Diabetic Nephropathy and

Chronic Renal FailureAnna Hemens

Background

CKD Stage 1 Kidney damage with normal or GFR ≥90 Treatment of comorbid conditions, slow progression, CVD risk reduction

CKD Stage 2 Kidney damage with mild ↓ GFR 60-89 Estimating progression

CKD Stage 3 Moderate↓ GFR 30-59Evaluating and treating complications

CKD Stage 4 Severe ↓ GFR 15-29Preparation for kidney replacement therapy

CKD Stage 5 Kidney Failure <15Kidney replacement therapy (if uremia present and patient consents)

Chronic Kidney Disease

Diabetic NephropathyFirst sign microalbuminuria UKPDS 38% albuminuria, 29% renal impairment

after 15yrs follow up (Retnakaran et al, 2006)Increased risk factors:

Systolic hypertension Waist circumference Previous CV disease Smoking Indian-Asian ethnicity

UKPDS Intensive diabetes therapy and BP control <130/80 reduces risk of microalbuminuria and nephropathy in diabetic individuals

AdherenceMavis• 64 yrs old; IHD, HTN, COPD, T2DM• Metformin 500 mg TDS, Gliclazide

80mg BD• Ramipril 10mg OD nocte, Atorvastatin

40mg OD nocte• HBAIC 58• Weight 68kg; BMI 28

AdherenceLifestyle, distress, treatmentVariable strategies (Sapkota et al, 2015)Increased adherence = improvement HBA1C

(Schectman et al, 2002)Sitagliptin (Plosker, 2014)

Low risk hypoglycaemic attacksOnce dailyGive throughout renal diseaseLow weight gain

DIAB-1150856-0000

Therapeutic Indications of DPP-4 Inhibitors

Indication sitagliptin1 saxagliptin2

linagliptin▼3

vildagliptin4

alogliptin▼5

1st Line Monotherapy (if metformin is contraindicated or not tolerated)

√ √ √ √

2nd Line Add on to metformin √ √ √ √ √

Add on to SU √ √ √ √

Add on to PPAR √ √ √ √

3rd Line Add on to metformin + SU

√ √ √ √

Add on to metformin + PPAR

√ √

Insulin Add on to insulin +/- metformin

√ √ √ √ √

DIAB-1150856-0000

DPP-4 inhibitors in Renal ImpairmentDegree of

renal impairment

sitagliptin1 saxagliptin2 linagliptin▼3 vildagliptin4 alogliptin▼5

Mild CrCl ≥50ml/min

100mg 5mg 5mg 50mg BD 25mg

Moderate CrCl ≥30 to <50ml/min

50mg 2.5mg 5mg 50mg OD 12.5mg

SevereCrCl <30ml/min

25mg 2.5mg 5mg 50mg OD 6.25mg

ESRD 25mg Not recommended

5mg 50mg OD with caution

6.25mgExperience in

patients requiring renal dialysis is

limited; not studied in

peritoneal dialysis.

1. Januvia SPC, April 2015 2. Saxagliptin SPC April 2015 3. Linagliptin SPC April 20135 4. Vildagliptin SPC April 2015 5. Alogliptin SPC April 2015. DIAB-1179806-0000

Sitagliptin Efficacy is Similar Across the Spectrum of Renal Function (1-

Year Data)Metformin + Sitagliptin 100 mg1 Metformin + Sitagliptin 50 mg2 Metformin + Sitagliptin 25 mg3

Chan

ge in

HbA

1c F

rom

Bas

elin

e, %

n=411n=382 n=135 n=142 n=59n=62

1. Nauck MA et al. Diabetes Obes Metab. 2007;9(2):194–205.2. Arjona Ferreira JC et al. Diabetes Care. 2013;36:1067–1073.3. Arjona Ferreira JC et al. Am J Kidney Dis. 2013;61:579–587.

P=NS for all between-groups comparisons–

–

–

–

–

–

–

–

DIAB-1179806-0000

Sitagliptin vs. glipizide in patients with T2D and Moderate to severe chronic renal insufficiency: HbA1c Results at 54 Weeks1

Per Protocol Population

LS=least squares; SE=standard error; CI=confidence interval.aSitagliptin (n=135), Glipizide (n=142) at week 54. bMean dose of glipizide was 7.7 mg per day.Adapted with permission from Arjona Ferreira JC.1

1. Arjona Ferreira JC et al. Diabetes Care. 2013; 36:1067-1073

LS M

ean

(±SE

) Cha

nge

From

Bas

elin

e, %

0 6 12 18 24 30 36 42 48 54Week

sitagliptina glipizidea,b

−1.0−0.9−0.8−0.7−0.6−0.5−0.4−0.3−0.2–0.10.0

Baseline HbA1c; sitagliptin = 7.8%; glipizide = 7.8%

−0.6%

−0.8%

LS Mean Between-Group Difference (95% CI):

–0.1% (–0.3, 0.1)Noninferiority: upper bound of the 95% CI around the between-group difference <

0.4%.

DIAB-1179806-0000

Questions? Anna.hemens@nhs.net

WWW.KIDNEY.ORG.UK

WWW.BRITISHKIDNEY-PA.CO.UK

WWW.RENAL.ORG

Diabetes Control and Complications Trial (DCCT) Research Group (1993) The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin- dependent diabetes mellitus. N Engl J Med 329: 977–86

Retnakaran R, Cull CA, Thorne KI (2006) Risk factors for renal dysfunction in type 2 diabetes: U.K. Prospective Diabetes Study. Diabetes 74: 1832–9

Schloot NC, Haupt A, Schutt M et al (2015) Risk of Severe Hypoglycaemia in sulphonyurea-treated patients from diabetes centers in Germany/Ausria; How big is the problem? Which patients are at risk? Diabetes Metab Res Rev 32, 316-24

Ou SM, Shih CJ, Chao PW et al (2015) Effects on clinical outcomes of adding dipeptidy peptidase-4 inhibitors versus sulfonyureas to metformin therapy in patients with type 2 diabetes mellitus Ann Intern Med 163; pp663-72