Drug reference

Metformin + Sitagliptin

Antidiabetic fixed-dose combination (biguanide + DPP-4 inhibitor) · Antidiabetic

Also known as Janumet, Istamet, Glycip-M, Sitaglip-M

START

Sitagliptin 50 mg/metformin 500 mg PO twice daily with food

TYPICAL MAX

Sitagliptin 100 mg + metformin 2000 mg/day

STOP IF

eGFR <30, acidosis, pancreatitis, or severe hypersensitivity

WATCH

Renal function/eGFR, GI tolerance, pancreatitis symptoms

CDSCO approvedSchedule HATC A10BD07

Dose laddermg/d

Renal dose adjustmenteGFR mL/min/1.73m²

KDIGO 2024 + manufacturer label

Pharmacokineticsplasma · t hours

ONSET: 1h · absorption
PEAK: 2.5h · Tmax
t½: 12h · sitagliptin t½
DURATION: 12h · twice-daily

EXCRETION

Both predominantly renal (unchanged)

route + CYP

INTERACTIONS

1 major

SEVERE in our sources

PREGNANCY

Insulin generally preferred in pregnancy; use only if clearly appropriate.

FDA category + note

Top interactionssee all 5 →

Iodinated Contrast MediaSevereDatabaseKimi deep-research + Cla

Mechanism

Metformin reduces hepatic gluconeogenesis and improves insulin sensitivity (AMPK-mediated); sitagliptin inhibits DPP-4, raising incretin (GLP-1/GIP) levels to enhance glucose-dependent insulin secretion and suppress glucagon — complementary glucose lowering with low intrinsic hypoglycaemia risk.

Indications

US JANUMET: adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes; not for type 1 diabetes.

Dosing

Adult: Sitagliptin 50 mg/metformin 500 or 1000 mg PO twice daily with meals (total sitagliptin 100 mg/day); titrate metformin to tolerance.
Pediatric: Not established for the combination.
Renal adjustment: US JANUMET IR is not recommended at eGFR 30 to <45 mL/min/1.73 m² because the required lower sitagliptin dose is unavailable in this fixed combination; contraindicated below 30. Assess renal function before starting and periodically.
Hepatic adjustment: Avoid metformin in significant hepatic impairment (lactic acidosis risk).
Geriatric: Assess renal function; conservative dosing.
Max dose: Sitagliptin 100 mg/day + metformin 2000 mg/day

Pharmacokinetics

Onset

Glucose lowering over days

Peak effect

Sitagliptin Tmax ~1–4 h; metformin ~2.5 h

Duration

~12 h (twice-daily)

Half-life

US JANUMET IR label: Sitagliptin terminal half-life is about 12.4 hours; metformin plasma half-life about 6.2 hours and blood half-life about 17.6 hours.

Bioavailability

Sitagliptin ~87%; metformin ~50–60%

Protein binding

Sitagliptin ~38%; metformin negligible

Metabolism

Sitagliptin minimal (mostly unchanged); metformin not metabolised

Excretion

Both predominantly renal (unchanged)

Contraindications

eGFR <30 mL/min/1.73m² (metformin — lactic acidosis)
Acute metabolic acidosis / diabetic ketoacidosis
Acute conditions risking renal hypoperfusion / hypoxia
Hypersensitivity to either component
Iodinated-contrast: temporarily withhold metformin per protocol

Side effects

Common

Diarrhoea/GI upset (metformin)NauseaHeadacheNasopharyngitisHypoglycaemia (mainly with insulin/sulfonylurea)

Serious

Lactic acidosis (metformin — rare, serious)
Acute pancreatitis (sitagliptin)
Severe hypersensitivity / SJS / angioedema
Severe joint pain (DPP-4 class)
Bullous pemphigoid

Pregnancy & lactation

Pregnancy

Insulin generally preferred in pregnancy; use only if clearly appropriate.

Lactation

US JANUMET IR label: No information on JANUMET in human milk or breastfed infant effects. Metformin occurs in milk; sitagliptin occurs in rat milk. Consider breastfeeding benefits, maternal need and potential infant effects.