The Effect of Glimepiride Compared With Sitagliptin as an add-on Therapy to Metformin in Severe Insulin Deficiency Diabetes

Study Overview
=================
Brief Summary
-----------------
The purpose of the trial is to verify the effectiveness and safety of glimepiride compared with sitagliptin as an add-on therapy to metformin in severe insulin deficiency diabetes.

Detailed Description
-----------------
This clinical trial is a multi-centre, prospective, intervention, randomized-controlled clinical trial, and uses a superiority test to determine whether the experimental group is superior to the control group in terms of main efficacy endpoints.

Official Title
-----------------
The Effect of Glimepiride Compared With Sitagliptin as an add-on Therapy to Metformin in Severe Insulin Deficiency Diabetes

Conditions
-----------------
Diabetes Mellitus, Type 2, Severe Insulin Deficient Diabetes

Intervention / Treatment
-----------------
* Drug: Glimepiride
* Drug: Sitagliptin


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: According to the World Health Organization (the WHO) 1999 criteria for the diagnosis of type 2 diabetes; the subtype was allocated to severe insulin deficiency diabetes (SIDD) at diagnosis using data-driven diabetes clusters APP. Men and women aged ≥ 18 years and ≤ 75 years; Diagnosed as severe insulin deficiency diabetes by the cluster classifier of Peking University People's Hospital at the initial stage of the disease course; Metformin monotherapy with dosage ≥1500 mg/day for at least 8 weeks; Diabetes duration less than 5 years; The HbA1c value of the central laboratory before randomization: 7.0% ≤ HbA1c <10.5% estimated estimated glomerular filtration rate (eGFR)>=60 ml/min1.73m2, alanine aminotransferase(ALT)<120U/L ; If other drugs are used during the course of the disease, these drugs should be withdrawn for more than 8 weeks; Without acute diabetic complications at present. Exclusion Criteria: Type 1 diabetes or other special types of diabetes mellitus; glutamic acid decarboxylase antibody (GADA) positive, the subtype was allocated to other subtypes at diagnosis using data-driven diabetes clusters APP. Pregnancy or have a pregnancy plan within a year; Lactation or have a lactation plan within a year; Renal insufficiency, eGFR<60; transaminase elevated, ALT>= 120U/L; unstable coronary heart disease. Recurrent spontaneous diabetic ketosis or uncorrected acute diabetic complications; Participated in other clinical trials within 8 weeks before randomization; Unable to complete the study follow-up for 6 months; Have situations such as operation and need to change to insulin therapy in 6 months. Use concomitant medication such as glucocorticoids which can affect blood sugar. The investigator judged that it is not suitable to participate in this clinical trial.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Glimepiride<br>All participants have background therapy of metformin 1500mg-2000mg, glimepiride1-4mg were added in the patients randomised to this arm considering the baseline HbA1c of the participants. | Drug: Glimepiride<br>* Initiate glimepiride 1-4mg once daily as an add-on therapy to metformin and adjust the glimepiride dosage to 1-6 mg once daily in the first 12 weeks according to the diabetes management guideline recommended by the Chinese Diabetes Society.<br>* Other names: SU group (sulphonylurea group);|
| Active Comparator: Sitagliptin<br>All participants have background therapy of metformin 1500mg-2000mg, Sitagliptin 100mg were added in the patients randomised to this arm regardless of the baseline HbA1c level in this arm. | Drug: Sitagliptin<br>* Add sitagliptin 100mg once daily in all patients randomized to this arm.<br>* Other names: DPPIVi Group (dipeptidyl peptidase IV inhibitor group);|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Reduction of hemoglobin A1c from baseline at the end of the trial. | The Least squre mean of the decline of hemoglobin A1c from baseline to the end of the trial | 26 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Hemoglobin A1c on-target rate | the percentage of A1c<7.0% or A1c<6.5% | 26 weeks | 
| The difference of self measure blood glucose (SMBG) at every month | The mean of 4-point SMBG for every four weeks | for 26 weeks | 
| The incidence rate of hypoglycemia | Any measurement of blood glucose<3.9mmol/L or symptoms related to hypoglycemia | for 26 weeks | 
| The level of weight gain | The difference between body weights at the beginning and end of the trial | for 26 weeks |