sitagliptin (Rx)

>10%

Combination with insulin with or without metformin

• Hypoglycemia (15.5%)

Combination with glimepiride with or without metformin

• Hypoglycemia (12.2%)

1-10%

Monotherapy

• Nasopharyngitis (5.2%)
• Upper respiratory tract infection (4.5%)
• Headache (1.1%)

Combination with pioglitazone

• Upper respiratory tract infection (6.3%)
• Headache (5.1%)

Combination with metformin

• Nasopharyngitis (6.2%)
• Upper respiratory tract infection (5.9%)

Combination with metformin and rosiglitazone

• Nasopharyngitis (6.1%)
• Upper respiratory tract infection (5.5%)

Combination with glimepiride with or without metformin

• Nasopharyngitis (6.3%)
• Upper respiratory tract infection (5.9%)

Postmarketing Reports

Hypersensitivity reactions including anaphylaxis, angioedema, rash, urticaria, cutaneous vasculitis, and exfoliative skin conditions including Stevens-Johnson syndrome

Hepatic enzyme elevations; acute pancreatitis, including fatal and nonfatal hemorrhagic and necrotizing pancreatitis

Worsening renal function, including acute renal failure (sometimes requiring dialysis)

Severe and disabling arthralgia

Constipation, vomiting

Headache, myalgia, pain in extremity, back pain

Rhabdomyolysis

Pruritus

Bullous pemphigoid

Mouth ulceration; stomatitis

Contraindications

Serious hypersensitivity to sitagliptin (eg, anaphylaxis, angioedema)

Cautions

Acute pancreatitis reported, including fatal and nonfatal hemorrhagic or necrotizing pancreatitis; if pancreatitis suspected, discontinue promptly

Acute renal failure reported, sometimes requiring dialysis; assess renal function before initiation and periodically thereafter

Serious allergic and hypersensitivity reactions (eg, anaphylaxis, angioedema, exfoliative skin conditions including Stevens-Johnson syndrome) reported; promptly stop treatment and assess for other potential causes; appropriately monitor and treat

Severe and disabling arthralgia reported in patients taking DPP-4 inhibitors; consider as a possible cause for severe joint pain and discontinue drug if appropriate

Heart failure observed with other DPP-4 inhibitors; consider risks and benefits in patients with risk factors for heart failure; monitor for signs and symptoms; if heart failure develops, manage accordingly to standard of care and consider interrupting treatment

Bullous pemphigoid reported with DPP-4 inhibitor use, which required hospitalization; in reported cases, patients recovered with topical or systemic immunosuppressive treatment and discontinuation of DPP-4 inhibitor; advise to report any developing blisters/erosions; discontinue DPP-4 therapy and consult a dermatologist if bullous pemphigoid suspected

Drug interaction overview

• Sitagliptin is a P-gp and organic anion transporter-3 substrate; weak CYP3A4 and CYP2C8 substrates

• Insulin or insulin secretagogues

  • Increased risk of hypoglycemia when concomitantly used with insulin and/or an insulin secretagogue; consider lowering dose of insulin or insulin secretagogue

Pregnancy

Limited available data in pregnant females are not sufficient to inform a drug-associated risk for major birth defects and miscarriage

Pregnancy registry

• Monitors pregnancy outcomes in females exposed to drug during pregnancy
• Encourage patients to report any prenatal exposure to drug by calling 1-800-986-8999

Animal data

• No adverse developmental effects were observed when administered to pregnant rats and rabbits during organogenesis at oral doses up to 30x and 20x, respectively, the 100-mg clinical dose, based on AUC

Clinical considerations

• Poorly controlled diabetes in pregnancy increases maternal risk for diabetic ketoacidosis, preeclampsia, spontaneous abortions, preterm delivery, still birth, and delivery complications
• Poorly controlled diabetes increases fetal risk for major birth defects, stillbirth, and macrosomia related morbidity

Lactation

There is no information regarding presence of drug in human milk, effects on breastfed infants, or on milk production

Present in rat milk and therefore possibly present in human

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of Action

Dipeptyl peptidase-IV (DPP-4) inhibitor; increases and prolongs incretin hormone activity, which is inactivated by DPP-4 enzyme

Incretins increase insulin release and synthesis from pancreatic beta cells and reduce glucagon secretion from pancreatic alpha cells

Absorption

Bioavailability: 87%

Peak plasma time: 1-4 hr

Peak plasma concentration: 950 nM (single oral 100-mg dose)

AUC: 8.52 microM·hr (single oral 100-mg dose)

Distribution

Protein bound: 38%

Vd: 198 L

Metabolism

Limited; primarily via CYP3A4 and CYP2C8

Elimination

Renal clearance: 350 mL/min

Half-life, terminal: 12.4 hr

Excretion: Urine (87% [79% unchanged]), feces (13%)

Oral Administration

Take with or without food

Swallow tablet whole; do not chew, crush, or split

Storage

Store at 20-25ºC (68-77ºF), excursions permitted to 15-30ºC (59-86ºF)