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Pooled Analysis: Fewer Major Adverse Cardiovascular Events in People with Type 2 Diabetes Treated with Merck Sharp & Dohme (MRK)'s JANUVIA ® (sitagliptin)

12/6/2011 11:17:57 AM

DUBAI, UNITED ARAB EMIRATES, 6 December 2011 – In a pooled analysis presented at this week’s International Diabetes Federation (IDF) 21st World Diabetes Congress, a lower incidence of reported major cardiovascular events (MACE)* was observed in patients with type 2 diabetes treated with sitagliptin compared to those treated with a sulphonylurea (SU).

In this pooled analysis of cardiovascular (CV) safety data from three previously published randomized, blinded clinical studies, which included patients with type 2 diabetes who had been randomized to either sitagliptin 100 mg/day (n = 1,226), or an SU (glipizide or glimepiride, n = 1,225) as monotherapy or add-on to metformin, there were no reports of a major adverse CV event (i.e., ischemic events and CV deaths) in the sitagliptin group, and 11 patients in the SU group were reported to have experienced at least one major adverse CV event.

“Although a retrospective pooled analysis with distinct limitations, this analysis shows that patients with type 2 diabetes treated with sitagliptin had fewer major adverse cardiovascular events compared to patients treated with sulphonylureas,” said Barry J. Goldstein, M.D., Ph.D., vice president, Diabetes and Endocrinology, Merck. “These data are important, but prospective studies are needed. Results of a previously published pooled analysis of 19 clinical trials to evaluate the safety and tolerability of sitagliptin did not show an increased risk of CV events with sitagliptin 100 mg/day compared to placebo or other medicines.”

Study design

Custom MACE events included collected adverse experience reports related to ischemic events and CV deaths were assessed by pooling three double-blind studies, which randomized patients at baseline to sitagliptin 100 mg/day (n = 1,226) or an SU (n = 1,225). Two trials evaluated these agents when added to ongoing metformin therapy (30 weeks in duration [glimepiride] and 104 weeks [glipizide]). The third study was a monotherapy trial that was 104 weeks in duration [glipizide]).

At baseline, the 2,451 patients had a mean age of 56 years, HbA1c of 7.6 percent, and a median duration of type 2 diabetes of five years. Baseline characteristics were similar between the two treatment groups. The cumulative patient exposure was 1,269 patient-years in the sitagliptin group and 1,274 patient-years in the SU group.

Incidence of CV-Related Events with sitagliptin Versus SU in Patients with Type 2 Diabetes

In this pooled analysis, the incidence rate for reported MACE events was 0 per 100 patient years in the sitagliptin group (0 events) and 0.9 per 100 patient years in the SU group (11 events, between-group difference [95% CI] = -0.9 [-1.6, -0.5]). For CV-related death, the incidence rate was 0 per 100 patient-years (0 deaths) with sitagliptin, and 0.4 per 100 patient years (5 deaths) in the SU group (-0.4 [-0.9, -0.1]).

JANUVIA is indicated as an adjunct to diet and exercise to improve glycemic control in patients with type 2 diabetes mellitus as initial therapy, alone or in combination with metformin, or a PPAR? agonist, or as an add-on to metformin, PPAR? agonist, sulphonylurea, sulphonylurea + metformin or PPAR? agonist + metformin when the current regimen, with diet and exercise does not provide adequate glycemic control. The medication can also be used as an adjunct to diet and exercise to improve glycemic control in combination with insulin (with or without metformin).

Important selected safety information about JANUVIA

JANUVIA is contraindicated in patients who are hypersensitive to any components of this product. JANUVIA should not be used in patients with type 1 diabetes or for the treatment of diabetic ketoacidosis.

There have been postmarketing reports of acute pancreatitis, including fatal and non-fatal hemorrhagic or necrotizing pancreatitis, in patients taking JANUVIA. Because these reports are made voluntarily from a population of uncertain size, it is generally not possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Patients should be informed of the characteristic symptom of acute pancreatitis: persistent, severe abdominal pain. Resolution of pancreatitis has been observed after discontinuation of JANUVIA. If pancreatitis is suspected, JANUVIA and other potentially suspect medicinal products should be discontinued.

As the experience is limited, patients with moderate to severe renal impairment should not be treated with JANUVIA. JANUVIA is not recommended for use in children below 18 years of age due to a lack of data on its safety and efficacy. JANUVIA should not be used during pregnancy or during breast-feeding.

As with other antihyperglycemic agents, when JANUVIA was used in combination with a sulphonylurea or with insulin, medications known to cause hypoglycemia, the incidence of sulphonylurea- or insulin-induced hypoglycemia was increased over that of placebo. To reduce the risk of sulphonylurea- or insulin-induced hypoglycemia, a lower dose of sulphonylurea or insulin may be considered.

There have been postmarketing reports of serious hypersensitivity reactions in patients treated with JANUVIA including anaphylaxis, angioedema, and exfoliative skin conditions including Stevens-Johnson syndrome. Because these reactions are reported voluntarily from a population of uncertain size, it is generally not possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Onset of these reactions occurred within the first three 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.

In clinical studies as monotherapy and in combination with other agents, the adverse experiences reported regardless of causality assessment in >5 percent of patients and more commonly than placebo or the active comparator included hypoglycemia, nasopharyngitis, upper respiratory tract infection, headache, and peripheral edema. For additional adverse experience information, see the product circular.

Before initiating therapy, please consult the full prescribing information

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