Measurement of Alanine Aminotransaminase (ALT) Following Initiation of Antidiabetic Agents in Patients With Type 2 Diabetes in a Real-world Clinical Setting: a Retrospective Cohort Study

Study Overview
=================
Brief Summary
-----------------
The primary objective of this study is to investigate the change in Alanine Aminotransaminase (ALT) in patients with Type 2 Diabetes Mellitus (T2DM) initiating Sodium Glucose Cotransporter 2 (SGLT2) inhibitors, liraglutide, or sitagliptin, compared to a control group of patients who did not initiate a new antihyperglycemic therapy. The hypothesis is that patients using Sodium Glucose Cotransporter 2 inhibitors (SGLT2i) will achieve a greater reduction in ALT compared to the control group.

Detailed Description
-----------------
Non-alcoholic fatty liver disease (NAFLD) is very commonly associated with type 2 diabetes mellitus (T2DM) 1. Alanine aminotransferase (ALT) is a common biomarker used to predict levels of NAFLD. The only class of antidiabetic agents thought to be protective of NAFLD are thiazolidinedione's. Few studies have investigated the effect of other antidiabetic agents on bio markers of fatty liver disease 2. A recent pooled analysis of randomized controlled trials that compared canagliflozin to either placebo or sitagliptin showed significant reductions in ALT in the canagliflozin cohorts, which were fully explained by HbA1c and body weight reductions 3. As well, a study that compared ALT change in patients initiating liraglutide found significant reductions in ALT, which was strongly correlated to reduction in body weight 4. However, the effect of different antidiabetic agents on bio markers of fatty liver disease is not well characterized. The primary objective of this study is to investigate the change in ALT in patients with T2DM initiating SGLT2 inhibitors, liraglutide, or sitagliptin, compared to a control group of patients who did not initiate a new antihyperglycemic therapy. The hypothesis is that patients using SGLT2i will achieve a greater reduction in ALT compared to the control group.

Official Title
-----------------
Measurement of Alanine Aminotransaminase (ALT) Following Initiation of Antidiabetic Agents in Patients With Type 2 Diabetes in a Real-world Clinical Setting: a Retrospective Cohort Study

Conditions
-----------------
Fatty Liver, T2DM (Type 2 Diabetes Mellitus), NAFLD

Intervention / Treatment
-----------------
* Other: Non-interventional


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Diagnosis of T2DM based upon historical clinical diagnosis Patients who initiated canagliflozin, dapagliflozin, liraglutide or sitagliptin by an LMC physician between January 2011 and December 2015, or patients who did not initiate a new diabetes therapy between June 2014 and June 2015. Exclusion Criteria: Diagnosis of type 1 diabetes Patients who switched to one of the study treatments from another medication of the same medication class

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

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

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

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

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| SGLT2<br>Patients initiating SGLT2 inhibitors | Other: Non-interventional<br> <br> |
| Liraglutide<br>Patients initiation liraglutide | Other: Non-interventional<br> <br> |
| Sitagliptin<br>Patients initiating sitagliptin | Other: Non-interventional<br> <br> |
| Control Group<br>Patients who did not initiate any new anti-hyperglycemic treatment | Other: Non-interventional<br> <br> |

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in ALT in patients with T2DM initiating SGLT2 inhibitors, Liraglutide or Sitagliptin compared to control | Change in ALT in patients with T2DM initiating SGLT2 inhibitors, Liraglutide or Sitagliptin compared to control | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Hemoglobin A1c from baseline to follow-up | Change in HbA1c from baseline to follow-up | 1 year | 
| Change in Fasting Plasma Glucose from baseline to follow-up | Change in Fasting Plasma Glucose from baseline to follow-up | 1 year | 
| Change in body weight from baseline to follow-up | Change in body weight from baseline to follow-up | 1 year | 
| Change in Body Mass Index (BMI) from baseline to follow-up | Change in BMI from baseline to follow-up | 1 year | 
| Change in Waist Circumference (WC) from baseline to follow-up | Change in WC from baseline to follow-up | 1 year | 
| Change in triglycerides from baseline to follow-up | Change in triglycerides from baseline to follow-up | 1 year |