Supplement to Journal of The Association of Physicians of India ■ Published on 1st of Every Month 1st October, 2016 27

Consensus Statement on Dose Modifications

of Anti Diabetic Agents used in Patients with
Diabetes and Chronic Kidney Disease
Binayak Sinha1, KK Gangopadhyay2, DC Sharma3, Arthur Asirvatham4, Parminder Singh5

which may guide clinicians in

Abstract managing Hyperglycemia in patients
CKD with outcomes in mind.
Patients with Diabetes and declining renal function pose complex challenges to
the clinician, including the management of comorbidities such as hypertension, Methods
hyperlipidemias, cardiovascular (CV) disease, anemia, and abnormal bone
metabolism. The prevalence of stage 3 or worse chronic kidney disease (CKD) in The Consensus group evaluated
patients with T2DM is increasing. Diabetes is a leading cause of end-stage renal existing evidence including current
disease (ESRD) and dialysis. guidelines, published trials and the
prescribing information of various
The aim of the consensus group was to focus on the challenges with glycemic Anti Diabetic agents with respect
management, with particular emphasis to safe use of anti-diabetic agents across to management of Hyperglycaemia
stages of renal dysfunction. in CKD. Existing Guidelines
Published Literature, product information and major clinical guidelines from USA KDOQI recommendations 2012
and India were reviewed and summarized. These drugs included metformin, the was found to be relevant to the
discussion compared to KDIGO. The
second- or third-generation sulfonylureas (SUs), alpha-glucosidase inhibitors
members then discussed and laid
(AGIs), thiazolidinediones (TZDs), dipeptidyl peptidase-4 (DPP-4) inhibitors,
down recommendations related to
sodium–glucose co-transporter 2 (SGLT2) inhibitors, glucagon-like peptide-1 Glycaemic control in patients with
(GLP-1) receptor agonists, and currently available insulins. CKD and specific recommendations
Consensus Recommendations for Glycemic targets and dose modifications of related to dose modification of each
all Anti Diabetic agents are summarized. class of Anti Diabetic agents.
Glomerular filtration rate is the
best measure of overall kidney
function in health and disease. 15
Introduction many therapeutic challenges,
The normal level of GFR varies
including the management of
Type 2 diabetes mellitus (T2DM) comorbidities such as hypertension, according to age, sex, and body
is by far the most common form hyperlipidaemia, cardiovascular size. Normal GFR in young adults
of diabetes, comprising 90% of all (CV) disease, anemia, and abnormal is approximately 120 to 130 ml/
diabetes cases and is therefore a bone and mineral metabolism. 4 min/1.73m2 and declines with
major health issue. The prevalence There is a dearth of evidence and age. A GFR level less than 60 ml/
of stage 3 or worse chronic kidney recommendations from International min/1.73m 2 represents loss of half
disease (CKD) in patients with and National organizations/bodies or more of the adult level of normal
T2DM is generally reported to be regarding glycaemic management kidney function. Below this level,
between 21% and 38%. 1-8, 12,13 in patients with CKD. Regulatory the prevalence of complications of
bodies across the globe propose chronic kidney disease increases. 16-
Diabetes is a leading cause of 18
Decreased kidney function is
end-stage renal disease (ESRD) and differing statements with respect to
dose modifications of anti-diabetic practically assessed by estimating
dialysis; 40% of patients in France the GFR (eGFR) using either
and 45% in the United States (US) agents. The aim of this consensus
was to evaluate existing evidence Cockcroft–Gault or Modification of
had diabetes at initiation of dialysis. Diet in Renal Disease (MDRD) study
In Canada, 35% of patients who relevant to glycaemic management
of T2DM in the setting of CKD and equations. 19, 20, 22
initiated treatment for ESRD in
2010 had diabetes. Diabetes is also propose a set of recommendations The stages of CKD which will
associated with one of the lowest
5-year survival rates in patients 1
Department of Endocrinology, AMRI Hospital, Kolkata, West Bengal; 2Consultant Endocrinologist, Fortis
receiving dialysis. 9,10,14
Hospital, Kolkata, West Bengal; 3Senior Consultant, Dr. DC Sharma Institute of Diabetes, Thyroid and Hormones-
Pa t i e n t s w i t h d i a b e t e s a n d Srajan Hospital Pvt. Ltd., Udaipur, Rajasthan; 4Arthur Asirvatham Hospital, Madurai, Tamil Nadu; 5Division of
declining kidney function present Endocrinology, Dayanand Medical College and Hospital, Ludhiana, Punjab
28 Supplement to Journal of The Association of Physicians of India ■ Published on 1st of Every Month 1st October, 2016
Table 1: Stages of CKD
Stage Description
1 Kidney damage* with normal or increased GFR
2 Kidney damage* with mildly decreased GFR
3 Moderately decreased GFR
4 Severely decreased GFR 15–29
5 Kidney failure
*Kidney damage is defined as abnormalities on pathological, urine, blood, or imaging tests.
Adapted. National Kidney Foundation (2012) KDOQI Clinical Practice Guidelines for Diabetes
and CKD: 2012 update. Am J Kidney Dis 60:850–886
feature in further discussions will
be as proposed by the NKF-KDOQI
(Table 1). Defining the stage of
chronic kidney disease is the key first
step in developing the appropriate
clinical action plan. 19
Consensus
Recommendation 1:
Glycemic Targets
The ADA, the EASD, and
the IDF recommend a glycated
hemoglobin (HbA1c) target of <7%
for most patients with diabetes.
Customization of this general target
is based on patient characteristics,
with tighter control.
1.1 We r e c o m m e n d a t a r g e t
hemoglobin A1c (HbA1c)
of ~7.0% to prevent or
delay progression of the
microvascular complications
of diabetes, including DKD.
1.2 We recommend not treating
to an HbA1c target of
<7.0% in patients at risk of
hypoglycemia.
1.3 We s u g g e s t t h a t t a r g e t
HbA1c be extended above
7.0% in individuals with
co-morbidities or limited
life expectancy and risk of
hypoglycemia.
1.1 We r e c o m m e n d a t a r g e t
hemoglobin A1c (HbA1c)
of ~7.0% to prevent or
delay progression of the
microvascular complications
of diabetes, including DKD.
Few long-term observational
cohort studies and secondary
or post hoc analyses of
interventional studies using
ACE-Is or ARBs found that
poorer glycemic control was
associated with a greater rate
risk of the primary endpoints,
GFR (mL/min/1.73 m2)
defined by composites of
≥90
major adverse cardiovascular
disease (CVD) events, in any
60-89
of these studies.
30-59
15-29 Moreover, there was an
<15 or dialysis increase in all-cause mortality
among the intensively-treated
group compared to the
conventionally-treated group
in the ACCORD study. 27,29,30
of fall of GFR in patients with
type 1 diabetes. 21-25
The reasons for this finding
are uncertain, although
The EDIC/DCCT follow up
further analysis showed
study recently reported that
that increased mortality was
2.0% (1.6/1000 person-years) of
not directly attributable to
participants in the previously
hypoglycemia. 31 Therefore,
intensive treatment group and
5.5% (3.0/1000 personyears)
l o we r i n g H b A 1 c t o l e ve l s
7.0% is not recommended in
of those in the previously
patients with diabetes who
conventional treatment group
are at risk for hypoglycemia,
developed sustained estimated
including those treated with
glomerular filtration rate
insulin or sulfonylureas and/
(eGFR) measurements 60 ml/
or have advanced CKD.
min/1.73 m 2 with a relative
risk (RR) reduction of 50% (p< 1.3 We s u g g e s t t h a t t a r g e t
0.006). 26 HbA1c be extended above
7.0% in individuals with
For patients with type 2
co-morbidities or limited
diabetes, intensive treatment
life expectancy and risk of
in the UKPDS was associated
hypoglycemia.
with a 67% risk reduction
for a doubling of plasma Years of intensive glycemic
creatinine levels at 9 years control (HbA1c 7%) are
(0.71% of the intensive group required before a reduction
and 1.76% of the conventional in the incidence of
group, p<0.027).15 None of complications, such as kidney
failure or blindness, becomes
the three more recent studies
mentioned above (ADVANCE, evident. 32,33 . In individuals
70-79 years of age who are
A C C O R D , VA D T ) s h o we d
significant benefits of more taking insulin, the risk of
intensive glycemic control on hypoglycaemia begins to
creatinine-based estimates of increase with HbA1c 7%. 34
GFR. 27-29 Moreover, in patients with
type 2 diabetes, one study
1.2 We recommend not treating
to an HbA1c target of showed that the presence of co-
morbidities abrogates benefits
<7.0% in patients at risk of
hypoglycemia. of lower HbA1c levels on CVD
events. 35 Therefore, a target
The three most recent clinical
HbA1c of 7.0% is suggested
trials (ADVANCE, ACCORD,
for patients with diabetes who
a n d VA D T ) a l l s h o w e d
are at risk of hypoglycemia
substantial increases (range
and have clinically-significant
1.5-3 fold) in severe and non-
co-morbidities or limited life
severe hypoglycemia among
expectancy.
patients with type 2 diabetes
w h o we r e r e c e i v i n g m o r e
intensive therapy. Intensifying
glycemic control beyond
conventional management
did not result in decreased
 Supplement to Journal of The Association of Physicians of India ■ Published on 1st of Every Month 1st October, 2016
Table 2: Guidelines and Prescribing information for the use of Sulphonylureas in
CKD
Agent KDOQI 2012
Glipizide No dose adjustment
Glimepiride Start conservatively at 1 mg daily Start conservatively at 1 mg daily
Glyburide Avoid use
Gliclazide No dose adjustment
Table 3: Guidelines and Prescribing information for the use of Thiazolidinediones
in CKD
Agent KDOQI guidelines 2012
eGFR in ml/min/1.72 m2
<90 - >60 <60 - >30
Pioglitazone No dose adjustment
Consensus
Recommendation 2: Oral
Anti Diabetic agents in
CKD
While patients with mild renal
i n s u f f i c i e n c y c a n r e c e i ve m o s t
antihyperglycemic treatments
without concern, patients with
stages 3, 4, or 5 CKD often require
treatment adjustments according to
the degree of renal insufficiency.
These adjustments include lowering
the dose or discontinuing a drug
altogether and, if necessary,
initiating treatment with another
agent. The following sections of this
consensus paper summarize key
information from North American
and European labels, clinical studies,
and guidelines for each of the major
antihyperglycemic medications,
relevant to the treatment of adults
with T2DM and CKD.
2. Oral Anti Diabetic Agents in
CKD:
2.1 Metformin:
2.1.1 Metformin must be avoided
when the eGFR <30 ml/
min/1.73 m 2.
2.1.2 Dose Modification is necessary
when eGFR <45 and >30 ml/
min/1.73 m 2
2.1.3 Monitor eGFR every 3 months
The British National formulary
and The Japanese society
of Nephrology state that an
eGFR of ≤30 ml/min/1.73 m 2
mandates discontinuation
of Metformin. The USFDA
states that Metformin is
Prescribing Information
Initial dosing, dose increments, and
maintenance dosage should be conservative
Contraindicated in severe renal failure, dose
reduction necessary starting dose should be
30mg in mild to moderate renal failure
Prescribing Information
<30 <90 - >60 <60 - >30 <30
No dose adjustment
contraindicated when Serum
Creatinine is ≥ 1.5 mg/dl in men
and ≥1.4 mg/dl in women. 19
The current prescribing labels
for metformin use reflect a
more conservative approach
than is seen in clinical practice,
or in most recent diabetes
guidelines. 36
Based on available data, we
recommend that metformin
may be suitable for patients
with eGFR >30 and <60 ml/
min/1.73 m 2, with appropriate
caution and monitoring. Care
m u s t a l wa y s b e t a k e n i n
patients with other risk factors
for lactic acidosis.
2.2 Sulphonylureas
2.2.1 To be avoided in patients
prone to Hypoglycemia
2.2.2 Gliclazide and Glipizide can
be recommended as safer
agents among sulphonylureas.
The summary of Guidelines
and Prescribing information
for the use of Sulphonylureas
in CKD is provided in Table 2.
The NFK-KDOQI recommends
no dose adjustment with
Glipizide and Gliclazide in
CKD stages 3-5. Glimepiride
may need to be started
conservatively at a dose of
1 mg daily and then titrated
to reach targets. Glyburide,
a second generation agents
substantially eliminated
by the kidney, is better
avoided and other agents
a r e t o b e p r e f e r r e d . 19 T h e
glyburide prescribing
29
information though proposes
a conservative approach to
initiation and titration of the
dose in patients with CKD.36-41
Given the propensity of
sulphonylureas to cause
hypoglycemia in patients with
CKD who are already at a high
risk to develop hypoglycemia,
we recommend a watchful
approach in using these
agents. They are to be avoided
in patients with a history
of hypoglycemic episodes.
Gliclazide and Glipizide can
be the better options within
the class of sulphonylureas.
2.3: Thiazolidinediones
2.3.1 Thiazolidinediones can be
used with caution.
2.3.2 These agents are to be avoided
in patients with fluid retention.
The summary of Guidelines and
prescribing information for
the use of Thiazolidinediones
in CKD is provided in Table
3. Available PK data suggest
that there is no difference in
pioglitazone serum half-life
in patients with severe CKD
and those with normal renal
function. 42, 43
Given the elimination
characteristics of pioglitazone,
we recommend that
Pioglitazone can be used with
i n pa t i e nt s w i t h CKD b ut
with caution. The existing
data on fluid retention and
Congestive Heart Failure as
mentioned in the product
leaflets mandate us to restrict
the use of Pioglitazone in
patients with a history of fluid
retention.
2.4 Alpha Glucosidase inhibitors
2.4.1 To be avoided in patients with
eGFR< 30 ml/min/1.73m 2
Wi t h a c a r b o s e , i n c r e a s e d
levels of the parent drug and
metabolites are observed with
CKD, although an increased
risk of hypoglycemia has
n o t b e e n d o c u m e n t e d . 46
Miglitol has greater systemic
absorption that acarbose,with
50–100% of a dose being
absorbed. This drug has
 30 Supplement to Journal of The Association of Physicians of India ■ Published on 1st of Every Month 1st October, 2016
minimal protein binding
and is not metabolized, but
undergoes renal excretion,
with as much as 95% of a dose
recovered in the urine. 47
Prescribing information for
these 2 agents are consistent
with the recommendations
from the KDOQI (Table 4). 48,49
Given the lack of clinical data
for use in this population, we
do not recommend the use of
alpha glucosidase inhibitors
below the eGFR of 30 ml/
min/1.73m 2.
2.5 DPP4 Inhibitors.
2.5.1 D P P 4 i n h i b i t o r s c a n b e
used safely though dose
modifications have to be done
based on eGFR.
The summary of Guidelines
and prescribing information
for the use of DPP4 Inhibitors
in CKD is provided in Table
5. Most DPP-4 inhibitors
(sitagliptin, vildagliptin,
saxagliptin, alogliptin)
are predominantly
excreted by the kidneys.
Thereby, pharmacokinetic
s t u d i e s s h o we d t h a t t o t a l
exposure to the drug is
increased in proportion to
the decline of GFR, leading
to recommendations for
appropriate dose reductions
according to the severity of
CKD. In contrast, linagliptin is
Table 4: Guidelines and Prescribing information for the use of Alpha Glucosidase
Inhibitors in CKD
Agent KDOQI guidelines 20122
eGFR in ml/min/1.72 m
<90 - >60 <60 - >30
Acarbose
Miglitol
  Safe   Cautious Use
Table 5: Guidelines and Prescribing information for the use of DPP4 Inhibitors in CKD
Agent
>50
Sitagliptin 100mg OD
Saxagliptin 5 mg OD
VIldagliptin 50 mg BD
Linagliptin
  Safe
eliminated by a predominantly
hepatobiliary route.
Patients with CKD represent
a specific subpopulation that
may take advantage of using
a DPP-4 inhibitor instead of
a sulphonylurea in order to
reduce the potential risk of
hypoglycaemia. 50
The KDOQI guidelines
2012 and the prescribing
information for these
agents are consistent with
d o s e c h a n g e s . 19 B a s e d o n
t h i s d a t a , we r e c o m m e n d
that DPP4 inhibitors can be
used safely in CKD though
dose modifications may be
necessary.
2.6 SGLT2 inhibitors
2.6.1 Avoid when eGFR <45 ml/
min/1.73m 2 BSA.
These agents have reduced efficacy in
patients with renal impairment.
None of the SGLT2 inhibitors in
use currently need dose adjustment
in patients with mild renal
impairment, and these drugs are
generally not recommended or are
contraindicated in patients with
severe CKD or ESRD.Usage and
dose recommendations in moderate
CKD vary between the labels for
the different agents (canagliflozin,
dapagliflozin, and empagliflozin),
with some agents not recommended
below CrCl of 60 mL/min and others
below 45 mL/min. 55
Prescribing Information
<30 <90 - >60 <60 - >30 <30
<25 ml/
min/1.73m2
<25 ml/ <25 ml/
min/1.73m2 min/1.73m2
  Contraindicated
KDOQI 2012
eGFR (ml/min/1.73 m2)
50-30 <30 >50
50 mg OD 25 mg OD 100mg OD
2.5 mg OD 5 mg OD
50 mg OD 50 mg BD
No dose adjustment
  Cautious Use  
S G LT 2 i n h i b i t o r s h a v e o n l y
recently been approved and have
not been included in many of
the available guidelines. The 2013
AACE guidelines mention that
canagliflozin should not be used if
eGFR is \45 mL/min/ 1.73 m2 , and
the 2015 AACE/ACE update reminds
us that these agents have limited
efficacy in patients with CKD since
they exert their glycemic effects in
the kidney. The 2015 update of the
ADA/EASD position statement state
that the labels have varying renal
restrictions.
Elevations in serum creatinine,
and decreases in eGFR, occurring
during the initial period of clinical
use, have been demonstrated with
all three of the SGLT2 inhibitors, and
seem to be most notable in patients
with moderate CKD. 56-61
Based on the available evidence
with this class of agents, we
recommend that SGLT2 inhibitors
be avoided when the eGFR <45 ml/
min/1.73 m 2. Clinicians also need
to be aware that there is loss of
glycaemic efficacy with deteriorating
renal function while using SGLT2
inhibitors.
Consensus
Recommendation 3: Non-
Insulin Anti Injectables in
CKD:
3.1 GLP1 Analogues
3.1.1 G L P 1 A n a l o g u e s c a n b e
considered when eGFR >30
2
ml/min/1.73 m BSA.
3.1.2 Liraglutide has demonstrated
efficacy and safety in
patients with moderate renal
dysfunction.
Pharmacokinetic studies have
been performed with all of the GLP-1
receptor agonists in patients with
Prescribing Information
50-30 <30
50 mg OD 25 mg OD
2.5 mg OD
50 mg OD
No dose adjustment
Contraindicated
 Supplement to Journal of The Association of Physicians of India ■ Published on 1st of Every Month 1st October, 2016 31

Table 6: Recommendations for the contraindicated or not recommended Exogenous insulin is primarily
use of oral anti diabetic for patients with eGFR\30 mL/ cleared via renal metabolism 73-75 ,
agents in CKD min/1.73 m2. The 2015 AACE/ACE impaired renal function in patients
Agent Recommendation guidelines state that there are no with diabetes can result in
Proposed noted precautions for liraglutide decreased clearance of insulin and,
Metformin Avoid if eGFR 2< 30 in patients with CKD. Lixisenatide, consequently, prolonged exposure.19
ml/min/1.73 m BSA, Albiglutide and Dulaglutide are Diabetes patients with impaired
Dose modification not yet mentioned in the guideline renal function may therefore be at
when eGFR between2 statements. increased risk of hypoglycemia.
30-45 ml/min/1.73 m 76-78
In addition, deterioration of
All GLP-1 receptor agonists may
Monitor eGFR every renal function can lead to increased
be used without dose adjustment in
3stmonths exposure to insulin therapy,
mild CKD. Exenatide should be used
Sulphonylureas 1ndchoice Gliclazide, potentially increasing the risk of
2 choice: Glipizide with caution in patients with eGFR
30–50 mL/min/1.73 m2, and not at all hypoglycaemia.
Avoid in
patients prone to in patients with severe CKD. Some authors recommend
Hypoglycemia We can summarize that there is avoiding intermediate- and long-
Treatment should be general agreement between product acting insulins while others are
individualised. labels and guidelines that the GLP-1 active proponents. The absence of
Thiazolidinediones Can be used with receptor agonists may be used in comparative studies does little to
caution recommend usage, as does the little
mild CKD with no dose adjustment.
To be avoided in For moderate CKD, Exenatide should information available on clinical
patients with fluid consequences for the different types
retention
be used with caution, and in severe
CKD, not used at all. For the GLP-1 of insulin in such patients. 46,79
Alpha Glucosidase Avoid in patients
Inhibitors with eGFR <30 ml/ receptor agonists, which are cleared Impaired renal function in
min/1.73 m2 BSA by general protein catabolism, patients with Diabetes can affect
DPP4 inhibitors Dose to be titrated there are varying recommendations, the pharmacokinetics of some
based on eGFR, safe with the EU/Canada generally not insulin formulations including
recommending use in severe CKD regular Human Insulin and insulin
SGLT2 inhibitors Avoid when eGFR 2 (for which there was limited clinical Lispro.80-82 Insulin Aspart and Insulin
<45 ml/min/1.73 m
BSA. experience), and with no restrictions detemir though have demonstrated
and no dose adjustments in the US unaffected pharmacokinetics.
Loss of efficacy
in reduced renal labels. 55 Published evidence indicates that
function Based on the available evidence Insulin analogs may maintain their
with this class of agents, we pharmacokinetic profiles in this
varying degrees of renal impairment. patient population. 83-86
recommend that GLP1 Analogues
For exenatide (twice daily) which is
can be considered when the eGFR Pharmacokinetic properties
eliminated by glomerular filtration,
>30 ml/min/1.73 m 2 . Liraglutide of insu lin deg lu de c in sub ject s
systemic exposure was increased
has efficacy and safety data from w i t h va r y i n g d e g r e e s o f r e n a l
in patients with moderate or worse
a trial conducted in patients with function; normal, mild, moderate
CKD.63-66 Liraglutide and dulaglutide
moderate renal failure and thus can o r s e ve r e r e n a l i m p a i r m e n t ; o r
are large proteins, which are broken
be considered as a therapeutic option end-stage renal disease (ESRD)
down by general protein catabolism.
in this population. u n d e r g o i n g h e m o d i a l y s i s wa s
Liraglutide showed no increase in
evaluated in 30 patients. The ultra-
systemic exposure in patients with
worsening CKD.68,69 Dulaglutide also
Consensus long pharmacokinetic properties of
showed small increases in systemic Recommendation 4: insulin degludec were preserved
with no statistically significant
exposure that were not clinically Insulins in CKD: differences in absorption or
relevant. 70,71
4.1 Newer Insulin Analogs to clearance, compared with subjects
Liraglutide has been evaluated for with normal renal function. 87
efficacy and safety as an add-on to be preferred as they have
pharmacokinetics unaltered The NFK- KDOQI 2012 guidelines
existing glucose-lowering edications
in CKD including ESRD. do not recommend dose adjustment
in patients with inadequately
4.2 Insulin to be initiated at small with long acting insulins such as
controlled type 2 diabetes and
doses with strict monitoring Insulin Glargine, Insulin Detemir,
moderate renal impairment. No
Neutral Protamine Hagedorn or
changes in renal function were 4.3 Insulin dose needs to be titrated rapid acting insulins such as Regular
observed. No difference in to requirements to reduce the Human Insulin, Insulin Aspart,
hypoglycemic episodes was observed risk of Hypoglycemia Insulin Lispro or Insulin Glulisine. 19
between treatment groups. 72
4.4 Insulin pumps are an option The prescribing information for
A l l t h e r e v i e we d g u i d e l i n e s for suitable patients. these insulin formulations including
state that exenatide is either
32 Supplement to Journal of The Association of Physicians of India ■ Published on 1st of Every Month 1st October, 2016

Table 7: Recommendations for the Table 8: Recommendations for the use of Insulins in CKD
use of Non Insulin Injectable
Insulin Recommendation Proposed
Anti Diabetic Agents in CKD
Glargine
Agent Recommendation Detemir
Proposed
Neutral Protamine
GLP1 analogs Not recommended when
Hagedorn (NPH) • Newer Insulin Analogs may be preferred as they have
eGFR <30 ml/min/1.73 m2
BSA. Regular pharmacokinetics unaltered in CKD including ESRD.

Efficacy in CKD better • Initiate at small doses with strict monitoring

Aspart
than other oral agents • Dose needs to be titrated to requirements to reduce risk of
Lispro
Hypoglycemia
newer analogues such as Insulin Glulisine
• Insulin pumps are an option for suitable patients.
Degludec and co-formulation of Biphasic Insulin
Insulin Degludec with Insulin Aspart Aspart
recommend that dose adjustment Insulin Degludec +
may be necessary. 88-97 Insulin Aspart

Based on the available evidence,
we recommend Newer Insulin
Analogs to be preferred over
regular human insulin as they have
pharmacokinetics unaltered in CKD
including ESRD. We recommend that
Insulin be initiated at small doses
with strict monitoring. The dose
needs to be titrated to requirements
to reduce the risk of Hypoglycemia.
Hypoglycaemic pumps can be an
option in suitable settings.
Conclusion
Use of Anti-Diabetic agents in
patients with renal insufficiency
pose significant challenges due to
lack of a clear consensus. A review
of existing evidence including
guidelines, published literature
and package inserts helped draft
this consensus recommendations
(Tables 6-8). These recommendations
can assist clinicians make informed
choices while managing patients
with chronic kidney disease.
Acknowledgements
We thank the consensus group
members; B Seetharam, Y Sadasiva
Rao, G Surendra, Sanjay Jain,
Latif Khan, Mary John, Bikash
Bhattacharya, Debojit Maji, Neeraj
K Singh, Bhuvanapriya, Biju Mosses,
Manoj Kumar Sha, PP Mohanan for
their valuable contributions.
The authors would like to thank
the organisers of National Insulin
Summit 2015.
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