dpp - 4 inhibitors are a newer class of drugs for management of type 2 diabetes mellitus.

1. DPP – 4 Inhibitors :
Mechanism of Action& Role
in DM - 2 Management
Dr. Arun Sharma

2. BRIEF INTRODUCTION : T2DM
 Prevalent chronic healthcare disease with a significant
global disease burden.
 Achieving specific glycemic goals substantially
reduces morbidity & have made the effective treatment
of hyperglycemia a top priority.
 Intensive glycemic control has a powerful beneficial
effect on diabetes-specific complications.
 Development of new classes of blood glucose-
lowering medications has increased the number of
treatment options.

3. DPP-4 Inhibitors : A Novel
approach in T2DM Management
 DPP 4 inhibitors inhibit the breakdown of Incretin peptide hormones
and increase the Incretin effect in patients with type 2 DM.
 Their development was based on observations that factors
secreted from gut participated in regulation of pancreatic endocrine
secretion.These gut factors were termed “Incretins”.
 Two Incretin peptide hormones have been identified in
humans,namely Glucose dependent insulin releasing polypeptide
(GIP) and Glucagon like peptide -1 (GLP-1)
 Incretins are rapidly inactivated by dipeptidyl peptidase-4 (DPP-4).
The DPP-4 inhibitors prolong the action of endogenous incretins,
enhancing the first-phase insulin response.

4. Incretins and glycemic
control
Adapted from 7. Drucker DJ. Cell Metab. 2006;3:153–165. 8. Miller S, St Onge EL. Ann Pharmacother 2006;40:1336-1343.
Active
GLP-1 and GIP
Release of
incretin gut
hormones
Pancreas
Blood
glucose
control
GI tract
 Glucagon
from alpha cells
(GLP-1)
Glucose
dependent
Alpha cells
Increased insulin
and decreased
glucagon
reduce
hepatic
glucose output
Glucose dependent
 Insulin
from beta cells
(GLP-1 and GIP)
Beta cells
Insulin
increases
peripheral
glucose
uptake
Ingestion
of food
DPP-4
enzyme
rapidly
degrad
es
incretins

5. Functions of Incretins

6. DPP – 4 Inhibitors in Clinical
Practice
A list of available and expected gliptins :
 Sitagliptin (Merck Sharp and Dohme Corp, approved as Januvia by US FDA in year 2006)
 Vidagliptin (Novartis, approved as Galvus by EU in year 2007)
 Saxagliptin (Bristol-Myers Squibb, approved as Onglyza by US FDA in 2010)
 Linagliptin (Boerhinger Ingelheim, approved as Tradjenta by US FDA in year 2011)
 Alogliptin (developed by Takeda Pharmaceutical Company Limited, approved for use in Japan)
 Dutogliptin (being developed by Phenomix Corporation)
 Gemigliptin (being developed by LG Life Sciences)
 Linagliptin has recently been approved in India.
 In clinical trials,most of these drugs have been shown to reduce HbA1c significantly when used
either as monotherapy or in combination with Metformin, Sulphonylureas or a combination of
both.
 They are also associated with lower rates of hypoglycemia and have also been shown to be
weight neutral.

7. Comparative Pharmacokinetic
Profile

8. Advantages of Using DPP – 4
Inhibitors
 As Monotherapy : Shown to be equally efficacious as compared to other
antidiabetic agents with added advantage of lesser incidence of
hypoglycemia and being weight neutral.
 As Initiation Therapy : Can be safely coupled with Metformin as an Inititaion
therapy as per the latest guidelines (ADA guideline)
 Insulin dose can be reduced if given with gliptins as a combination therapy.
 No significant drug – drug interaction with other drugs so can be given
safely with anti-hypertensives,anti-hyperlipidemics & antibiotics.
 Cardiac friendly profile :Studies suggest that DPP-4 inhibitors have a
cardiovascular friendly profile. Preclinical studies have suggested
endothelial benefit, anti-atherosclerotic effects and blood pressure lowering
effects.

9. Advantages of Using DPP – 4
Inhibitors : Continued
 Safe in Hepatic Inefficiency : For patients with hepatic
insufficiency, except for vildagliptin, no dose adjustment
is necessary for gliptins.
 Safe in Renal Insufficiency :Linagliptin is safe in renal
insufficiency.Other gliptins can be used safely with dose
adjustments.
 Well Tolerated in most people with not much significant
adverse event profile.

10. Conclusion
 Need for newer medications in T2DM
Management.
 DPP - 4 Inhibitors offer a promising treatment
modality in T2DM.
 Need for continued research to evaluate long
term safety and adverse event profile in
patients.

11. References
 Indian Journal Of Endocrinology &
Metabolism 2011 Oct-Dec; 15(4): 298–308.
 www.Diabetesincontrol.com
 www.diabetesjournals.org
 www.qjmed.oxfordjournals.org

12. THANK YOU
Dr. Arun Sharma
M.B.B.S.