WARNING FOR KOMBIGLYZE XR: LACTIC ACIDOSIS
US Full Prescribing Information including Boxed WARNING about lactic acidosis, and Medication Guide
Lactic acidosis is a rare, but serious, complication that can occur due to metformin accumulation. The risk increases with conditions such as sepsis, dehydration, excess alcohol intake, hepatic impairment, renal impairment, and acute congestive heart failure.
The onset of lactic acidosis is often subtle, accompanied only by nonspecific symptoms such as malaise, myalgias, respiratory distress, increasing somnolence, and nonspecific abdominal distress.
Laboratory abnormalities include low pH, increased anion gap, and elevated blood lactate.
If acidosis is suspected, KOMBIGLYZE™ XR (saxagliptin and metformin HCl extended-release) should be discontinued and the patient hospitalized immediately. [See Warnings and Precautions]
Click here for Important Safety Information including complete Boxed WARNING about lactic acidosis
A TREATMENT FOR ADULTS WITH TYPE 2 DIABETES MELLITUS, IN ADDITION TO DIET AND EXERCISE
Saxagliptin 5 mg + metformin IR provided statistically significant reductions in A1C levels vs placebo + metformin IR at 6 months1,2,a,b
(95% Cl: -1.0%, -0.6%)
GREATER REDUCTION WITH SAXAGLIPTIN 5 MG + METFORMIN IR
GREATER REDUCTION WITH SAXAGLIPTIN 5 MG + METFORMIN IR
-0.8%
(95% Cl: -1.0%, -0.6%)
P<0.0001 vs placebo + metformin IR.
aIn these studies, saxagliptin 5 mg and metformin IR were administered as separate tablets.
bIntent-to-treat population using last observation on study or last observation prior to pioglitazone rescue therapy for patients needing rescue.
Uncontrolled on Metformin Monotherapy
Saxagliptin 5 mg + metformin IR delivered statistically significant reductions in fasting plasma glucose (FPG) and postprandial glucose (PPG) vs placebo + metformin IR at 6 months1,2,c,d
GREATER REDUCTIONS WITH SAXAGLIPTIN 5 MG + METFORMIN IR
FPG
-23 mg/dL
(95% Cl: -30 mg/dL, -16 mg/dL)
GREATER REDUCTIONS WITH SAXAGLIPTIN 5 MG + METFORMIN IR
2-HOUR PPG
-40 mg/dL
(95% Cl: -56 mg/dL, -24 mg/dL)
FPG
-23 mg/dL(95% Cl: -30 mg/dL, -16 mg/dL)
2-HOUR PPG
-40 mg/dL(95% Cl: -56 mg/dL, -24 mg/dL)
P<0.05 vs placebo + metformin IR.
cIn these studies, saxagliptin 5 mg and metformin IR were administered as separate tablets.
dIntent-to-treat population using last observation on study or last observation prior to pioglitazone rescue therapy for patients needing rescue.
Phase 3, 24-week, multicenter, randomized, double-blind, placebo-controlled study
A1C ≥7.0% and ≤10.0% (n=743)
*Metformin IR dose was between 1500 and 2500 mg daily.
Evaluate the efficacy and safety of saxagliptin, in addition to diet and exercise, as add-on to metformin IR compared to placebo + metformin IR.
A1C change from baseline at 6 months
6 months
6 months
Demographic: Men and women age 18–77 years
Diagnosis: Type 2 diabetes mellitus (T2DM)
A1C: ≥7.0% and ≤10.0%
Metformin Dose: Stable monotherapy ≥1500 mg/day but not >2550 mg/day for at least 8 weeks prior to enrollment
Fasting C-peptide: ≥1.0 ng/mL
Body Mass Index: ≤40 kg/m2
After the lead-in period, eligible patients were randomly assigned 1:1:1:1 (permuted blocks stratified by site) by an interactive voice response system to 2.5, 5, or 10 mg saxagliptin or placebo for 24 weeks in addition to their lead-in dose of open-label metformin.
A1C change from baseline at 6 months
A1C change from baseline at 6 months