This document discusses a 63-year-old man with type 2 diabetes and chronic kidney disease who presents with increased fatigue and hypoglycemia. He has a history of diabetes for 11 years and hypertension for 6.5 years. Laboratory tests show uncontrolled diabetes with early declining renal function. His treatment is modified by substituting gliclazide for glimepiride and continuing linagliptin based on his estimated glomerular filtration rate. Studies show linagliptin improves glycemic control in patients with kidney disease without worsening renal function or increasing hypoglycemia risk. After treatment changes, his blood sugar, albuminuria, and kidney function show improvement at 3 and 6 month follow ups.

1. Chronic Kidney Disease with Type 2 Diabetes Mellitus

2. CASE 1
• Patient Sawami, aged 63 years retired from government office working in firm
visits his primary care physician with complaints of increased fatigue, also 2
episodes oh hypoglycemia.
• He was K/C/O of
• Diabetes since 11 years
• Hypertension since 6.5 years

3. Patient Profile
• 60 F - DM2 x 11 yrs, HT x 6.5 yrs
• Strong family history of Diabetes - Brother, Mother died of CKD
• Examination- Obese, BMI 30 kg/m2
• BP 134/86 mmHg
• Systemic Exam - NAD
• Poor compliance - Morning walk x 30 min - General weakness
• SMBG - FPG 160 -175 mg/dl, PPG 235-250 mg/dl
• Patient has reported mild hypoglycemia

4. Current Treatment
• Metformin 1500 mg/d
• Glimepiride 2 mg OD
• Sitagliptin 100 mg OD
• Aspirin 75 mg
• Telmisartan 40 + Amlodipine 5mg OD

5. Laboratory Investigations
• FPG 175 mg/dl , PPG 150 mg/dl, HbA1c 9.0%, Urine R/M: N
• TC 185 mg/dl, LDL: 112 mg/dl, TG: 140, HDL: 72 mg/dl
• B. Urea 24.5, UACR: 435 mg/g, eGFR: 51 mL/min/1.73m2
• Serum albumin 3.3 g/dl
• LFT - Normal
• Chest X-ray - NAD , USG Abdomen - Normal
• ECG - Sinus Tachycardia

6. Diagnosis
Uncontrolled Type 2 Diabetes with high Risk of ASCVD and
Declining Renal Function

7. Improvement of Microalbuminuria by Linagliptin (UACR<30 mg/dl)
% of improvement in microalbuminuria (UACR<30
mg/g) in Linagliptin group was significantly higher
than that of the control group during 24 weeks of
intervention
• A double-blind randomized placebo-controlled
(n=92)
• Linagliptin 5 mg OD for 24 weeks
Karimifar M et al. Sci Rep. 2023 Mar 1;13(1):3479.

8. Efficacy of Linagliptin in Patients with T2DM and Renal Dysfunction
MARLINA-T2D Trial
• a 24-week, randomized, double-blind,
placebo-controlled, phase 3b clinical trial
• n=360 for 24 weeks
Conclusion: The MARLINA-T2D study found that Linagliptin improved glycaemic control in
individuals with type 2 diabetes and early stages of diabetic kidney disease
Groop PH et al. Diabetes Obes Metab. 2017 Nov;19(11):1610-1619.

9. Oxidative Stress and
Diabetic Kidney Disease
Oxidative stress is linked with metabolic changes and
alterations in renal haemodynamics.
Nina Vodošek Hojs et al. Antioxidants 2020, 9(10), 925

10. Effect of Linagliptin on Oxidative Stress Markers in T2DM
 A single-center single-arm interventional study (n=30)
 Linagliptin 5 mg for 3 Months
 Following linagliptin treatment,
• Serum MDA-LDL
• Serum HbA1c
• Urinary L-FABP levels significantly decreased
 Urinary 8-OHdG tended to decrease
Hisashi Makino et al. Diabetology International (2019) 10:148–152

11. Date of Download: 8/2/2023
1. Diabetes Care. 2020;43(11):2889-2893. doi:10.2337/dc20-0902
2. Diabetologia (2016) 59:2579–2587
Renal hemodynamic and tubular effects of linagliptin and glimepiride after 8 weeks of
treatment. Mean ± SEM (A–C and F), median [IQR] (D and E), and baseline-corrected mean
difference (95% CI). Multivariable linear regression models were used to examine baseline-
corrected linagliptin-induced effects compared with glimepiride. Paired t tests (A–C and F) or
Wilcoxon signed rank tests (D and E) were used for within-group comparisons. Significant
differences are indicated in boldface type. PAH, para-aminohippuric acid; Wk, week.
Compared to Glimepiride,
• Linagliptin had no significant impact on fasting GFR
and ERPF. 1
Compare to Glimepiride, Linagliptin tended to
• Reduce UACR by 26% from baseline
• No between-group differences were observed.1
This neutral effect of Linagliptin on
• GFR and ERPF is consistent with previous placebo-
controlled trials involving T2DM patients without
renal impairment. 2
Effects of DPP-4 Inhibitor Linagliptin Versus Sulfonylurea Glimepiride as Add-on to
Metformin on Renal Physiology in Overweight Patients With Type 2 Diabetes (RENALIS):
A Randomized, Double-Blind Trial
GFR: Glomerular Filtration Rate
ERPF: Effective Renal Plasma Flow
UACR: urinary albumin-to-creatinine ratio

12. Effects of Linagliptin on Cardiovascular and Kidney
Outcomes in People With Normal and Reduced
Kidney Function: Secondary Analysis of the
CARMELINA Trial
Linagliptin vs. placebo effect on 3P-MACE (major
adverse cardiovascular events): No significant
difference (HR 1.02 [95% CI 0.89, 1.17])
Linagliptin vs. placebo effect on secondary
kidney outcome: No significant difference (HR
1.04 [95% CI 0.89, 1.22])
Albuminuria progression reduced with
linagliptin regardless of eGFR
HbA1c levels decreased with linagliptin without
increasing hypoglycemia risk
Adverse events (AEs) balanced among groups overall
and across eGFR categories
Diabetes Care 2020;43(8):1803–1812
Study population:
• 6,979 subjects, mean age 65.9 years
• eGFR 54.6 mL/min/1.73 m², 80.1% with albuminuria
• Follow-up duration: 2.2 years
Overall effects on eGFR (MDRD) slope from baseline to last value on treatment and by
eGFR category G ≤ 2 to ≥ G4 for linagliptin (Lina) vs. placebo (pbo)

13. 2 year study: Linagliptin was non-inferior to
glimepiride in treatment effect1
Rate of patients achieving HbA1c
target <7%
75.6 76.4
0
20
40
60
80
100
Linagliptin Glimepiride
0.5
0
-0.5
-1.0
-1.5
Adjusted
mean change
in HbA1c (%)
from baseline
at week 104
n
Mean baseline
HbA1c, percent
-0.60 -0.60
7.7
7.7
Rate of patients achieving HbA1c
target <7%
271 233
Gallwitz B., et al. ADA 2011 Late Breaker 39-LB
Linagliptin vs glimepiride2 p <0.0001*

14. Why substituted Glimepiride with Gliclazide in
addition to Linagliptin?
Is there any benefits with Gliclazide
Linagliptin !!!

15. Effectiveness and safety of Gliclazide and
Linagliptin switched from Glimepiride
J Endocr Soc. 2021 May 3; 5(Suppl 1): A407–A408.

16. Effectiveness and safety of Gliclazide and
Linagliptin switched from Glimepiride
T2DM patients with stage 1–3 CKD
Mean eGFR: 50.4 ± 8.56 ml/min/1.73 m2
Inadequately controlled with glimepiride (mean dose 3.24mg) for the last 3 months
J Endocr Soc. 2021 May 3; 5(Suppl 1): A407–A408.
Objective:
• To assess the efficacy and safety of
• Switching from glimepiride to Gliclazide MR in combination with linagliptin, in T2DM patients
with kidney disease
Patient Selection:

17. Patient Selection and Treatment:
• Switched to gliclazide MR with an appropriate
equivalent dose.
• Gliclazide dose titrated by 30 mg every 15 days
to target PPG ≤180 mg/dL.
• Follow-up for 24 weeks,
• Assessing changes in glycemic control,
hypoglycemia risk, and renal function
parameters.
79%
14%
7%
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
Linagliptin Sitagliptin Vildagliptin
Continued DPP-4 inihitors therapy (%)
Effectiveness and safety of Gliclazide and
Linagliptin switched from Glimepiride
J Endocr Soc. 2021 May 3; 5(Suppl 1): A407–A408.

18. Effectiveness and safety of Gliclazide and
Linagliptin switched from Glimepiride
• 218 eligible patients (110 female & 108 male) with CKD (stages 1–3) participated.
J Endocr Soc. 2021 May 3; 5(Suppl 1): A407–A408.
• Baseline characteristics:
• Mean age: 62.94 ± 8.72 years
• Body weight: 67.9 ± 9.33 kg
• Baseline HbA1c: 8.51 ± 0.81%
• FPG: 148.53 ± 16.72 mg/dL
• PPG levels: 202 ± 18.45 mg/dL
• Mean eGFR: 50.49 ± 8.56 ml/min/1.73 m2
• UACR: 154.34 mg/g

19. Results: Switching from glimepiride to
Gliclazide
• Gliclazide MR initiated, replacing glimepiride, with appropriate dosing.
• At 24-week follow-up:
• Significant reductions in HbA1c (-0.63%), FPG (-10.33 mg/dL), and PPG levels (-30.04 mg/dL)
(p< 0.001).
• Notable reduction in overall hypoglycemia events (22.25%).
• Improvements in renal function: eGFR increased by +1.77 ml/min/1.73 m2, and albuminuria
decreased by -45.56 mg/g.
J Endocr Soc. 2021 May 3; 5(Suppl 1): A407–A408.

20. Effectiveness and safety of Gliclazide and
Linagliptin switched from Glimepiride
Conclusion:
• This study demonstrates the clinical effectiveness and safety of gliclazide MR in
combination with DPP-4 inhibitors, such as linagliptin, as a viable alternative to
glimepiride in T2DM patients with chronic kidney disease.
J Endocr Soc. 2021 May 3; 5(Suppl 1): A407–A408.

21. Modified Current Treatment based on eGFR
• Metformin 1000 mg SR + Gliclazide 30 mg XR as FDC OD
• Linagliptin 5 mg OD
• Aspirin 75 mg
• Telmisartan 40
• Clorthalidone 12.5mg OD

22. Follow-up Results After 3 Months & 6 Months
FPG 145 mg/dl , PPG 130 mg/dl, HbA1c 8.2%, Urine R/M: N
TC 176 mg/dl, LDL: 100 mg/dl, TG: 128, HDL: 80 mg/dl
3 Months
FPG 112 mg/dl , PPG 122 mg/dl, HbA1c 8.0%, Urine R/M: N
UACR: 398, TC 170 mg/dl, LDL: 97 mg/dl, TG: 128, HDL: 82
mg/dl
6 Months

23. Thank You!