Comparison table

Drug class Sodium-glucose co-transporter 2 (SGLT2) inhibitors Dipeptidyl peptidase-4 (DPP-4) inhibitors
Mechanism of Increase urinary excretion of glucose Increase glucose-dependent insulin
action secretion
Decrease glucagon secretion
Drugs Dapagliflozin Sitagliptin; Linagliptin
Indication as dual therapy Adjunct to diet and exercise to improve
o in combination with metformin for patients with glycemic control in adults with type 2
HbA1c measurement greater than 7% despite diabetes mellitus as
treatment with metformin monotherapy and monotherapy
when sulfonylureas are contraindicated or not add on to metformin
tolerated or the person is at significant risk of add on to sulphonylurea
hypoglycaemia or its consequences; or add on to insulin (with or without
o in combination with a sulfonylurea for patients metformin) add on to metformin plus
with HbA1c measurement greater than 7% despite sulphonylurea
treatment with sulfonylurea monotherapy and
when metformin is contraindicated or not
tolerated; or
as a triple therapy
o in combination with metformin and a
sulfonylurea for patients with HbA1c
measurement greater than 7% despite treatment
with optimal doses of dual therapy.
as monotherapy (not approved MAF use criteria)
o only for patients with HbA1c measurement
greater than 7% despite lifestyle measure and
where the use of metformin and sulphonylureas is
contraindicated or not tolerated.
as combination therapy with insulin
o in combination with insulin with or without other
anti-diabetic drugs for patients with HbA1c
measurement greater than 7% despite treatment
with optimal doses of other anti-diabetic drugs

Adult dose Initiate at 5mg and titrate as needed to 10mg once daily Sitagliptin : Up to 100mg once daily
For patients at risk for volume depletion due to co-existing Linagliptin 5mg once daily
conditions, a 5 mg starting dose may be appropriate
Administration Taken once daily without regard to meals Taken once daily without regard to meals
Dose adjustment: Assess kidney function prior to starting dapagliflozin and Sitagliptin
Renal impairment monitor periodically thereafter. CrCl 50 mL/minute: No dosage
CrCl or eGFR 60 mL/minute/1.73 m2: No dosage adjustment necessary. 100 mg once
adjustment necessary. daily
CrCl or eGFR 30 to <60 mL/minute/1.73 m2: Use is not CrCl 30 to <50 mL/minute
recommended for initiation of therapy or when eGFR is (approximate SCr of >1.7 to 3 mg/dL
persistently between 30 and <60 mL/minute/1.73 m2. [males] or >1.5 to 2.5 mg/dL
CrCl or eGFR <30 mL/minute/1.73 m2: Use is [females]): 50 mg once daily
contraindicated. CrCl <30 mL/minute (approximate SCr
ESRD: Use is contraindicated. of >3 mg/dL [males] or >2.5 mg/dL
Hemodialysis: Use is contraindicated. [females]): 25 mg once daily
ESRD requiring hemodialysis or
peritoneal dialysis: 25 mg once daily;
administer without regard to timing
of hemodialysis

Linagliptin: No dosage adjustment

necessary.
Drug class Sodium-glucose co-transporter 2 (SGLT2) inhibitors Dipeptidyl peptidase-4 (DPP-4) inhibitors
Dose adjustment: Mild to moderate hepatic impairment: No dosage adjustment Sitagliptin
Hepatic impairment necessary Mild to moderate impairment
Severe hepatic impairment: Should not be used (no (Child-Pugh classes A and B): No
information) dosage adjustment necessary.
Severe impairment (Child-Pugh
class C): use has not been studied

Linagliptin: No dosage adjustment

necessary.
Cost Sitagliptin (Januvia)
Dapagliflozin (Forxiga) 100mg tablet $ 2.57/tablet
10mg tablet $1.36/tablet 50mg tablet $ 2.57/tablet

Linagliptin (Trajenta)
5mg tablet $ 1.71/tablet

Contraindication -History of serious hypersensitivity to dapagliflozin or any Hypersensitivity to the active ingredient
component of the formulation or any of the excipients
-Renal impairment (eGFR <60 mL/minute/1.73 m2)
-End-stage renal disease (ESRD), or patients on dialysis
-Restarting SGLT2 inhibitor treatment in patients with previous
diabetic ketoacidosis (DKA) while on SGLT2 inhibitor treatment
is not recommended (unless another clear precipitating factor
was identified and resolved)
-Not recommended for use in patients receiving loop diuretics
or who are volume depleted due to acute illness

Cautions Caution should be exercised in patients for whom a

dapagliflozin-induced drop in blood pressure could pose a risk,
such as patients with known cardiovascular disease, renal
impairment, patients on anti-hypertensive therapy with a
history of hypotension or elderly patients
Fasting plasma Moderate Mild
glucose lowering
Postprandial glucose Mild Moderate
lowering
Hypoglycemia risk Neutral Neutral
Weight Loss Neutral
Genitourinary May increase the risk of genital mycotic infections Nil
Cardiac Possible CV benefit (evidence for empagliflozin, unknown if Neutral (possible risk for saxagliptin)
other SGLT2 inhibitors will have similar CVD effects) Unclear if the risk is specific to certain
May increase LDL DPP-4 inhibitors and whether it extends
Blood pressure reduction to patients without CVD.
Bone May increase risk of bone fractures (Warning for canagliflozin) Neutral
Ketoacidosis Risk of DKA in stress settings Neutral
Arthralgia Nil Severe and disabling arthralgia has been
reported with DPP-IV inhibitor use; onset
may occur within one day to years after
treatment initiation and may resolve with
discontinuation of therapy. Some patients
may experience a recurrence of
symptoms if DPP-IV inhibitor therapy
resumed
Pancreatitis Nil Cases of acute pancreatitis, including
fatalities, have been reported with use
Prepared by Dr Nor Izuan on 17 April 2017

Reviewed by Tan Beng Li, NHG Pharmacy, Drug Information Service, 21 April 2017

References used
Lexicomp Drug Information: Dapagliflozin, Sitagliptin, Linagliptin
Product inserts: Forxiga, Januvia, Trajenta
American Association of Clinical Endocrinologists and American College of Endocrinology Clinical Practice Guidelines for
Developing a Diabetes Mellitus Comprehensive Care Plan. ENDOCRINE PRACTICE Vol 21 No. 4 April 2015