- WHAT IS NEW ?
Sitagen 50mg,100mg / Sitagen-M 50/500mg
What is New in This Presentation
•Oral Anti Diabetics Agent
•Management of Type 2 Diabetes
•ADA Guidelines 2014
•Strategies for Antidiabetic Treatment
•Master Decision Path For Type 2 Diabetes Glycemic Control
•Incretins – What are they?
•What Is DPP-4?
•Summary of Sitagliptin
•In Pakistan 12.9 Million people with diabetes( 10% of total
•Diagnosed: 9.4 million
•Pre diabetes: 38 million people
Type 1 diabetes
Type 2 diabetes
Choice of agents in current use
c) Thiazolidindiones (TZDs)
e) α- Glucosidase inhibitors
All Current Treatments for Type 2 Diabetes
Insulin Meglitinides Metformin Acarbose Thiazolidi-
Hypoglycemia √ √ √
Weigh gain √ √ √ √
GI side effects √ √
Lactic acidosis √
√ √ √
Fluid Retention √
Tripathi.2005 5th edition
Pharmacology & Therapeutics.2010:125;328–3615
No Single Class of Oral Antihyperglycemic
Monotherapy Targets All Key Pathophysiologies
s3 SUs4,5 TZDs6,7
1. Glyset [package insert]. New York, NY: Pfizer Inc; 2004. 2. Precose [package insert]. West Haven, Conn: Bayer; 2004.
3. Prandin [package insert]. Princeton, NJ: Novo Nordisk; 2006. 4. Diabeta [package insert]. Bridgewater, NJ: Sanofi-Aventis; 2007.
5. Glucotrol [package insert]. New York, NY: Pfizer Inc; 2006. 6. Actos [package insert]. Lincolnshire, Ill: Takeda Pharmaceuticals; 2004.
7. Avandia [package insert]. Research Triangle Park, NC: GlaxoSmithKline; 2005.
8. Glucophage [package insert]. Princeton, NJ: Bristol-Myers Squibb; 2004.
Basic Steps in the Management of Type 2 Diabetes
Master Decision Path
Type 2 Diabetes Glycemic Control
Medical Nutrition Therapy
& Activity Plan
Oral combination treatment 2 drugs
If target not reached after maximum
dose for 4 - 8 weeks - - start oral agent
Insulin Therapy Oral Agent(s) + Insulin
Oral Combination Rx 3 drugs
If target not reached after maximum
doses for 4 - 8 weeks -- start insulin
FPG < 200
Casual < 250
FPG > 350
Casual > 400
FPG > 300-350
Casual > 350-400
with severe symptom
Incretins – What are they?
Hormones produced by the gastrointestinal tract in response
to incoming nutrients, and have important actions
that contribute to glucose homeostasis.
Gastric inhibitory polypeptide (GIP)
Glucagon-like peptide-1 (GLP-1).
INCRETIN= INtestinal+seCRETion of INsulin
What Is DPP-4?
• A serine protease widely distributed throughout the
• Cleaves N-terminal amino acids of a number of
active peptides, including the incretins GLP-1 and
gastric inhibitory peptide (GIP), resulting in
• Its effects on GLP-1 and GIP have been shown to affect
• Inactivates GLP-1 >50% in ~1 to 2 minutes
Ahrën B. Curr Enzyme Inhib. 2005;1:65-73.
DPP4 inhibitors such as Sitagliptin Inhibit
the degradation of incretins and thus
Prolong the half life of Endogenous Incretins
Action of Sitagliptin is Glucose-Dependent
And Hence Hypoglycemia is Less Common
• Reduces hemoglobin A1c (HbA1c), fasting and postprandial
glucose by glucose dependant stimulation of insulin secretion
and inhibition of glucagon secretion.
• Sitagliptin is selective inhibitor of the enzyme DPP-4.
• Delays gastric emptying and reduce appetite.
Mechanism of action (MOA)
Bioavailability of Sitagliptin is approximately 87% .
Half life is between 8-14 hours.
It is 38% bound to plasma proteins.
Elimination is mainly through urine.
a) reducing both fasting and postprandial glucose
b) clinically meaningful reductions in glycosylated
hemoglobin (HbA1c) levels in type 2 diabetic patients.
• Monotherapy with Sitagliptin 100 mg daily decreases mean
HbA1c by 0.6-0.98%.
Pharmacology & Therapeutics.2010;25:328-361
• In very well controlled randomized clinical trials Sitagliptin
(100 mg) treatment significantly improved glycemic control
• Improved Homeostasis model assessment of β cell and
• Sitagliptin (100 mg) monotherapy for 18 weeks significantly
improved glycemic control by reducing HbA1c, fasting and
postprandial glucose in Indian type 2 diabetic (T2D) patients .
Efficacy & Safety of Sitagliptin in Indian T2D patients
• Sitagliptin was well tolerated and no hypoglycemia
Diabetes Research and Clinical Practice.2009;83:106-116
Sitagliptin and Blood Pressure
J Clin Pharmacol. 2008 May;48(5):592
• Sitagliptin treatment significantly reduced blood pressure
and was well tolerated in type 2 diabetic and non-diabetic
Sitagliptin and Inflammatory Markers
• Sitagliptin (100 mg) treatment for 3 months decreased
inflammatory markers C-reactive protein (CRP), Interleukin-6
(IL-6), Myeloperoxidase (MPO), Monocyte chemotactic
protein-1 (MCP-1) in type 2 diabetic patients with
• Changes in markers levels correlated with the improvement
of glycemic control as shown by Hb A1c.
Journal of Clinical Lipidology.2008;2(5S):S137-138
Sitagliptin Vs Voglibose
Diabetes Obese Metab.2010;12(7):613-22
• In comparative, randomized clinical trial, once daily
Sitagliptin monotherapy showed greater efficacy and
better tolerability than thrice daily Voglibose (alpha-
glucosidase inhibitor) over 12 week in type 2 diabetes patients.
Significantly reduced HbA1c
Significant lowered side effects
Significantly reduced fasting and postprandial plasma glucose
• In clinical trials, Sitagliptin demonstrated an overall incidence
of side effects comparable to placebo.
• The incidence of Hypoglycemia with Sitagliptin monotherapy
was not Significantly different than placebo.
• Upper respiratory tract infection, stuffy or running nose, sore
throat, headache and diarrhea was reported with Sitagliptin
• No significant change in body weight was reported.
• The recommended dose of Sitagliptin is 100 mg once
daily. It may be taken with or without food.
•Maximum Dose 200mg/day
•If administered with sulfonylurea: a reduced dose of
sulfonylurea may be required.
• Sitagliptin plasma concentration may be increased modest
(approximately 68%) with Cyclosporine which is not
expected to be clinically important.
• Digoxin plasma levels may be increased slightly
(approximately18%), no dosage adjustment is recommended.
• Care should be taken with drugs that can potentially lower
blood sugar, such as: Probencid, NSAIDs, Aspirin, Sulfa
drugs, MAO inhibitors or Beta blockers.
• Sitagliptin is a pregnancy category B drug.
• Sitagliptin is contraindicated in diabetic ketoacidosis.
In severe renal function impairment (Ccr less than 30
mL/min) dose should be reduced to 25 mg once daily.
In moderate renal function impairment (Ccr 30 to less
than 50mL/min) dose should be reduced to 50mg once daily.
• Dosage adjustments are needed in patients with moderate
or severe renal function impairment.
• In October 2006, the U.S. Food and Drug Administration
(FDA) approved Sitagliptin as monotherapy and as add-on
therapy to either of two other types of oral diabetes
• In April, 2007 FDA approved the combination product of
Sitagliptin and Metformin for type 2 diabetes.
• In March, 2007 it was approved in European Union.
• Sitagliptin is currently approved in 70 Countries.