Ertugliflozin + Sitagliptin

Indications

Ertugliflozin + Sitagliptin is used for: Type 2 Diabetes Mellitus

Adult Dose

Type 2 Diabetes Mellitus Indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus when treatment with both ertugliflozin and sitagliptin is appropriate 5 mg/100 mg PO qDay in morning initially; if additional glycemic control is needed and starting dose is tolerated, may increase to maximum dose of 15 mg/100 mg Patients on ertugliflozin: Maintain ertugliflozin dose when switched to combination Hepatic impairment Mild-to-moderate: No dosage adjustment necessary Severe: Not recommended

Child Dose

<18 years: Safety and efficacy not established

Renal Dose

Renal impairment eGFR ?60 mL/min/1.73 m²: No dosage adjustment necessary eGFR <30 mL/min/1.73 m²: Contraindicated End-stage renal disease or dialysis: Contraindicated eGFR 30-60 mL/min/1.73 m² Initiation of ertugliflozin not recommended Continued use not recommended with persistent eGFR 30-60 mL/min/1.73 m²

Administration

Take in the morning qDay, with or without food

Contra Indications

Hypersensitivity Severe renal impairment, end-stage renal disease, or dialysis

Precautions

Acute pancreatitis, including fatal and nonfatal hemorrhagic or necrotizing pancreatitis, in patients taking sitagliptin reported; promptly discontinue if pancreatitis suspected Necrotizing fasciitis of the perineum (Fournier gangrene) reported with SGLT2 inhibitors; signs and symptoms include tenderness, redness, or swelling of the genitals or the area from the genitals back to the rectum, and have a fever above 100.4 F or a general feeling of being unwell; if suspected, discontinue SGLT2 inhibitor and start treatment immediately with broad-spectrum antibiotics and surgical debridement if necessary Causes intravascular volume contraction; symptomatic hypotension may occur after initiating, particularly in patients with renal impairment, with low systolic blood pressure, on diuretics, or who are elderly Ketoacidosis, a serious life-threatening condition requiring urgent hospitalization, reported; before initiating, consider factors that may predispose patient to ketoacidosis, including pancreatic insulin deficiency from any cause, caloric restriction, and alcohol abuse; monitor for ketoacidosis and temporarily discontinue in clinical situations known to predispose to ketoacidosis (eg, prolonged fasting owing to acute illness or surgery) Serious urinary tract infections, including urosepsis and pyelonephritis, requiring hospitalization reported in patients receiving SGLT2 inhibitors

Pregnancy-Lactation

Pregnancy Ertugliflozin Based on animal data showing adverse renal effects, not recommended during the second and third trimesters of pregnancy Data are limited in pregnant women and are not sufficient to determine a drug-associated risk of adverse developmental outcomes; there are risks to the mother and fetus associated with poorly controlled diabetes in pregnancy Animal data In animal studies, adverse renal changes were observed in rats when ertugliflozin was administered during a period of renal development corresponding to the late second and third trimesters of human pregnancy; doses ~13 times the maximum clinical dose caused renal pelvic and tubule dilatations and renal mineralization that were not fully reversible There was no evidence of fetal harm in rats or rabbits at exposures of ertugliflozin ~300 times higher than the maximal clinical dose of 15 mg/day when administered during organogenesis Sitagliptin There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to sitagliptin during pregnancy Health care providers are encouraged to report any prenatal exposure by calling the Pregnancy Registry at 1-800-986-8999 Lactation Not recommended while breastfeeding Unknown if distributed in human breast milk Since human kidney maturation occurs in utero and during the first 2 years of life when lactational exposure may occur, there may be risk to the developing human kidney Because of the potential for serious adverse reactions in a breastfed infant, advise women that ertugliflozin/sitagliptin is not recommended while breastfeeding

Interactions

Adverse Effects

Side effects of Ertugliflozin + Sitagliptin : >10% (Ertugliflozin) Female genital mycotic infections (9.1-12.2%) 1-10% (Ertugliflozin) Volume depletion adverse effects (1.9-4.4%) Male genital mycotic infections (3.7-4.2%) Urinary tract infections (4-4.1%) Headache (2.9-3.5%) Vaginal pruritus (2.4-2.8%) Increased urination (2.4-2.7%) Nasopharyngitis (2-2.5%) Back pain (1.7-2.5%) Renal adverse effects (1.3-2.5%) Weight decreased (1.2-2.4%) Thirst (1.4-2.7%) Frequency Not Defined (Sitagliptin) Upper respiratory tract infection Nasopharyngitis Headache Abdominal pain Nausea Diarrhea Peripheral edema

Mechanism of Action

Ertugliflozin: Selective sodium-glucose transporter-2 (SGLT2) inhibitor; lowers the renal glucose threshold (ie, the plasma glucose concentration which exceed the maximum glucose reabsorption capacity of the kidney); lowering the renal glucose threshold results in increased urinary glucose excretion Sitagliptin: 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