Research on Optimal Strategy of Hypoglycemic Therapy for Cirrhosis With Diabetes

Study Overview
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Brief Summary
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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
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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.

Official Title
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Research on Optimal Strategy of Hypoglycemic Therapy for Cirrhosis With Diabetes

Conditions
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Liver Cirrhosis, Diabetes

Intervention / Treatment
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* Drug: Insulin Degludec and Insulin Aspart


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: group with new combination therapy<br>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. | Drug: Insulin Degludec and Insulin Aspart<br>* 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. The control group was treated with traditional four needle insulin.<br>* Other names: linagliptin;|
| Active Comparator: group with intensive insulin therapy<br>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 | Drug: Insulin Degludec and Insulin Aspart<br>* 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. The control group was treated with traditional four needle insulin.<br>* Other names: linagliptin;|

What is the study measuring?
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Primary Outcome Measures

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

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| mean blood glucose | mean blood glucose | two weeks | 
| Time above range | Time above range | two weeks | 
| Time below range | Time below range | two weeks | 
| Blood lactic acid | Blood lactic acid | two weeks | 
| Glycated Albumin | Glycated Albumin | two week | 
| three month mortality | three month mortality | three months | 
| Six month mortality | Six month mortality | six months | 
| Incidence rate of complications of liver cirrhosis within three months | Incidence rate of complications of liver cirrhosis within three months | three months | 
| Incidence rate of complications of liver cirrhosis within six months | Incidence rate of complications of liver cirrhosis within six months | six months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Liver cirrhosis, diabetes, time in range, insulin intensive therapy, new combination therapy