DPP4i:

SITAGLIPTIN
Doc. No: ID-DSM-00035 Exp.Date : Feb 2023

A PRODUCT PRESENTATION

PRODUCT INDICATIONS EFFICACY SAFETY OTHERS HIGHLIGHTS

 American Diabetic Association, 2020
Doc. No: ID-DSM-00035 Exp.Date : Feb 2023

PRODUCT INDICATIONS EFFICACY SAFETY OTHERS HIGHLIGHTS

 SITAGLIPTIN

1 2 3
HIGHLY STIMULATES
TREATMENT INSULIN
SELECTIVE
FOR RELEASE AND
INHIBITOR OF
TYPE 2 SUPPRESSES
DIPEPTIDYL
DIABETES HEPATIC
PEPTIDASE 4
(DPP-4) GLUCOSE
ENZYME OUTPUT

Reference: Local Product Circular. Data on file, MSD Indonesia.

PRODUCT INDICATIONS EFFICACY SAFETY OTHERS HIGHLIGHTS

 SITAGLIPTIN
Doc. No: ID-DSM-00035 Exp.Date : Feb 2023

INITIAL FOR PATIENTS IN COMBINATION

THERAPY NOT WITH
AS ADJUNCT TO DIET CONTROLLED ON SULFONYLUREAS
AND EXERCISE METFORMIN PPAR γ AGONIST
INSULIN

Reference: Local Product Circular. Data on file, MSD Indonesia.

PRODUCT INDICATIONS EFFICACY SAFETY OTHERS HIGHLIGHTS

 SITAGLIPTIN
Doc. No: ID-DSM-00035 Exp.Date : Feb 2023

EFFICACY AND SAFETY DATA

PRODUCT INDICATIONS EFFICACY SAFETY OTHERS HIGHLIGHTS

 POWERFUL HBA1C REDUCTIONS,
AS MUCH AS –3.6% IN A HIGH-BASELINE
HBA1C SUBGROUP
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Reference: Engel, SS et al. Endocr.Pract.2013; 19:751-757

PRODUCT INDICATIONS EFFICACY SAFETY OTHERS HIGHLIGHTS

 SUSTAINED EFFICACY OVER
A 5-YEAR PERIOD
Doc. No: ID-DSM-00035 Exp.Date : Feb 2023

Reference: De Rosa G et al. Pharmacol Res 2015;100:127-134.

PRODUCT INDICATIONS EFFICACY SAFETY OTHERS HIGHLIGHTS

 EFFICACY ACROSS ALL STAGES OF
RENAL IMPAIRMENT IN
ACTIVE CONTROLLED STUDIES
*
Doc. No: ID-DSM-00035 Exp.Date : Feb 2023

p= NS for all comparisons

*Sitagliptin 25 mg is not marketed in Indonesia

References: 1. Nauck M, et al. Diab Obes Metab 2007;9:194-205. 2. Ferreira J, et al. Diabetes Care. 2013;36:1067– 1073. 3. Ferreira JC, et al.
Am J Kidney Dis. 2013;61:579–587

PRODUCT INDICATIONS EFFICACY SAFETY OTHERS HIGHLIGHTS

 GREATER HbA1c REDUCTIONS AMONG
EAST ASIAN PATIENTS
Doc. No: ID-DSM-00035 Exp.Date : Feb 2023

References: 1. Davis TME, et al. Diabetes Obes Metab. 2018;20:1427-1434. 2. Conceicao J, et al. Glycemic Efficacy of Sitagliptin in East Asian
Populations: A Pooled Analysis. Poster presented at: ADA 2019; June 8–12; 2019 San Francisco, California.
Poster 1188-P.

PRODUCT INDICATIONS EFFICACY SAFETY OTHERS HIGHLIGHTS

 CompoSIT
COMPARATIVE TRIALS WITH SITAGLIPTIN

CompoSIT R CompoSIT I CompoSIT M

SITAGLIPIN SITAGLIPIN resulted in SITAGLIPIN addition

With maximization
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Provides superior A1c Greater reduction in result in:

reductions A1c and FPG
Gets more patients to More patients to A1c Greater HbA1c
A1c < 7% <7.0% reduction
Is associated with less Lower daily insulin More patients with
trearmenr related AEs dose HbA1c goal attainment

Comparison of Sitagliptin with Comparison of Sitagliptin vs Comparison of up-titration of

Dapagliflozin in mild renal placebo during initiation & metformin plus sitagliptin vs
impairment titration of insulin glargine metformin up-titration alone

References: 1. Scott R, et al. Diabetes Obes Metab. 2018 Dec;20(12):2876-2884. 2. Roussel R, et al. Diabetes Obes Metab 2018;1-10. 3. Frias J,
et al. Diabetes Obes Metab 2019;21:1128–1135.

PRODUCT INDICATIONS EFFICACY SAFETY OTHERS HIGHLIGHTS

 Proven Safety Profile for T2DM Patients with
History of Cardiovascular Disease
Sitagliptin met the primary end point
No increased risk in the composite CV end point of time to the first confirmed event of:
CV – related death
Doc. No: ID-DSM-00035 Exp.Date : Feb 2023

Non-fatal
Non-fatal
Myocardial
stroke
Infarction (MI)

Unstable angina requiring hospitalization

Reference: Green JB et al. NEJM 2015;373(3):232-242.

PRODUCT INDICATIONS EFFICACY SAFETY OTHERS HIGHLIGHTS

 Proven Safety Profile for T2DM Patients with
History of Cardiovascular Disease
No heterogeneity for the effect was observed in subgroup analyses across 21
factors (P>0.10 for all interactions)

Patients with previous Patients with concomitant

Doc. No: ID-DSM-00035 Exp.Date : Feb 2023

heart failure2 insulin therapy1

Patients with renal

Patients with high HbA1c level1
impairment3 (mean HbA1c >7.2%)
(eGFR <60 mL/min/1.73 m2)

Elderly Patients4 Moslem patients who actively

(mean age >65.5 years) participate to fast in Ramadan
month 5,6,7
References: 1. McGuire D, et al. JAMA Cardiol. 2016;1(2):126-135. 2. Cornel J, et al. Diabetes Care 2016;39:2304–2310. 3. Bethel MA, et al. Diabetes Care 2017;40:494-501. 4.
Green JB, et al. N Engl J Med 2015;373(3):232-242 . 5. PERKENI. 2015. Panduan Penatalaksanaan DM Tipe 2 pada Individu Dewasa di Bulan Ramadan. 6. International Diabetes
Federation and the DAR International Alliance. 2016. Diabetes and Ramadan: Practical Guidelines. Brussels, Belgium: International Diabetes Federation.
7. Nauck MA, et al. 2007.Diabetes Obes Metab. 2007 Mar;9(2):194-205.

PRODUCT INDICATIONS EFFICACY SAFETY OTHERS HIGHLIGHTS

 SITAGLIPTIN
Doc. No: ID-DSM-00035 Exp.Date : Feb 2023

DOSING RECOMMENDATIONS

PRODUCT INDICATIONS EFFICACY SAFETY OTHERS HIGHLIGHTS

 The recommended dose of SITAGLIPTIN is
100 mg once daily as:
Doc. No: ID-DSM-00035 Exp.Date : Feb 2023

monotherapy Combination Combination

therapy with therapy with
metformin, a sulfonylurea,
metformin plus a
insulin (with or without
sulfonylurea, or
metformin), a PPARγ agonist
metformin plus a
(e.g., thiazolidinediones)
PPARγ agonist

Reference: Local Product Circular. Data on file, MSD Indonesia.

PRODUCT INDICATIONS EFFICACY SAFETY OTHERS HIGHLIGHTS

 The recommended dose of SITAGLIPTIN is
100 mg once daily as:
Doc. No: ID-DSM-00035 Exp.Date : Feb 2023

Once Daily: Twice Daily: Once Daily

• Januvia 50 mg • 50 mg • 50 mg sitagliptin/500 mg
• Januvia 100 mg sitagliptin/500 mg extended-release metformin
metformin hydrochloride
hydrochloride • 50 mg sitagliptin/1000 mg
• 50 mg extended-release metformin
sitagliptin/1000 mg hydrochloride
metformin • 100 mg sitagliptin/1000 mg
hydrochloride extended-release metformin
hydrochloride

Reference: Local Product Circular. Data on file, MSD Indonesia.

PRODUCT INDICATIONS EFFICACY SAFETY OTHERS HIGHLIGHTS

 The recommended dose of SITAGLIPTIN is for
patients with renal impairment:

No 50 mg 25 mg
dosage once once
adjustment
Doc. No: ID-DSM-00035 Exp.Date : Feb 2023

daily daily*

eGFR] ≥45 eGFR ≥30 eGFR ≥ 15 mL/min/1.73 m2 to < 30

mL/min/1.73 m2 to < mL/min/1.73 m2 to mL/min/1.73 m2
90 mL/min/1.73 m2 <45 mL/min/1.73 m2 end-stage renal disease
(eGFR < 15 mL/min/1.73 m2),
including those requiring
hemodialysis or peritoneal dialysis

SITAGLIPTIN may be administered

without regard to the timing of dialysis
*Sitagliptin 25 mg is not marketed in Indonesia
Reference: Local Product Circular. Data on file, MSD Indonesia.

PRODUCT INDICATIONS EFFICACY SAFETY OTHERS HIGHLIGHTS

 SITAGLIPTIN
Doc. No: ID-DSM-00035 Exp.Date : Feb 2023

can be taken should not be

should not be
orally with used for
used in patients
or without patients with
with type 1
food diabetic
diabetes
ketoacidosis

Reference: Local Product Circular. Data on file, MSD Indonesia.

PRODUCT INDICATIONS EFFICACY SAFETY OTHERS HIGHLIGHTS

 More than

142 Million
Prescriptions of
Doc. No: ID-DSM-00035 Exp.Date : Feb 2023

JANUVIA™ and
JANUMET™ Dispensed
Worldwide

Reference: Data on file, MSD.

PRODUCT INDICATIONS EFFICACY SAFETY OTHERS HIGHLIGHTS

 CHOOSE SITAGLIPTIN AS A
FIRST PARTNER TO METFORMIN

+
Doc. No: ID-DSM-00035 Exp.Date : Feb 2023

SITAGLIPTIN + SITAGLIPTIN + TECOS - PROVEN CV OVER 12 YEARS

METFORMIN METFORMIN SAFETY EVEN OF LOCAL
PROVIDED ONCE DAILY FOR HIGH RISK EXPERIENCE 4
POWERFUL HBA1C CONVENIENCE PATIENTS 3
REDUCTIONS, AS AND POWERFUL
MUCH AS -3.6% IN A HbA1c
HIGH-BASELINE HBA1C REDUCTIONS 2
SUBGROUP1

References: 1. Engel, SS et al. Endocr.Pract.2013; 19:751-757. 2. Data on file, MSD Indonesia 3. Green JB et al. NEJM 2015;373(3):232-242.
4. Data on file, MSD.

PRODUCT INDICATIONS EFFICACY SAFETY OTHERS HIGHLIGHTS

 Powerful efficacy
with long-term
Doc. No: ID-DSM-00035 Exp.Date : Feb 2023

experience

PRODUCT INDICATIONS EFFICACY SAFETY OTHERS HIGHLIGHTS

 SELECTED SAFETY INFORMATION ABOUT JANUVIA™
• INDICATIONS AND USAGE

• Monotherapy JANUVIA™
is indicated as an adjunct to diet and exercise to improve glycemic control in patients with type 2 diabetes
mellitus.
• Combination with Metformin or PPARy agonist
Januvia is indicated in patients with type 2 diabetes mellitus to improve glycemic control in combination with
Metformin or a PPARy agonist (i.e. thiazolidinediones) when the single agent alone, with diet and exercise,
does not provide adequate glycemic control.
• Combination with Metformin and Sulfonylurea
Januvia is indicated in patients with type 2 diabetes mellitus to improve glycemic control in combination with
metformin and a sulfonylurea when dual therapy with these agent, with diet and exercise, does not provide
adequate glycemic control.
• Combination with Insulin
Januvia is also indicated as add-on to insulin (with or without metformin) when diet and exercise plus stable
dose of insulin do not provide adequate glycemic control.
When Januvia is used in combination with a sulphonylurea or with insulin, a lower dose of the sulphonylurea or insulin
may be considered to reduce the risk of hypoglycemia
 SELECTED SAFETY INFORMATION ABOUT JANUVIA™

• CONTRAINDICATIONS
None.
• WARNINGS AND PRECAUTIONS

JANUVIA should not be used in patients with type 1 diabetes or for the treatment of diabetic ketoacidosis.

Pancreatitis
There have been postmnarketing reports of acute pancreatitis, including fatal and non-fatal hemorrhagic or
necrotizing pancreatitis (see ADVERSE REACTIONS), in patients taking JANUVIA. After initiation of JANUVIA, patients
should be observed carefully for signs and symptoms of pancreatitis. Patients should be informed of the characteristic
symptom of acute pancreatitis: persistent, severe abdominal pain. Resolution of pancreatitis has been observed after
discontinuation of sitagliptin. If pancreatitis is suspected, JANUVIA, and other potentially suspect medicinal products,
should be discontinued.
 SELECTED SAFETY INFORMATION ABOUT JANUVIA™
• WARNINGS AND PRECAUTIONS (CONT.)

Use in patients with renal impairment

A dosage adjustment is recommended in patients with eGFR< 45 mLmin/1.73 m2), as well as in ESRD patients requiring
hemodialysis or peritoneal dialysis. [See Dosage and Administration, Patients with Renal impairment]
Use with Medications Known to Cause Hypoglycemia
As is typical with other antihyperglycemic agents, hypoglycemia has been observed when JANUVIA was used in
combination with insulin or a sulfonylurea. Therefore, a lower dose of sulfonylurea or insulin may be required to reduce
the risk of hypoglycemia.
Macrovascular Outcomes
There have been no clinical studies establishing conclusive evidence of macrovascular risk reduction with JANUVIA or
any other anti-diabetic drug.
Bullous Pemphigoid
Post marketing cases of bullous pemphigoid requiring hospitalization have been reported with DPP-4 inhibitor use. In
reported cases, patients typically recovered with topical or systemic immunosuppressive treatment and discontinuation
of the DPP-4 inhibitor. Tell patients to report development of blisters or erosions while receiving JANUVIA. If bullous
pemphigoid is suspected, JANUVIA should be discontinued and referral to a dermatologist should be considered for
diagnosis and appropriate treatment.
 SELECTED SAFETY INFORMATION ABOUT JANUMET ™

• INDICATIONS AND USAGE

• JANUMET is indicated as an adjunct to diet and exercise to improve glycemic control in patients with type
2 diabetes mellitus inadequately controlled on metformin or sitagliptin alone or in patients already being
treated with the combination of sitagliptin and metformin.
• JANUMET is also indicated in combination with a sulfonylurea (i.e. triple combination therapy) as an
adjunct to diet and exercise in patients with type 2 DM inadequately controlled with any two of the three
agents: metformin, sitagliptin, or a sulfonylurea.
• JANUMET is also indicated as add-on to insulin (i.e., triple combination therapy) as an adjunct to diet and
exercise to improve glycemic control in patients when stable dose of insulin and metformin alone do not
provide adequate glycemic control. When Januvia is used in combination with a sulphonylurea or with
insulin, a lower dose of the sulphonylurea or insulin may be considered to reduce the risk of hypoglycemia.

When Janumet is used in combination with sulfonylurea or with insulin, a lower dose of sulfonylurea or insulin
may be required to reduce the risk of hypoglycemia.
 SELECTED SAFETY INFORMATION ABOUT JANUMET ™

• CONTRAINDICATIONS
JANUMET (sitagliptin/metformin HCI) is contraindicated in patients with:
• Renal disease or renal dysfunction, e.g., as suggested by serum creatinine levels ≥1.5 mg/dl [males], ≥1.4
mg/dl [females] or abnormal creatinine clearance which may also result from conditions such as
cardiovascular collapse (shock), acute myocardial infarction and septicemia.
• Acute or chronic metabolic acidosis, including diabetic ketoacidosis, with or without coma.
• History of serious hypersensitivity reaction to JANUMET or sitagliptin (one of the components of JANUMET) such
as anaphylaxis or angioedema.
JANUMET should be temporarily discontinued in patients undergoing radiologic studies involving intravascular
administration of iodinated contrast materials, because use of such products may result in acute alteration of renal
function
 SELECTED SAFETY INFORMATION ABOUT JANUMET ™

• WARNING AND PRECAUTIONS

Lactic Acidosis
Metformin hydrochloride
Lactic acidosis is a rare, but serious, metabolic complication that can occur due to metformin accumulation during
treatment with JANUMET; when it occurs, it is fatal in approximately 50% of cases. Lactic acidosis may also occur in
association with a number of pathophysiologic conditions, including diabetes mellitus, and whenever there is significant
tissue hypoperfusion and hypoxemia. Lactic acidosis is characterized by elevated blood lactate levels (>5 mmol/L),
decreased blood pH, electrolyte disturbances with an increased anion gap, and an increased lactate/pyruvate ratio.
When metformin is implicated as the cause of lactic acidosis, metformin plasma levels >5 µglml are generally found.
Pancreatitis
There have been post marketing reports of ac te pancreatitis, including fatal and non-fatal hemorrhagic or necrotizing
pancreatitis in patients taking JANUMET. After initiation of JANUMET, patients should be observed carefully for signs and
symptoms of pancreatitis. Patients should be informed of the characteristic symptom of acute pancreatitis: persistent,
severe abdominal pain. Resolution of pancreatitis has been observed after discontinuation of sitagliptin. If pancreatitis
is suspected, JANUMET, and other potentially suspect medicinal products, should be discontinued.
 SELECTED SAFETY INFORMATION ABOUT JANUMET ™

• WARNING AND PRECAUTIONS

Impaired Hepatic Function
Since impaired hepatic function has been associated with some cases of lactic acidosis, JANUMET should generally be
avoided in patients with clinical or laboratory evidence of hepatic disease.
Monitoring of Renal Function
Metformin and sitagliptin are known to be substantially excreted by the kidney. The risk of metformin accumulation and
lactic acidosis increases with the degree of impairment of renal function. Thus, patients with serum creatinine levels
above the upper limit of normal for their age should not receive JANUMET. In the elderly, JANUMET should be carefully
titrated to establish the minimum dose for adequate glycemic effect, because aging can be associated with reduced
renal function.
Vitamin B12 Levels
In controlled clinical trials of metformin of 29 weeks duration, a decrease to subnormal levels of previously normal serum
Vitamin B12 levels, without clinical manifestations, was observed in approximately 7% of patients. Such decrease,
possibly due to interference with B12 absorption from the B12-intrinsic factor complex, is, however, very rarely
associated with anemia and appears to be rapidly reversible with discontinuation of metformin or Vitamin B12
supplementation.
SELECTED SAFETY INFORMATION ABOUT JANUMET XR ™

• INDICATIONS AND USAGE

• JANUMET XR is indicated as an adjunct to diet and exercise to improve glycemic control in patients with
type 2 diabetes mellitus inadequately controlled on metformin or sitagliptin alone or in patients already
being treated with the combination of sitagliptin and metformin.
• JANUMET XR is also indicated in combination with a sulfonylurea (i.e. triple combination therapy) as an
adjunct to diet and exercise in patients with type 2 DM inadequately controlled with any two of the three
agents: metformin, sitagliptin, or a sulfonylurea.
SELECTED SAFETY INFORMATION ABOUT JANUMET XR ™

• CONTRAINDICATIONS
JANUMET (sitagliptin/metformin HCI) is contraindicated in patients with:
• Renal disease or renal dysfunction, e.g., as suggested by serum creatinine levels ≥1.5 mg/dl [males], ≥1.4
mg/dl [females] or abnormal creatinine clearance which may also result from conditions such as
cardiovascular collapse (shock), acute myocardial infarction and septicemia.
• Acute or chronic metabolic acidosis, including diabetic ketoacidosis, with or without coma.
• History of serious hypersensitivity reaction to JANUMET XR or sitagliptin (one of the components of JANUMET XR )
such as anaphylaxis or angioedema.
JANUMET XR should be temporarily discontinued in patients undergoing radiologic studies involving intravascular
administration of iodinated contrast materials, because use of such products may result in acute alteration of renal
function
SELECTED SAFETY INFORMATION ABOUT JANUMET XR ™

• WARNING AND PRECAUTIONS

Lactic Acidosis
Metformin hydrochloride
Lactic acidosis is a rare, but serious, metabolic complication that can occur due to metformin accumulation during
treatment with JANUMET; when it occurs, it is fatal in approximately 50% of cases. Lactic acidosis may also occur in
association with a number of pathophysiologic conditions, including diabetes mellitus, and whenever there is significant
tissue hypoperfusion and hypoxemia. Lactic acidosis is characterized by elevated blood lactate levels (>5 mmol/L),
decreased blood pH, electrolyte disturbances with an increased anion gap, and an increased lactate/pyruvate ratio.
When metformin is implicated as the cause of lactic acidosis, metformin plasma levels >5 µglml are generally found.
Pancreatitis
There have been post marketing reports of ac te pancreatitis, including fatal and non-fatal hemorrhagic or necrotizing
pancreatitis in patients taking JANUMET. After initiation of JANUMET, patients should be observed carefully for signs and
symptoms of pancreatitis. Patients should be informed of the characteristic symptom of acute pancreatitis: persistent,
severe abdominal pain. Resolution of pancreatitis has been observed after discontinuation of sitagliptin. If pancreatitis
is suspected, JANUMET, and other potentially suspect medicinal products, should be discontinued.
SELECTED SAFETY INFORMATION ABOUT JANUMET XR ™

• WARNING AND PRECAUTIONS

Impaired Hepatic Function
Since impaired hepatic function has been associated with some cases of lactic acidosis, JANUMET should generally be
avoided in patients with clinical or laboratory evidence of hepatic disease.
Monitoring of Renal Function
Metformin and sitagliptin are known to be substantially excreted by the kidney. The risk of metformin accumulation and
lactic acidosis increases with the degree of impairment of renal function. Thus, patients with serum creatinine levels
above the upper limit of normal for their age should not receive JANUMET. In the elderly, JANUMET should be carefully
titrated to establish the minimum dose for adequate glycemic effect, because aging can be associated with reduced
renal function.
Vitamin B12 Levels
In controlled clinical trials of metformin of 29 weeks duration, a decrease to subnormal levels of previously normal serum
Vitamin B12 levels, without clinical manifestations, was observed in approximately 7% of patients. Such decrease,
possibly due to interference with B12 absorption from the B12-intrinsic factor complex, is, however, very rarely
associated with anemia and appears to be rapidly reversible with discontinuation of metformin or Vitamin B12
supplementation.
 For Healthcare Professional Only
Copyright 2021 PT MSD Indonesia.,
a subsidiary of Merck & Co., Inc. Kenilworth. NJ, USA. All rights reserved.

PT MSD Indonesia. Wisma 46 Building 27th Fl. Jl. Jend. Sudirman No.Kav. 1,
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Daerah Khusus Ibukota Jakarta 10220

Tel. +62 21 5789 7000 https://www.msd-indonesia.com/

Any report or enquiry related MSD Product Adverse Event, Product Quality
Complaint, and etc. please email: Email: dpoc.indonesia@merck.com

Doc. No: ID-DSM-00035

Exp.Date : Feb 2023