WARNING: LACTIC ACIDOSIS
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 should be discontinued and the patient hospitalized immediately. [See
Warnings and Precautions
KOMBIGLYZE XR (saxagliptin and metformin HCl extended-release)
tablets contain two oral antihyperglycemic medications used in the management of
type 2 diabetes: saxagliptin and metformin hydrochloride.
KOMBIGLYZE XR is indicated as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes mellitus when treatment with both saxagliptin and metformin is appropriate.
[See Clinical Studies]
Important Limitations of Use
KOMBIGLYZE XR should not be used for the treatment of type 1 diabetes mellitus or diabetic ketoacidosis.
KOMBIGLYZE XR has not been studied in patients with a history of pancreatitis. It is unknown whether patients with a history of pancreatitis are at an increased risk for the development of pancreatitis while using KOMBIGLYZE XR. [See Warnings and Precautions]
Published Studies Related to Kombiglyze (Saxagliptin / Metformin)
Bioequivalence of saxagliptin/metformin extended-release (XR) fixed-dose combination tablets and single-component saxagliptin and metformin XR tablets in healthy adult subjects. 
BACKGROUND AND OBJECTIVES: As compared with individual tablets, saxagliptin/metformin extended-release (XR) fixed-dose combination (FDC) tablets offer potential for increased patient compliance with the convenience of once-daily dosing. Two bioequivalence studies assessed the fed-state bioequivalence of saxagliptin/metformin XR 5 mg/500 mg FDC (study 1) and saxagliptin/metformin XR 5 mg/1000 mg FDC (study 2) relative to the same dosage strengths of individual component tablets administered concurrently. The effect of food on saxagliptin and metformin pharmacokinetics from the saxagliptin/metformin XR 5 mg/500 mg FDC and their steady-state pharmacokinetics from the saxagliptin/metformin XR 5 mg/1000 mg were also investigated... CONCLUSION: Saxagliptin/metformin XR 5 mg/500 mg and saxagliptin/metformin XR 5 mg/1000 mg FDCs were bioequivalent to individual tablets of saxagliptin and metformin of the same strengths. Additionally, food had little effect on the pharmacokinetics of saxagliptin and metformin administered in the saxagliptin/metformin XR 5 mg/500 mg FDC and the steady-state pharmacokinetics of the saxagliptin/metformin XR 5 mg/1000 mg FDC was consistent over time. No unexpected safety findings were observed with saxagliptin/metformin XR administration. The tolerability of the FDC of saxagliptin/metformin XR was comparable to that of the co-administered individual components. These results indicate that the safety and efficacy profile of co-administration of saxagliptin and metformin can be extended to the saxagliptin/metformin XR FDC tablets. TRIALS REGISTRATION: ClinicalTrials.gov Identifiers: NCT01192139 and NCT01192152.
Clinical Trials Related to Kombiglyze (Saxagliptin / Metformin)
Saxagliptin + Metformin Compared to Saxagliptin or Metformin Monotherapy in PCOS Women With Impaired Glucose Homeostasis [Recruiting]
The objective of the present proposal is to compare the clinical, endocrine and metabolic
effects of therapy with combination saxagliptin and metformin to saxagliptin and metformin
monotherapy in women with PCOS and prediabetic hyperglycemia (IFG, IGT or IFG/IGT).
Saxagliptin is an oral dipeptidyl peptidase IV (DPP-4) inhibitor whose mechanism of action
is to prolong the duration of blood glucagon-like peptide (GLP-1) and glucose-dependent
insulinotropic polypeptide (GIP) levels by inhibiting their degradation and thereby
augmenting insulin secretion. This study will serve as a pilot investigation to open
perspectives for future studies to explore the potential of combining anti-diabetic drugs
with different mechanisms of action in in patients with PCOS and impaired glucose regulation
(IGR), especially ones for whom standard treatment with metformin is less effective.