WHITEHOUSE STATION, N.J., June 9, 2012 – Merck (NYSE: MRK) (known as MSD outside the United States and Canada) today announced results of a post-hoc pooled analysis in which patients with type 2 diabetes age 65 or older treated with JANUVIA® (sitagliptin) 100 mg/day achieved similar blood sugar reductions as those treated with a sulfonylurea, with significantly less hypoglycemia (low blood sugar).
JANUVIA is indicated, as an adjunct to diet and exercise, to improve glycemic control in adults with type 2 diabetes mellitus. JANUVIA should not be used in patients with type 1 diabetes or for the treatment of diabetic ketoacidosis. JANUVIA has not been studied in patients with a history of pancreatitis. It is unknown whether patients with a history of pancreatitis are at increased risk of developing pancreatitis while taking JANUVIA.
"The general effects of aging complicate the treatment of diabetes in the elderly; in particular, hypoglycemia is of greater concern in this population and may lead to dizziness and accidents or falls, which are more likely to be dangerous in the elderly," said Barry J. Goldstein, M.D., Ph.D., Vice President and Therapeutic Area Head, Diabetes and Endocrinology, Merck Research Laboratories. "Therefore, careful consideration of treatment options for older patients is important."
Hypoglycemia can be more of a challenge in elderly patients and recognition of the symptoms of hypoglycemia may be diminished. Symptoms that may be caused by low blood sugar include: nervousness or anxiety, shakiness, sweating, tiredness, confusion, hunger and dizziness.
Nearly 26 million people in the United States (8.3 percent of the population) have diabetes, and 90 to 95 percent of diagnosed cases of diabetes are type 2 diabetes. According to the American Diabetes Association, of those with diabetes, 10.9 million people are age 65 years or older.
JANUVIA is a selective, once-daily DPP-4 inhibitor that increases active GLP-1 and GIP hormones, part of a natural body system called the incretin system to help regulate blood sugar. JANUVIA inhibits the DPP-4 enzyme over 24 hours. JANUVIA is the first approved compound in the DPP-4 inhibitor class of oral treatments. JANUVIA has been approved in more than 107 countries, and to date, more than 42.5 million prescriptions have been dispensed for the sitagliptin family of products worldwide.
Selected Important Risk Information About JANUVIA JANUVIA is contraindicated in patients with a history of a serious hypersensitivity reaction to sitagliptin, such as anaphylaxis or angioedema.
There have been postmarketing reports of acute pancreatitis, including fatal and nonfatal hemorrhagic or necrotizing pancreatitis, in patients taking JANUVIA. After initiating JANUVIA, observe patients carefully for signs and symptoms of pancreatitis. If pancreatitis is suspected, promptly discontinue JANUVIA and initiate appropriate management. It is unknown whether patients with a history of pancreatitis are at increased risk of developing pancreatitis while taking JANUVIA.
About the post-hoc analysis This post-hoc analysis pooled data of elderly patients that completed trials through 30 weeks from three double-blind clinical studies of sitagliptin 100 mg/day (as monotherapy and in combination with metformin) compared to sulfonylureas (in titrated doses; glipizide or glimepiride). The analysis compared the effects of JANUVIA 100 mg once daily or a sulfonylurea (in titrated doses) on change from baseline in A1C, fasting plasma glucose, body weight and the proportion of patients that experienced one or more episodes of symptomatic hypoglycemia. In two studies, patients on diet alone or metformin were randomized to receive JANUVIA 100 mg/day (as a monotherapy or in combination with metformin) or the sulfonylurea glipizide (as a monotherapy or in combination with metformin) for 104 weeks, and in the third study patients were randomized to receive JANUVIA or the sulfonylurea glimepiride for 30 weeks. Since the third study was 30 weeks in duration, the analysis focused on results at or close to 30 weeks and included the 373 elderly patients who completed the trials through this time point.
Elderly patients taking JANUVIA 100 mg/day (n=178; 0.73 percent LS mean A1C reduction from a baseline of 7.5 percent) achieved similar blood sugar reductions as patients taking a sulfonylurea (n=195; 0.78 LS mean percent A1C reduction from a baseline of 7.5 percent). Of the patients taking a sulfonylurea, 28.2 percent experienced one or more episodes of symptomatic hypoglycemia, compared to 6.2 percent of patients taking JANUVIA.
Selected Important Risk Information About JANUVIA Assessment of renal function is recommended prior to initiating JANUVIA and periodically thereafter. A dosage adjustment is recommended in patients with moderate or severe renal insufficiency and in patients with end-stage renal disease requiring hemodialysis or peritoneal dialysis. Caution should be used to ensure that the correct dose of JANUVIA is prescribed.
No dosage adjustment is required based on age; however, because JANUVIA is substantially excreted by the kidney, it may be useful to assess renal function in elderly patients before initiation and periodically thereafter.
No overall differences in safety or effectiveness were observed between subjects 65 years and over and younger subjects. While this and other reported clinical experience have not been identified differences in responses between the elderly and younger patients, greater sensitivity of some older individuals cannot be ruled out.
This drug is known to be substantially excreted by the kidney. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection in the elderly, and it may be useful to assess renal function in these patients prior to initiating dosing and periodically thereafter.
There have been postmarketing reports of worsening renal function, including acute renal failure, sometimes requiring dialysis. A subset of these reports involved patients with renal insufficiency, some of whom were prescribed inappropriate doses of sitagliptin.
When JANUVIA was used in combination with a sulfonylurea or insulin, medications known to cause hypoglycemia, the incidence of hypoglycemia was increased over that of placebo. Therefore, a lower dose of sulfonylurea or insulin may be required to reduce the risk of hypoglycemia.
The incidence (and rate) of hypoglycemia based on all reports of symptomatic hypoglycemia were: 12.2% (0.59 episodes/patient-year) for JANUVIA 100 mg in combination with glimepiride (with or without metformin), 1.8% (0.24 episodes/patient-year) for placebo in combination with glimepiride (with or without metformin), 15.5% (1.06 episodes/patient-year) for JANUVIA 100 mg in combination with insulin (with or without metformin), and 7.8% (0.51 episodes/patient-year) for placebo in combination with insulin (with or without metformin).
There have been postmarketing reports of serious hypersensitivity reactions in patients treated with JANUVIA, such as anaphylaxis, angioedema, and exfoliative skin conditions including Stevens-Johnson syndrome. Onset of these reactions occurred within the first 3 months after initiation of treatment with JANUVIA, with some reports occurring after the first dose. If a hypersensitivity reaction is suspected, discontinue JANUVIA, assess for other potential causes for the event, and institute alternative treatment for diabetes.
Angioedema has also been reported with other dipeptidyl peptidase-4 (DPP-4) inhibitors. Use caution in a patient with a history of angioedema with another DPP-4 inhibitor because it is unknown whether such patients will be predisposed to angioedema with JANUVIA.
There have been no clinical studies establishing conclusive evidence of macrovascular risk reduction with JANUVIA or with any other antidiabetic drug.
In clinical studies, the adverse reactions reported, regardless of investigator assessment of causality, in ≥5% of patients treated with JANUVIA as monotherapy and in combination therapy and more commonly than in patients treated with placebo, were upper respiratory tract infection, nasopharyngitis, and headache.