FDA approves Merck’s Juvisync, the first combination drug to treat type 2 diabetes and high cholesterol in one table

WHITEHOUSE STATION, N.J.—Keeping in mind thatmultiple national guidelines recommend patients with type 2 diabetes be treatedfor cholesterol problems as well, Merck & Co. developed a combination of sitagliptinand simvastatin under the name Juvisync—a drug that received U.S. Food and DrugAdministration (FDA) approval this month.

Merck, which is known as MSD outside the UnitedStates and Canada, notes that this is the first treatment option for healthcareproviders to help patients who need the blood sugar-lowering benefits of a dipeptidylpeptidase 4 (DPP-4) inhibitor and the cholesterol-lowering benefits ofsimvastatin, with the convenience of a single tablet once daily.

"Although clinical guidelines put people with type2 diabetes who need glycemic and lipid therapy at the same risk level as thosewith coronary heart disease, nearly 40 percent of eligible patients do notreceive statin treatment," said Dr. Barry J. Goldstein, vice president for diabetesand endocrinology at Merck. "We are proud to bring forward a treatment optionthat can help these patients who need both glycemic and lipid therapy."

The FDA describes the drug, in its new releaseabout the approval, as "a fixed-dose combination (FDC) prescription medicationthat contains two previously approved medicines in one tablet for use in adultswho need both sitagliptin and simvastatin." Some 20 million people in theUnited States have type 2 diabetes, the FDA notes, and they often have highcholesterol levels as well. These conditions can lead to increased risk ofheart disease, stroke, kidney disease, blindness and other chronic conditions,particularly if left untreated or poorly treated.

Sitagliptin is a DPP-4 inhibitor that enhances one'sability to lower elevated blood sugar and had previously been approved for usein combination with diet and exercise to improve glycemic control in adultswith type 2 diabetes. Simvastatin is an HMG-CoA reductase inhibitor, or statin,that had been approved for use with diet and exercise to reduce the amount of low-density lipoprotein (LDL) cholesterol—colloquiallyreferred to as "bad cholesrerol"—in the blood.

"This is the first product to combine a type 2 diabetesdrug with a cholesterol-lowering drug in one tablet," said Dr. Mary H. Parks, directorof the Division of Metabolism and Endocrinology Products in the FDA's Centerfor Drug Evaluation and Research. "However, to ensure safe and effective use ofthis product, tablets containing different doses of sitagliptin and simvastatinin fixed-dose combination have been developed to meet the different needs ofindividual patients. Dose selection should factor in what other drugs thepatient is taking."

The FDA maintains that this FDC "is based onsubstantial experience with both sitagliptin and simvastatin, and the abilityof the single tablet to deliver similar amounts of the drugs to the bloodstreamas when sitagliptin and simvastatin are taken separately." Furthermore, theagency calls Juvisync "a convenience combination" and notes that it should onlybe prescribed when it is appropriate for a patient to be placed on both drugs.

Juvisync was approved in dosage strengths forsitagliptin/simvastatin of 100 mg/10 mg, 100 mg/20 mg and 100 mg/40 mg. Merckreportedly has committed to develop FDC tablets with the sitagliptin 50 mgdose, as Juvisync 50 mg/10 mg, 50 mg/20 mg and 50 mg/40 mg. Pendingavailability of the FDC tablets containing 50 mg of sitagliptin, patients whorequire this dose should continue to use the single-ingredient sitagliptintablet. There is no plan to develop FDCs with the sitagliptin 25 mg dose, theFDA reports, "as use of this dose is quite low."

Simvastatin is currently marketed in dosagestrengths of 5, 10, 20, 40, and 80 mg. Due to recent restrictions placed on theuse of the 80 mg dose because of a higher risk of muscle toxicity, there willnot be a FDC using this dose, the FDA notes. There is also no plan to developFDCs with the simvastatin 5 mg dose as use of this dose is quite low as well.

The FDA notes that it has recently become aware ofthe potential for statins to increase blood sugar levels in patients with type2 diabetes, and says, "This risk appears very small and is outweighed by thebenefits of statins for reducing heart disease in diabetes. However, theprescribing information for Juvisync will inform doctors of this possible sideeffect. The company will also be required to conduct a post-marketing clinicaltrial comparing the glucose lowering ability of sitagliptin alone compared tositagliptin given with simvastatin."

Juvisync should not be used in patients with type1 diabetes or for the treatment of diabetic ketoacidosis, as it would not beeffective in these settings, Merck warns, also noting that Juvisync has notbeen studied in patients with a history of pancreatitis—so it remains unknownwhether patients with a history of pancreatitis are at increased risk ofdeveloping pancreatitis while taking the drug. Also, because doses of Juvisync appropriatefor patients with moderate or severe renal impairment (CrCl <50 mL/min,approximately corresponding to serum creatinine levels of >1.7 mg/dL in menand >1.5 mg/dL in women) or end-stage renal disease (ESRD) are not availablein this combination product, Juvisync is not recommended in patients withmoderate or severe renal impairment or ESRD, Merck notes.