1-yr survival (%) 84.9 70.2
3-yr 57.8 43.7
5-yr 31.7 12.1
Morioka, Diab Care 2001; 24: 909
Mortality rate in ESRD and DM: HbA1c
ACCORD, ADVANCE, UKPDS, VADT
The Cochrane Library 2011, Issue 6
The Cochrane Library 2011, Issue 6
 Recommendations
Authors: Henk Bilo and Laurens Weekers

We recommend against tightening glycaemic control if this results in or increases

the risk for severe hypoglycemic episodes (1A)

We recommend interventions to tighten glycaemic control with the intention to

lower HbA1C when values are >8.5% (1C)

We suggest cautious interventions to tighten glycaemic control with the intention

to lower HbA1C when HbA1C values are >7% but <8.5% only when the projected
benefits (microvascular complications, retinopathy) clearly outweigh the risk for
hypoglycaemia, taking into account general condition of the patient (2D)

We recommend intense self monitoring in patients at risk for hypoglycaemia (2D)

 Treatment of DM with eGFR < 45
ml/min/1.73m or dialysis
Glucose regulation
HbA1c cut-off levels
Oral medication or insulin?
Adjustments with progressively lower GFR!
 Facts and myths in DM and CKD

metformin often induces life threatening acidosis

when administered in CKD patients
 Cochrane metformin 2010
Pooled data from 347 comparative trials and cohort
studies revealed no cases of fatal or nonfatal lactic
acidosis in 70,490 patient-years of metformin use or in
55,451 patients-years in the non-metformin group.
There is no evidence from prospective comparative
trials or from observational cohort studies that
metformin is associated with an increased risk of lactic
acidosis, or with increased levels of lactate, compared
to other anti-hyperglycemic treatments.
 Facts and myths in DM and CKD

Herrington WG, Levy JB. Metformin: effective and safe in renal disease. Int Urol Nephrol
2008; 40: 411-417
 Facts and myths in DM and CKD

oral medication should be stopped when an eGFR

of < 30 ml/min/1.73m is reached
No differences between gliclazide 80 mg and gliclazide MR 30 mg
 Comparing medication
Glucose- Effectiveness hypoglycaemias Long term Use in Costs
lowering on HbA1c safety CKD

insulin +++ ++ + + high

SU / 1-1.5% + + -/+ low
meglitinides
Glucose-
normalising
metformin 1-1.5% + -/? low
TZDs 1-1.5% - + intermediate
DPP-IV I < 1% ? + high
Incretin 1-2% ? -/+ high
analogues
Title: IIQ5: In patients with renal failure (eGFR < 45mL/min/1.73m), is
maximal oral therapy better than starting/adding insulin in an earlier
stage?
Title: IIQ6: Is any oral drug superior to another in terms of
mortality/complications/glycemic control in diabetic patients with renal
failure (eGFR <45 mL/min/1.73m) or on dialysis?

Recommendations
* We recommend metformin in a dose adapted to renal function as a first line agent
when lifestyle measures alone are insufficient to get HbA1C in the desired range (1B)

* There is insufficient evidence to support insulin over an additional oral agent as add on
second line treatment

* we recommend instructing patients to withhold metformin[W1] in[W2] conditions of

pending dehydration, when undergoing contrast media investigations, or when there is a
risk for AKI

advice for clinical practice

Consider production of credit-card type flyers with instructions for patients on when to
temporarily withdraw methformin
[W1]a patient oriented decision and informtion aid will be highly needed!!!!
[W2]consider asking EMA to reconsider the official medication insert
http://www.european-renal-best-practice.org/content/erbp-official-
documents
NDT Perspectives: Paul Arnouts, Davide Bolignano, Ionut Nistor, Henk Bilo, Luigi Gnudi, James Heaf, and
Wim van Biesen. Glucose-lowering drugs in patients with chronic kidney disease: a narrative review on
pharmacokinetic properties Nephrol. Dial. Transplant. first published online December 8, 2013
doi:10.1093/ndt/gft462
CKD Challenge: dose recommendations
Multumesc!