Research on Optimal Strategy of Hypoglycemic Therapy for Cirrhosis With Diabetes

Phase 3

Recruiting

• Conditions: Diabetes; Liver Cirrhosis
• Interventions: Drug: Insulin Degludec and Insulin Aspart

• Registration Number: NCT05641337
• Lead Sponsor: Huashan Hospital

Brief Summary

Poor blood glucose control in liver cirrhosis can aggravate the poor prognosis of patients. Under the background of the increasing number of liver cirrhosis patients with metabolic abnormalities, how to optimize treatment is particularly important. The traditional treatment of diabetes at the stage of liver cirrhosis is limited to insulin intensive therapy, but the incidence of hypoglycemia is high, blood sugar fluctuates greatly, and multiple injections are required. Research shows that insulin therapy has an increased overall mortality compared with non insulin therapy. We used metformin,Ryzodeg and an oral DDP IV enzyme inhibitor as the core combination according to the special pathological mechanism of elevated blood glucose in liver cirrhosis . After preliminary experiments, we found that the program was stable and was not easy to have hypoglycemia, and there was no traditional risk of lactic acid poisoning caused by metformin. We designed an open randomized controlled clinical study, Compared with the traditional insulin intensive treatment scheme, this new combination scheme was compared whether it could improve the blood glucose level, the incidence of hypoglycemia and lactic acid level, the incidence of cirrhosis complications, and the long-term survival rate of liver disease. This study is helpful to optimize the hypoglycemic treatment of cirrhosis with diabetes, and improve the blood glucose and long-term prognosis, The positive evidence of this study contributes to the consensus or guidelines for the treatment of cirrhosis with diabetes.

Detailed Description

Cirrhosis with diabetes refers to the increase of blood sugar in cirrhosis, including cirrhosis before or after diabetes. It has a special pathophysiological mechanism that liver factors participate in blood glucose regulation. Poor blood glucose control in liver cirrhosis can aggravate the poor prognosis of patients. Under the background of the increasing number of liver cirrhosis patients with metabolic abnormalities, how to optimize treatment is particularly important. The traditional treatment of diabetes at the stage of liver cirrhosis is limited to insulin intensive therapy, but the incidence of hypoglycemia is high, blood sugar fluctuates greatly, and multiple injections are required. Research shows that insulin therapy has an increased overall mortality compared with non insulin therapy. We used metformin, ,Ryzodeg and an oral DDP IV enzyme inhibitor as the core combination according to the special pathological mechanism of elevated blood glucose in liver cirrhosis from multiple links. After preliminary experiments, we found that the program was stable and was not easy to have hypoglycemia, and there was no traditional risk of lactic acid poisoning caused by metformin. We designed an open randomized controlled clinical study, Compared with the traditional insulin intensive treatment scheme, this new combination scheme was compared whether it could improve the blood glucose level, the incidence of hypoglycemia and lactic acid level, the incidence of cirrhosis complications, and the long-term survival rate of liver disease. This study is helpful to optimize the hypoglycemic treatment of cirrhosis with diabetes, and improve the blood glucose and long-term prognosis of such patients, The positive evidence of this study contributes to the consensus or guidelines for the treatment of cirrhosis with diabetes.

Study Timeline

• Study Start: 2022-10-01
• Status Verified: 2022-11
• Study First Submitted: 2022-11-06
• Study First Submitted QC: 2022-11-29
• Last Update Submitted: 2022-11-29
• Study First Posted: 2022-12-07
• Last Update Posted: 2022-12-07
• Primary Completion: 2025-12-30
• Study Completion: 2025-12-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 184

Inclusion Criteria

• Liver cirrhosis
• Age 18-70 years
• Patients with elevated blood sugar who meet the diabetes standard or have been treated with hypoglycemic drugs
• random finger or venous serum blood glucose more than 14 mmol/L

Exclusion Criteria

• Those unwilling to participate or unable to cooperate;
• Child-pugh score is greater than 12;
• Glomerular filtration rate<60ml/min/1.73m2;
• Patients with cardiac insufficiency;
• Patients with asymptomatic hypoglycemia;
• Pregnant patients were excluded;
• Patients with advanced liver cancer;
• Blood pressure is less than 90/60mmHg;
• Chronic liver disease plus acute or subacute liver failure;
• Patients with drug induced blood glucose disorder, such as glucocorticoids, contraceptives, etc;
• fingertip oxygen saturation less than 95% without oxygen inhalation;
• Autoimmune liver cirrhosis is currently taking hormone.
• Type 1 diabetes.
• Pancreatogenic diabetes, such as primary hemochromatosis, hepatolenticular degeneration, alcoholic pancreatitis, autoimmune diseases involving the pancreas, etc.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
group with new combination therapy	Insulin Degludec and Insulin Aspart	The hypoglycemic scheme of the experimental group was that the initial dose of Insulin Degludec and Insulin Aspart was 0.3U/kg multiplied by the patient's weight, plus 5 mg of linagliptin and 0.5 g of metformin three times a day.
group with intensive insulin therapy	Insulin Degludec and Insulin Aspart	group was treated with intensive insulin therapy.The initial total amount of insulin is 0.5U/kg, of which 40% is basal insulin and 20% is aspart insulin before three meals

Primary Outcome Measures

Name	Time	Method
Blood lactic acid level	two week	Blood lactic acid level
time in range	two weeks	time in range
Compound adverse events	two week	includetimes of hypolgycemia attack，severe hypoglycemia attack and serum lactic acid more than 2.2 mmol/L, complications of liver cirrhosis within two week

Secondary Outcome Measures

Name	Time	Method
Time above range	two weeks	Time above range
Time below range	two weeks	Time below range
three month mortality	three months	three month mortality
Six month mortality	six months	Six month mortality
mean blood glucose	two weeks	mean blood glucose
Glycated Albumin	two week	Glycated Albumin
Incidence rate of complications of liver cirrhosis within three months	three months	Incidence rate of complications of liver cirrhosis within three months
Incidence rate of complications of liver cirrhosis within six months	six months	Incidence rate of complications of liver cirrhosis within six months
Blood lactic acid	two weeks	Blood lactic acid

Trial Locations

Locations (1)

Xiaolong Zhao; 🇨🇳 Shanghai, Shanghai, China