COMPARATIVE CRITICAL ANALYSIS OF TWO PAPERS

Comparative Critical Analysis of Two Papers

Abstract

Insulin replacement in diabetes often requires prandial intervention to reach hemoglobin A1c (HbA1c) targets. Parallel, randomized, placebo-controlled trial, blocked and stratified by HbA1c level at site, performed from October 2011 to January 2010. Participants, investigators, and personnel conducting the study were masked to treatment assignments. (ClinicalTrials.gov registration number: NCT00765817) The primary outcome was change in HbA1c level. Secondary outcomes included the percentage of participants with HbA1c values of 7.0% or less and 6.5% or less, 7-point self-monitored glucose profiles, body weight, waist circumference, insulin dose, hypoglycemia, and adverse events. Adding twice-daily exenatide injections improved glycemic control without increased hypoglycemia or weight gain in participants with uncontrolled type 2 diabetes who were receiving insulin glargine treatment. Adverse events of exenatide included nausea, diarrhea, vomiting, headache, and constipation.

Comparative Critical Analysis of Two Papers

Introduction

Glycemic control in type 2 diabetes mellitus becomes increasingly challenging with longer duration of disease. Progressive decline in ß-cell function and insulin resistance, combined with increased hepatic glucose output due to glucagon dysregulation, lead to elevations in both fasting and prandial glucose levels. Pharmacologic treatment of diabetes usually involves the sequential addition of oral antihyperglycemic agents according to a target-driven strategy, usually followed by the addition of basal insulin and then prandial insulin (1). This progression, despite increasing numbers and doses of therapeutic agents, is generally associated with persistently elevated hemoglobin A1c (HbA1c) levels and decreased likelihood of achieving glycemic targets with longer duration of diabetes (1-5).

Methods

Study Design

Our 30-week, randomized, double-masked, parallel, placebo-controlled study was conducted in 59 centers in 5 countries (Greece, Israel, Mexico, United Kingdom, and United States) from 29 October 2011 to 4 January 2010. Participants, investigators, and other personnel involved in the conduct of the study were blinded to individual treatment assignments for the duration of the study. The primary objective was to determine whether exenatide injection, 10 µg twice daily, was superior to placebo, as measured by change in HbA1c level, in participants with type 2 diabetes who were receiving insulin glargine with or without metformin or pioglitazone (or both agents). Secondary outcome measures included the percentage of participants with HbA1c levels of 7.0% or less and 6.5% or less; 7-point self-monitored blood glucose (SMBG) profiles; change in body weight, waist circumference, and insulin dose from baseline; and safety (measured by self-reported hypoglycemic events and treatment-emergent adverse events). Exploratory measures included 1,5-anhydroglucitol level at baseline, week 18, and week 30.

Setting and Participants

Participants were at least 18 years of age; had type 2 diabetes; had been receiving insulin glargine at a minimum of 20 U/d without any other insulin, alone or in combination with a stable dose of metformin or pioglitazone (or both agents) for at least 3 months; and had an HbA1c level of 7.1% to 10.5%, body mass index of 45 kg/m2 or less, and stable body weight (less than 5% change over 3 months). Participants were excluded if they had clinically significant hematologic, oncologic, renal, cardiac, hepatic, or gastrointestinal ...