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 (ALT)

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.

Study Overview

• Status: Completed
• Conditions: Fatty Liver; NAFLD; T2DM (Type 2 Diabetes Mellitus)
• Intervention / Treatment: Other: Non-interventional

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.

• Study Type: Observational
• Enrollment (Actual): 4000

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Brampton, Ontario, Canada, L6S 0C9
      • LMC Brampton

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

This study will include patients with T2DM who are patients at LMC Diabetes & Endocrinology. Patients will be included in the treatment cohorts if they initiated canagliflozin, dapagliflozin, liraglutide or sitagliptin, between January 2011 and December 2015, and did not discontinue the treatment prior to 6 weeks of being on the medication. The control group will include patients with T2DM who are patients at LMC Diabetes & Endocrinology, and who did not initiate any new diabetes treatment between June 2014 and June 2015.

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
SGLT2; Patients initiating SGLT2 inhibitors	Other: Non-interventional
Liraglutide; Patients initiation liraglutide	Other: Non-interventional
Sitagliptin; Patients initiating sitagliptin	Other: Non-interventional
Control Group; Patients who did not initiate any new anti-hyperglycemic treatment	Other: Non-interventional

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

Collaborators and Investigators

• Sponsor: LMC Diabetes & Endocrinology Ltd.

Publications and helpful links

General Publications

• Bajaj HS, Brown RE, Bhullar L, Sohi N, Kalra S, Aronson R. SGLT2 inhibitors and incretin agents: Associations with alanine aminotransferase activity in type 2 diabetes. Diabetes Metab. 2018 Dec;44(6):493-499. doi: 10.1016/j.diabet.2018.08.001. Epub 2018 Aug 24.

Study record dates

Study Major Dates

• Study Start (Actual): January 1, 2017
• Primary Completion (Actual): June 1, 2017
• Study Completion (Actual): June 1, 2017

Study Registration Dates

• First Submitted: July 20, 2017
• First Submitted That Met QC Criteria: July 27, 2017
• First Posted (Actual): July 28, 2017

Study Record Updates

• Last Update Posted (Actual): July 28, 2017
• Last Update Submitted That Met QC Criteria: July 27, 2017
• Last Verified: July 1, 2017

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Liver Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Fatty Liver
• Other Study ID Numbers: ALT

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No