NCT07439536

Dose Optimization of Sitagliptin and Duloxetine in Diabetic Cirrhosis

Evaluation of Model-Guided Dose Adjustment of Sitagliptin and Duloxetine Across Child-Pugh Classes Compared to Non-Cirrhotic Diabetic Patients

• Status: Completed
• Phase: Phase 4
• Study type: Interventional
• Enrollment: 64 (actual)
• Sponsor: Kafrelsheikh University · Academic / Other
• Sex: All
• Age: 18 Years – 18 Years
• Healthy volunteers: Accepted

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.

Detailed description

This study was a prospective, interventional, two-part pilot clinical study conducted over 3 months on Egyptian cirrhotic patients with diabetes mellitus and diabetic neuropathy. Adult patients aged \>18 years with confirmed liver cirrhosis, concomitant diabetes mellitus and diabetic neuropathy were eligible for inclusion. Patients were experienced acute episodes of disease associated with deterioration of hepatic function within 2 months prior to screening, and received concomitant medications known to strongly interact with the study drugs were excluded. In part 1: Sitagliptin dosing was determined based on Simcyp -generated predictions and clinical assessment. 100mg,100 mg, 50 mg, and 50 mg received by control, CP-A, CP-B, and CP-C cirrhosis patients, respectively, orally once daily. In part 2: Duloxetine dosing was determined based on Simcyp-generated predictions and clinical assessment. 60 mg ,30 mg received by control, and CP-A cirrhotic patients orally once daily, respectively. 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

Type	Name	Description
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.

Timeline

• Start date: 2024-07-01
• Primary completion: 2025-07-01
• Completion: 2025-10-01
• First posted: 2026-02-27
• Last updated: 2026-02-27

Locations

1 site across 1 country: Egypt