The PI Summary below is taken from a BMS Press Release July 31 2009
ONGLYZA Complements Metformin to Provide Statistically Significant A1C Reductions
ONGLYZA was studied extensively with metformin, the most commonly-prescribed oral anti-diabetic medication. In adult patients inadequately controlled on metformin, the addition of ONGLYZA 2.5 mg (n=192, baseline A1C 8.1 percent) and 5 mg (n=191, baseline A1C 8.1 percent) once daily reduced A1C levels from baseline to Week 24 by -0.6 percent and –0.7 percent respectively for ONGLYZA™ (saxagliptin) vs. +0.1 percent increase for placebo (p<0.0001 vs. placebo, n=179, baseline A1C 8.1 percent). The reported incidence of hypoglycemia in ONGLYZA 2.5 mg and 5 mg compared with placebo was 7.8 percent, 5.8 percent and 5 percent, respectively.
For those new to diabetes medications, the use of ONGLYZA 5 mg with metformin (n=320, baseline A1C 9.4 percent) as initial therapy lowered A1C from baseline to week 24 by -2.5 percent vs. -2 percent for metformin plus placebo (p<0.0001, n=313, baseline A1C 9.4 percent). Significantly more adult patients in the ONGLYZA plus metformin arm achieved the American Diabetes Association recommended A1C level of less than 7 percent than those treated with metformin plus placebo (60 percent vs. 41 percent, respectively, p<0.05). The reported incidence of hypoglycemia was 3.4 percent in adult patients given ONGLYZA 5 mg plus metformin and 4 percent in adult patients given metformin alone. The adverse reactions occurring in ≥5 percent of adult patients and more commonly than in adult patients treated with metformin alone were headache (7.5 percent vs. 5.2 percent) and nasopharyngitis (6.9 percent vs. 4 percent).
Complementary and Statistically Significant A1C Reductions When Added to the Sulfonylurea Glyburide or TZDs
ONGLYZA also offered better glucose control for adult patients currently uncontrolled on glyburide. The addition of ONGLYZA 2.5 mg (n=248, baseline A1C 8.4 percent) or 5 mg (n=253, baseline A1C 8.5 percent) to a submaximal total daily dose of glyburide 7.5 mg reduced A1C levels from baseline at week 24 by -0.5 percent and -0.6 percent, respectively for ONGLYZA vs. +0.1 percent increase with an approximate doubling of the total daily dose of the glyburide plus placebo (p<0.0001 vs. uptitrated glyburide, n=267, baseline A1C 8.4 percent). The reported incidence of hypoglycemia for ONGLYZA 2.5 mg or 5 mg compared with the high-dose glyburide group was 13.3 percent and 14.6 percent vs. 10.1 percent, respectively. Confirmed hypoglycemia was 2.4 percent, 0.8 percent and 0.7 percent, respectively (defined as symptoms of hypoglycemia accompanied by a fingerstick glucose value of ≤50 mg/dL). When used with a sulfonylurea, a lower dose of the sulfonylurea may be required to reduce the risk of hypoglycemia.
When used in addition to TZDs (pioglitazone or rosiglitazone), ONGLYZA™ (saxagliptin) offered additional glucose control. The addition of ONGLYZA 2.5 mg (n=195, baseline A1C 8.3 percent) and 5 mg (n=186, baseline A1C 8.4 percent) reduced A1C levels from baseline at week 24 by -0.7 percent and -0.9 percent, respectively vs. –0.3 percent for placebo (p<0.05 vs. placebo, n=184, baseline A1C 8.2 percent). The reported incidence of hypoglycemia with ONGLYZA 2.5 mg and 5 mg compared with placebo was 4.1 percent and 2.7 percent vs. 3.8 percent, respectively. The incidence of peripheral edema was 3.1 percent and 8.1 percent vs. 4.3 percent as compared to placebo; none resulted in discontinuation of therapy.
ONGLYZA Provides Significant A1C Reduction When Used as Monotherapy
When studied as a monotherapy, ONGLYZA significantly improved glucose control, with a difference in A1C from baseline of -0.4 percent and -0.5 percent for ONGLYZA 2.5 mg (n=102, baseline A1C 7.9 percent) and 5 mg (n=106, baseline A1C 8.0 percent), respectively, vs. +0.2 percent increase for placebo (p<0.0001 vs. placebo, n=95, baseline A1C 7.9 percent) at Week 24. The reported incidence of hypoglycemia in the ONGLYZA groups compared with placebo given as monotherapy was 4 percent and 5.6 percent vs. 4.1 percent, respectively.
ONGLYZA had an Overall Incidence of Side Effects Similar to Placebo
In clinical trials, the overall incidence of side effects for ONGLYZA 2.5 mg and 5 mg was similar to placebo (72 percent and 72.2 percent vs. 70.6 percent, respectively). The most common events reported with ONGLYZA 5 mg (≥5 percent and more commonly than placebo) were upper respiratory tract infection (7.7 percent vs. 7.6 percent, respectively), urinary tract infection (6.8 percent vs. 6.1 percent, respectively) and headache (6.5 percent vs. 5.9 percent, respectively). In adult patients treated with ONGLYZA 2.5 mg, only headache (6.5 percent) was reported at ≥5 percent and more commonly than in adult patients treated with placebo. Discontinuation of therapy due to adverse events occurred in 2.2 percent, 3.3 percent, and 1.8 percent of patients receiving ONGLYZA 2.5 mg, ONGLYZA 5 mg, and placebo, respectively. There was a dose-related mean decrease in absolute lymphocyte count observed with ONGLYZA.
ONGLYZA™ (saxagliptin) Offers Convenient Once Daily Dosing
ONGLYZA offers convenient, once-daily dosing of 2.5 mg or 5 mg that can be taken regardless of meals.
ONGLYZA 2.5 mg is recommended for adult patients with moderate or severe renal impairment, or end-stage renal disease requiring hemodialysis (creatinine clearance less ≤50 mL/min). ONGLYZA has not been studied in patients undergoing peritoneal dialysis. Assessment of renal function is recommended prior to initiation of ONGLYZA and periodically thereafter.
The dose for ONGLYZA should be limited to 2.5 mg when coadministered with strong cytochrome P450 3A4/5 (CYP 3A4/5) inhibitors (e.g., ketoconazole).
No dose adjustment is required based on gender, race, weight or hepatic impairment.
IMPORTANT INFORMATION ABOUT ONGLYZA
Indication and Important Limitations of Use
ONGLYZA is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus.
ONGLYZA should not be used for the treatment of type 1 diabetes mellitus or diabetic ketoacidosis.
ONGLYZA has not been studied in combination with insulin.
Important Safety Information
Most common adverse reactions (regardless of investigator assessment of causality) reported in ≥5 percent of patients treated with ONGLYZA and more commonly than in patients treated with control were upper respiratory tract infection (7.7 percent, 7.6 percent), headache (7.5 percent, 5.2 percent), nasopharyngitis (6.9 percent, 4.0 percent) and urinary tract infection (6.8 percent, 6.1 percent). When used as add-on combination therapy with a thiazolidinedione, the incidence of peripheral edema for ONGLYZA 2.5 mg, 5 mg, and placebo was 3.1 percent, 8.1 percent and 4.3 percent, respectively.
Drug Interactions: Because ketoconazole, a strong CYP 3A4/5 inhibitor, increased saxagliptin exposure, the dose of ONGLYZA should be limited to 2.5 mg when coadministered with a strong CYP 3A4/5 inhibitor (e.g., atazanavir, clarithromycin, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, saquinavir, and telithromycin).
Patients with Renal Impairment: The dose of ONGLYZA is 2.5 mg once daily for patients with moderate or severe renal impairment, or with end-stage renal disease requiring hemodialysis (creatinine clearance ≤50 mL/min). ONGLYZA should be administered following hemodialysis. ONGLYZA has not been studied in patients undergoing peritoneal dialysis. Assessment of renal function is recommended prior to initiation of ONGLYZA and periodically thereafter.
Pregnant and Nursing Women: There are no adequate and well-controlled studies in pregnant women. ONGLYZA, like other antidiabetic medications, should be used during pregnancy only if clearly needed. It is not known whether saxagliptin is secreted in human milk. Because many drugs are secreted in human milk, caution should be exercised when ONGLYZA is administered to a nursing woman.
Pediatric Patients: Safety and effectiveness of ONGLYZA™ (saxagliptin) in pediatric patients have not been established.
Please see accompanying US Full Prescribing Information or visit www.bms.com.