Type 2 Diabetes in Practice
An Expert Commentary With
Clifford J. Bailey, PhD
A Clinical Context Report
Clinical Context: Type 2 Diabetes in Practice
Expert Commentary
Jointly Sponsored by:
and
Clinical Context: Type 2 Diabetes in Practice
Expert Commentary
This activity is supported by an independent
educational grant from
Boehringer Ingelheim Pharmaceuticals, Inc.
which was made possible, in part, through a
collaboration with Eli Lilly and Company.
Type 2 Diabetes in Practice
Clinical Context Series
The goal of this series is to provide up-todate information and multiple perspectives
on the pathogenesis, patient identification,
symptoms, risk factors, and current and
emerging treatments and best practices in
the management of type 2 diabetes.
Type 2 Diabetes in Practice
Clinical Context Series
Target Audience
Endocrinologists, cardiologists, diabetes
educators, primary care physicians,
nurses, nurse practitioners, physician
assistants, pharmacists, and other
healthcare professionals involved in the
care of patients with type 2 diabetes.
Activity Learning Objective
CME Information: Physicians

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
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Discussant
Clifford J. Bailey, PhD
Professor of Clinical Medicine
Aston University
Department of Life & Health Sciences
Birmingham, UK
Disclosure Information
Clifford J. Bailey, PhD,
disclosed the following relevant financial
relationships:
Board Member/Advisory Panel: Boehringer Ingelheim
Pharmaceuticals; Bristol-Myers Squibb;
GlaxoSmithKline; Merck Sharp & Dohme Limited;
Novo Nordisk; Roche Pharmaceuticals.
Research Support: sanofi-aventis.
Disclosure Information
Dori F. Zaleznik, MD, Associate Clinical Professor of
Medicine, Harvard Medical School, Boston; Crystal
Phend; and Dorothy Caputo, MA, RN, BC-ADM, CDE,
Nurse Planner, have disclosed that they have no relevant
financial relationships or conflicts of interest with commercial
interests related directly or indirectly to this educational
activity.
The staffs of Projects In Knowledge and MedPage Today
have no relevant financial relationships or conflicts of interest
with commercial interests related directly or indirectly to this
educational activity.
Type 2 Diabetes Global Prevalence
•
More than doubled worldwide from 1980
to 2008
— From 8.3% to 9.8% among adult men
— From 7.5% to 9.2% among adult women
Source: Danaei G, et al Lancet 2011; 378: 31-40.
Microvascular Risk Reduction With Better
Glycemic Control
•
United Kingdom Prospective Diabetes Study
(UKPDS)
— Each percentage point decrease in hemoglobin
A1c reduced microvascular complication risk by
35%
•
Diabetes Control and Complications Trial (DCCT)
— A two-percentage point reduction in hemoglobin
A1c cut occurrence of microvascular
complications by 39% to 76%
Sources:
UKPDS Group Lancet 1998; 352: 837-853.
DCCT Research Group N Engl J Med 1993; 329: 977-986.
Recent Trials of More Intensive Glucose
Control
•
Mean diabetes duration at baseline:
— Action to Control Cardiovascular Risk in Diabetes
(ACCORD) – 10 years
— Action in Diabetes and Vascular Disease:
Preterax and Diamicron Modified Release
Controlled Evaluation (ADVANCE) – 8 years
— Veterans Affairs Diabetes Trial (VADT) – 11.5 years
Sources:
ACCORD Study Group N Engl J Med 2008; 358: 2545-2559.
ADVANCE Collaborative Group N Engl J Med 2008; 358: 2560-2572.
Duckworth W, et al N Engl J Med 2009; 360: 129-139.
Early Start Matters
•
UKPDS – Micro- and macrovascular benefits
from more intensive glucose management in
newly diagnosed type 2 diabetes
•
VADT – No micro- or macrovascular benefits
from more intensive glucose management in
advanced type 2 diabetes
Sources:
Holman RR, et al N Engl J Med 2008; 359: 1577-1589.
Holman RR, et al N Engl J Med 2008; 359: 1565-1576.
Duckworth W, et al N Engl J Med 2009; 360: 129-139.
Once-Weekly Exenatide (Bydureon)
•
Extended release formulation of twice-daily
exenatide (Byetta)
•
FDA approval declined in October 2010
•
European Medicines Agency granted
approval in June 2011
Dipeptidyl Peptidase-4 (DPP-4) Inhibitors
•
Sitagliptin (Januvia)
•
Saxagliptin (Onglyza)
•
Linagliptin (Tradjenta) – Approved by FDA in
May 2011
G-Protein-Coupled Receptor Stimulation
•
Raises GLP-1 levels indirectly
•
Oral delivery
•
Early phase research
Summary
At the end of this activity, participants should understand:

Type 2 diabetes prevalence is on the rise,
bringing with it a pending tide of cardiovascular
complications

Deterioration of beta-cell function contributes to
progression of type 2 diabetes, which often is
marked by worsening insulin resistance as well.
Both processes are typically well under way by
the time of diagnosis
Summary

Better glycemic control is linked to reduced risk
of microvascular disease and, over the long term,
lower risk of macrovascular disease as well

Early intervention is key to these effects, as the
ACCORD, VADT, and other trials have shown that
more intensive efforts are largely ineffective later
in the course of type 2 diabetes

Animal studies have suggested that very early
use of incretin drugs can delay beta-cell decline
Summary

Incretin mimetics new to the clinic and on the
horizon include the DPP-4 inhibitor linagliptin,
which was approved by the FDA earlier this year,
and a once-weekly formulation of the GLP-1
receptor agonist drug exenatide recently
approved in Europe that is under review in the
U.S.

A novel class of oral drugs that raise GLP-1
indirectly through G-protein-coupled receptor
stimulation is in early stage development