Heterogenous Effects in Diabetes Mellitus Clinical Trials and Implications for Physician Prescriptions

Lead Investigator: Tamar Oostrom, The Ohio State University
Title of Proposal Research: Heterogenous Effects in Diabetes Mellitus Clinical Trials and Implications for Physician Prescriptions
Vivli Data Request: 7759
Funding Source: None
Potential Conflicts of Interest: None

Summary of the Proposed Research:

Medications often have different treatment effects for different individuals. For example, a drug might have higher treatment effects for older patients compared to younger patients, or a drug might work less well for patients with additional comorbidities. This project explores how these different treatment effects translate into physician’s prescribing decisions.

By the design of inclusion and exclusion criteria, and by patient selection, clinical trials enroll a subset of the overall population. However, evidence from clinical trials may be applied to broad patient populations. These populations may be healthier or sicker, younger or older, with more or fewer additional health conditions. What can our evidence from clinical trials tell us about optimal treatment decisions in the real world? We will explore heterogenous treatment effects within clinical trials and explore the implications for physicians’ real-world prescribing decisions in the context of medications for diabetes.

This project will (1) document characteristics of clinical trial participants compared with characteristics of the real-world population of patients that are prescribed diabetes medications. We will also (2) explore which types of patients have larger treatment effects than other groups. We will aggregate results from numerous clinical trials to be able to estimate treatment effects for specific subpopulations. Finally, we will (3) explore how well real-world prescribing decisions correspond to clinical trial treatment effects. For example, if a clinical trial finds that a certain drug works very well for younger patients, are more younger patients prescribed the drug in practice?

Our results will contribute to our understanding of how clinical trial results are interpreted and how clinical trials affect physician practice. We intend to publish our results in high-impact journals and present our work at academic conferences and medical institutions.

Requested Studies:

An Open-label, Randomized, Three-parallel-group Study on Pharmacodynamic Effects of 8-week QD Treatment With Lixisenatide Compared to Liraglutide in Patients With Type 2 Diabetes Not Adequately Controlled With Insulin Glargine With or Without Metformin
Data Contributor: Sanofi
Study ID: NCT01596504
Sponsor ID: PDY12625

A 13-week Multinational, Randomized, Double-Blind, Placebo-Controlled, Dose-Response Trial Assessing the Safety, Tolerability and Efficacy of AVE0010 in Metformin-Treated Subjects With Type 2 Diabetes Mellitus
Data Contributor: Sanofi
Study ID: NCT00299871
Sponsor ID: DRI6012

A Randomized, Placebo-controlled, 2-arm Parallel-group, Multicenter Study With a 24-week Double-blind Treatment Period Assessing the Efficacy and Safety of Lixisenatide in Patients With Type 2 Diabetes Insufficiently Controlled With Insulin Glargine and Metformin
Data Contributor: Sanofi
Study ID: NCT00975286
Sponsor ID: EFC10781

A Randomized, Open-label, Active-controlled, 3-arm Parallel-group, 26-week Study Comparing the Efficacy and Safety of Lixisenatide to That of Insulin Glulisine Once Daily and Insulin Glulisine Three Times Daily in Patients With Type 2 Diabetes Insufficiently Controlled With Insulin Glargine With or Without Metformin
Data Contributor: Sanofi
Study ID: NCT01768559
Sponsor ID: EFC12626

A Randomized, Double-blind, Placebo-controlled, Parallel-group, Multicenter 12-week Study Assessing the Efficacy and Safety of AVE0010 in Patients With Type 2 Diabetes Not Treated With Antidiabetic Agents
Data Contributor: Sanofi
Study ID: NCT00688701
Sponsor ID: EFC6018

A Randomized, Double-Blind, Placebo-Controlled, 2-arm Parallel-group, Multicenter Study With a 24-Week Treatment Period Assessing the Efficacy and Safety of AVE0010 in Patients With Type 2 Diabetes Insufficiently Controlled With Basal Insulin With or Without Sulfonylurea
Data Contributor: Sanofi
Study ID: NCT00866658
Sponsor ID: EFC10887

A Randomized, Open-label, Active-controlled, 2-arm Parallel-group, Multicenter 24-week Study Followed by an Extension Assessing the Efficacy and Safety of AVE0010 Versus Exenatide on Top of Metformin in Patients With Type 2 Diabetes Not Adequately Controlled With Metformin
Data Contributor: Sanofi
Study ID: NCT00707031
Sponsor ID: EFC6019

A Randomized, Double-blind, Placebo-controlled, 2-arm Parallel-group, Multicenter 24-week Study Followed by an Extension Assessing the Efficacy and Safety of AVE0010 on Top of a Sulfonylurea in Patients With Type 2 Diabetes Not Adequately Controlled With Sulfonylurea
Data Contributor: Sanofi
Study ID: NCT00713830
Sponsor ID: EFC6015

A Randomized, Double-blind, Placebo-controlled, Parallel-group, Multicenter, 24-week Study Followed by an Extension Assessing the Efficacy and Safety of AVE0010 in Two Titration Regimens on Top of Metformin in Patients With Type 2 Diabetes Not Adequately Controlled With Metformin
Data Contributor: Sanofi
Study ID: NCT00763451
Sponsor ID: EFC10743

A Randomized, Double-blind, Placebo-controlled, 2-arm Parallel-group, Multicenter Study With a 24-week Main Treatment Period and an Extension Assessing the Efficacy and Safety of AVE0010 in Patients With Type 2 Diabetes Insufficiently Controlled With Basal Insulin
Data Contributor: Sanofi
Study ID: NCT00715624
Sponsor ID: EFC6016

A Randomized, Double-blind, Placebo-controlled, Parallel-group, Multicenter 24-week Study Followed by an Extension Assessing the Efficacy and Safety of AVE0010 on Top of Metformin in Patients With Type 2 Diabetes Not Adequately Controlled With Metformin
Data Contributor: Sanofi
Study ID: NCT00712673
Sponsor ID: EFC6014

A Randomized, Double-blind, Double-dummy, 2-arm Parallel-group, Multicenter 24-week Study Comparing the Efficacy and Safety of AVE0010 to Sitagliptin as add-on to Metformin in Obese Type 2 Diabetic Patients Younger Than 50 and Not Adequately Controlled With Metformin
Data Contributor: Sanofi
Study ID: NCT00976937
Sponsor ID: EFC10780

A Randomized, Double-blind, Placebo-controlled, 2-arm Parallel-group, Multicenter Study With a 24-week Main Treatment Period and an Extension Assessing the Efficacy and Safety of AVE0010 on Top of Pioglitazone in Patients With Type 2 Diabetes Not Adequately Controlled With Pioglitazone
Data Contributor: Sanofi
Study ID: NCT00763815
Sponsor ID: EFC6017

A Randomized, Double-blind, Placebo-controlled, Parallel-group, Multicenter Study to Evaluate Cardiovascular Outcomes During Treatment With Lixisenatide in Type 2 Diabetic Patients After an Acute Coronary Syndrome
Data Contributor: Sanofi
Study ID: NCT01147250
Sponsor ID: EFC11319

A Randomized, Double-blind, Placebo-controlled, 2-arm Parallel-group, Multicenter Study With a 24-week Treatment Period Assessing the Efficacy and Safety of Lixisenatide in Patients With Type 2 Diabetes Insufficiently Controlled With Basal Insulin With or Without Metformin
Data Contributor: Sanofi
Study ID: NCT01632163
Sponsor ID: EFC12382

An Open-label, Multicenter 24-Week And 52-Week Study Assessing The Safety And Tolerability Of Lixisenatide In Monotherapy In Patients With Type 2 Diabetes
Data Contributor: Sanofi
Study ID: NCT01960179
Sponsor ID: SFY13476

An Open-Label, Multicenter 52-Week Study Assessing the Safety and Tolerability of Lixisenatide in Combination With Oral Anti-Diabetic Treatment in Patients With Type 2 Diabetes
Data Contributor: Sanofi
Study ID: NCT01940965
Sponsor ID: LTS12809

Efficacy and Safety of Lixisenatide in Patients With Type 2 Diabetes Mellitus Insufficiently Controlled by Metformin (With or Without Sulfonylurea): a Multicenter, Randomized, Double-blind, Parallel-group, Placebo-controlled Study With 24-week Treatment Period
Data Contributor: Sanofi
Study ID: NCT01169779
Sponsor ID: EFC11321

A 52 Week Randomized, Double-Blind, Multicenter, Mechanistic Study With a 24 Week Open-Label Follow-Up to Evaluate the Effect of AVANDIA TM on Bone in Postmenopausal Women With Type 2 Diabetes Mellitus
Data Contributor: GSK
Study ID: NCT00679939
Sponsor ID: AVD111179

AVANDIA CV Outcomes Study: Thiazolidinedione Intervention With Vitamin D Evaluation (TIDE) A Multicenter Randomized Double-Blind Placebo-Controlled Trial of a Thiazolidinedione or Placebo and of Vitamin D or Placebo In People With Type 2 Diabetes at Risk For Cardiovascular Disease
Data Contributor: GSK
Study ID: NCT00879970
Sponsor ID: 111960

A Single-Center, Non-Randomized, Open-Label, Comparative Study to Assess the Utility of Novel Technologies and Biomarkers as Methods for Measuring Human Pharmacodynamic Response to 8 Weeks of Administration of Rosiglitazone Maleate 4mg BID in Healthy Normal or Overweight Controls, Healthy Obese Subjects and Subjects With Type 2 Diabetes Mellitus (T2DM)
Data Contributor: GSK
Study ID: NCT00551564
Sponsor ID: DIX110434

A Randomized, Double-Blind Study to Compare the Durability of Glucose Lowering and Preservation of Pancreatic Beta-Cell Function of Rosiglitazone Monotherapy Compared to Metformin or Glyburide/Glibenclamide in Patients With Drug-Naive, Recently Diagnosed Type 2 Diabetes Mellitus
Data Contributor: GSK
Study ID: NCT00279045
Sponsor ID: 49653/048

A Study to Evaluate the Efficacy of Rosiglitazone (BRL-049653) on Reduction of Microalbuminuria in Subjects With Type 2 Diabetes Mellitus
Data Contributor: GSK
Study ID: NCT00500955
Sponsor ID: BRL-49653/137

A Long Term, Open Label, Randomised Study in Patients With Type 2 Diabetes, Comparing the Combination of Rosiglitazone and Either Metformin or Sulfonylurea With Metformin Plus Sulfonylurea on Cardiovascular Endpoints and Glycaemia
Data Contributor: GSK
Study ID: NCT00379769
Sponsor ID: BRL-049653/231

A Multicenter, Randomized, Double-Blind, Parallel-Group, Placebo-Control, Clinical Evaluation of Rosiglitazone in Combination with Glimepiride Compared to Glimepiride Plus Placebo for 24 Weeks in Subjects with Type 2 Diabetes Mellitus Who are Inadequately Controlled on Non-TZD Oral Monotherapy
Data Contributor: GSK
Study ID: 49653/325
Sponsor ID: 49653/325

Effect of Rosiglitazone and Placebo on Carotid Intima Media Thickness in Patients With Insulin Resistance Syndrome and/or Type 2 Diabetes
Data Contributor: GSK
Study ID: NCT00306644
Sponsor ID: 49653/334