Dose Optimization of Sitagliptin and Duloxetine in Diabetic Cirrhosis

Summary

This study was a prospective, interventional, two-part pilot clinical study conducted over 3 months on cirrhotic patients with diabetes mellitus and diabetic neuropathy, evaluating the real-world applicability of selected PBPK-guided dosing regimens. Patients were stratified according to Child-Pugh class (CP-A , CP-B, and CP-C) in case of sitagliptin and CP-A in duloxetine at doses corresponding to the closest commercially available strengths to Simcyp®-optimized doses.

Clinical evaluation included glycemic parameters(HbA1C,fasting blood glucose,2-hr post prandial glucose level) and pain reduction. Routine laboratory investigations were conducted to assess efficacy and safety and included liver function tests (serum albumin, total bilirubin, alanine aminotransferase \[ALT\],and aspartate aminotransferase \[AST\]), kidney function tests (serum creatinine and blood urea nitrogen \[BUN\]),and CBC.

Conditions

• Liver Cirrhosis With Diabetes

Interventions

DRUG

Sitagliptin (Januvia)

Diabetic patients with Child-Pugh class A hepatic cirrhosis receiving 100 mg model -informed adjusted dose of sitagliptin. Sitagliptin is an oral dipeptidyl peptidase-4 (DPP-4) inhibitor used in conjunction with diet and exercise to improve glycemic control in patients with type 2 diabetes mellitus. The effect of this medication leads to glucose dependent increases in insulin and decreases in glucagon to improve control of blood sugar.

DRUG

Sitagliptin (JANUVIA®)

Diabetic patients with Child-Pugh class C hepatic cirrhosis receiving 50 mg model -informed adjusted dose of sitagliptin. Sitagliptin is an oral dipeptidyl peptidase-4 (DPP-4) inhibitor used in conjunction with diet and exercise to improve glycemic control in patients with type 2 diabetes mellitus. The effect of this medication leads to glucose dependent increases in insulin and decreases in glucagon to improve control of blood sugar.

DRUG

Sitagliptin (JANUVIA®)

Diabetic patients with Child-Pugh class B hepatic cirrhosis receiving 50 mg model -informed adjusted dose of sitagliptin. Sitagliptin is an oral dipeptidyl peptidase-4 (DPP-4) inhibitor used in conjunction with diet and exercise to improve glycemic control in patients with type 2 diabetes mellitus. The effect of this medication leads to glucose dependent increases in insulin and decreases in glucagon to improve control of blood sugar.

DRUG

Sitagliptin (JANUVIA®)

Diabetic patients without hepatic cirrhosis receiving the standard recommended dose of 100 mg sitagliptin. Sitagliptin is an oral dipeptidyl peptidase-4 (DPP-4) inhibitor used in conjunction with diet and exercise to improve glycemic control in patients with type 2 diabetes mellitus. The effect of this medication leads to glucose dependent increases in insulin and decreases in glucagon to improve control of blood sugar.

DRUG

Duloxetine (60 mg) once daily

Diabetic patients without hepatic cirrhosis receiving the standard recommended dose of 60 mg Duloxetine. Duloxetine is a dual serotonin and norepinephrine reuptake inhibitor, It has since received approval for a variety of indications including the treatment of neuropathic pain.

DRUG

Duloxetine 30mg once daily

Diabetic patients with peripheral diabetic neuropathy and Child-Pugh class A hepatic cirrhosis receiving 30 mg model -informed adjusted dose of duloxetine. Duloxetine is a dual serotonin and norepinephrine reuptake inhibitor, It has since received approval for a variety of indications including the treatment of neuropathic pain.

Sponsors & Collaborators

• Kafrelsheikh University

  lead OTHER

Principal Investigators

• Noha Mahmoud ELkhodary, PhD · Clinical Pharmacy Department, Faculty of Pharmacy, Kafrelsheikh University

• Aya Emad Fouda, MSc in Clinical Pharmacy · Clinical Pharmacy Department, Faculty of Pharmacy, Kafrelsheikh University

Study Design

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

18 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2024-07-01

Primary Completion

2025-07-01

Completion

2025-10-01

Countries

• Egypt

Study Locations