Effects of Sequential Treatment Based on Lina/MET After Short-term Intensive Insulin in Newly Diagnosed Type 2 Diabetes

NCT03194945 | Completed Phase 4 DMC

• 1 other identifier: 2016146
• Study Type: interventional
• Target: 412
• Locations: 1 country
• Sites: 1

Brief Summary

Short-term intensive insulin therapy(SIIT) is able to reverse β cell dysfunction and induce glycemic remission in patients with newly diagnosed type 2 diabetes. However, proportion of patients with response gradually decreases over time. There is no consensus on which treatment should be given in order to maintain the benefit in glycemic control and β cell recovery. In this multi-center, randomized, controlled study, effects of various sequential treatments ( metformin, linagliptin and combined with both drugs) on long-term blood glucose control as well as preservation of β cell function after SIIT were investigated. In total, 412 patients with newly diagnosed type 2 diabetes who meet the inclusive criteria will be enrolled in eight centers in China. After baseline assessments, all patients will be treated with insulin pump to achieve and maintain euglycemia for 2 weeks. After completion of intensive treatment, insulin pump will be stopped. Different treatments will be applied to patients for 48 weeks according to randomization: Group A: Linagliptin 5 mg Qd + Metformin 0.5 g bid; Group B: Linagliptin 5 mg Qd; Group C: Metformin 0.5 g bid; Group D: No oral drugs. Primary endpoint is proportion of patients achieving glycosylated hemoglobin A1C \<7% at the end of the study. Secondary endpoints include proportion of patients achieving glycosylated hemoglobin A1C \<6.5% at the end of study; differences in β-cell function , insulin sensitivity, GLP-1 and glucagon secretion among treatment groups, and differences in adverse events among treatment groups.

Conditions

Type 2 Diabetes Mellitus

Keywords

Type 2 diabetes mellitus; Continuous subcutaneous insulin infusion; Metformin; Linagliptin

Outcome Measures

Primary Outcomes (1)

• proportion of subjects with optimal glycemic control

  proportion of patients achieving glycosylated hemoglobin A1C \<7% at the end of sequential treatment in each treatment group.

  48 weeks

Secondary Outcomes (4)

• proportion of subjects with excellent glycemic control

  48 weeks

• Change of β cell function

  48 weeks

• Change of insulin sensitivity

  48 weeks

• Incidence of adverse events

  48 weeks

Study Arms (4)

Linagliptin plus metformin

ACTIVE COMPARATOR

CSII followed by Linagliptin 5 mg Qd + Metformin 0.5 g bid for 48 weeks

Drug: CSII followed by Lina+MET

Linagliptin

ACTIVE COMPARATOR

CSII followed by Linagliptin 5mg Qd for 48 weeks

Drug: CSII followed by Lina

Metformin

ACTIVE COMPARATOR

CSII followed by Metformin 0.5 bid for 48 weeks

Drug: CSII followed by MET

Lifestyle alone

ACTIVE COMPARATOR

No OHA is given after CSII

Drug: CSII alone

Interventions

CSII followed by Lina+MET DRUG

short-term intensive CSII followed by Linagliptin 5mg qd and Metformin 0.5g bid for 48 weeks

Also known as: CSII+Lina+Met

Linagliptin plus metformin

CSII followed by Lina DRUG

short-term intensive CSII followed by Linagliptin 5mg qd for 48 weeks

Also known as: CSII+Lina

Linagliptin

CSII followed by MET DRUG

short-term intensive CSII followed by Metformin 0.5g bid for 48 weeks

Also known as: CSII+Met

Metformin

CSII alone DRUG

No OHA is given after short-term intensive CSII

Also known as: CSII

Lifestyle alone

Eligibility Criteria

• Age: 20 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with type 2 diabetes who have never received any hypoglycemic treatment；
• Fasting plasma glucose (FPG) between 7.0 mmol/l (126 mg/dl) and 16.7 mmol/l (300 mg/dl);
• glycosylated hemoglobin A1C≥8.5%;
• Aged between 20 and 70 years 5） body mass index (BMI) 22-35 kg/m2.

You may not qualify if:

• Type 1 diabetes or special type of diabetes;
• Acute complications of diabetes (including DKA, HHS and lactic acidosis)
• Serious microvascular complications: proliferative stage of retinopathy; urine AER \>300 mg/g or urine protein positive, quantification \>0.5 g/d; uncontrolled painful diabetic neuropathy and significant diabetic autonomic neuropathy;
• Severe macrovascular complications: acute cerebrovascular accident, acute coronary syndrome, vascular intervention for peripheral arterial disease or amputation requiring hospitalization within 12 months prior to enrollment;
• Persistently increased blood pressure \>180/110 mmHg;
• Blood creatinine clearance less than 50 ml/min, alanine aminotransferase ≥2.5×upper limit of normal, total bilirubin ≥1.5×upper limit of normal;
• Hemoglobin \<100 g/L or need regular blood transfusion;
• Use of drugs that may influence blood glucose within 12 weeks;
• Systemic infection or serious concomitant disease; patients with malignancy or chronic diarrhea;
• Uncontrolled endocrine gland dysfunction;
• Patients with mental or communication disorders;
• Chronic cardiac insufficiency, heart function class III and above;
• Pregnant women, lactating women and women of child bearing age who are not willing to take contraception during the study;
• Subjects who don't cooperate, cannot be followed up or have difficulty in completing the study considered by the investigator.

Sponsors & Collaborators

• Sun Yat-sen University: lead
• The Seventh Affiliated Hospital of Sun Yat-sen University: collaborator
• Guangdong Provincial Hospital of Traditional Chinese Medicine: collaborator
• Guangdong Provincial People's Hospital: collaborator
• The First Affiliated Hospital with Nanjing Medical University: collaborator
• Dongguan People's Hospital: collaborator
• Clifford Hospital: collaborator
• Guangzhou Panyu Central Hospital: collaborator
• Nanfang Hospital, Southern Medical University: collaborator
• Chinese PLA General Hospital: collaborator
• Peking University People's Hospital: collaborator
• Shanghai 10th People's Hospital: collaborator
• Shanghai Changzheng Hospital: collaborator
• Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University: collaborator
• Huizhou Municipal Central Hospital: collaborator

Study Sites (1)

endocrinology department of the first affiliated hospital of Sun Yat-sen University

Guangzhou, Guangdong, 510080, China

Location

Related Publications (1)

• Liu L, Ke W, Li H, Li F, Fan G, Kuang J, Ma J, Zhang X, Ji B, Li S, Du Y, Xue Y, Lyu Z, Gao L, Qu S, Shi Y, Yan L, Deng W, Xu C, Dai P, Xu L, Liu J, Wan X, Wei G, Yu S, Hong S, Zhang P, Huang Z, Cao X, Liao Z, Xiao H, Mu Y, Handelsman Y, Li Y. Intense simplified strategy for newly diagnosed type 2 diabetes in patients with severe hyperglycaemia: multicentre, open label, randomised trial. BMJ. 2024 Oct 15;387:e080122. doi: 10.1136/bmj-2024-080122.

  PMID: 39406449 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Condition Hierarchy (Ancestors)

Diabetes Mellitus; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of Endocrinology and Metabolism Department

Study Record Dates

• First Submitted: June 19, 2017
• First Posted: June 21, 2017
• Study Start: November 1, 2017
• Primary Completion: December 31, 2022
• Study Completion: December 31, 2022
• Last Updated: June 18, 2024

Record last verified: 2024-06

Locations

CN (1)