Effect of Omeprazole on Metformin
Condition: Healthy
Study type: Interventional
Phase: Phase 1

Summary: 
      In this study, investigators hypothesized that the plasma concentration of metformin and its
      glucose-lowering action would be affected by omeprazole, probably by altering the expression
      or function of OCTs in the liver, its primary target organ, as well as in the kidney.
    

Detailed description: 
      Metformin is the most widely used drug for the treatment of type 2 diabetes. This
      insulin-sensitizing agent has well known beneficial effects not only on glycemic control, but
      also on the cardiovascular system. The antihyperglycemic effect of metformin is mainly based
      on suppression of hepatic gluconeogenesis by activation of AMP-activated protein kinase
      (AMPK), which suppresses glucagon-stimulated glucose production and causes an increase in
      glucose uptake in muscle and in hepatic cells. Metformin is actively transported across
      membranes. The organic cation transporter 1 (OCT1) is responsible for uptake of metformin in
      hepatocytes, which is an essential step in reducing hepatic glucose production. , which is
      closely associated with its pharmacological action/adverse reactions.

      However, metformin alone is thought to be insufficient for achieving good metabolic control.
      Thus, treatment in addition to metformin is often required. Sitagliptin attenuates
      metformin-mediated AMPK phosphorylation through inhibition of organic cation transporters
      PPIs are frequently used in metformin-treated patients with metabolic syndrome and
      cardiovascular diseases. Moreover, gastroesophageal reflux disease (GERD) is commonly seen in
      patients with type 2 diabetes and proton-pump inhibitors (PPIs) are the drugs of best choice
      in treatment of GERD. These data support the hypothesis that proton pump inhibitors can be
      used to treat type II diabetes. Moreover, PPIs itself appears to has significant
      glucose-lowering effects in an animal model of type 2 diabetes regardless of whether
      metformin is administered concurrently.

      A recent in-vitro study found that PPI inhibit metformin uptake by organic cation
      transporters (OCTs). This drug-drug interaction the clinical has the potential relevance of
      consequences on metformin disposition and/or efficacy. Since there is a possibility for the
      combined use of metformin and omeprazole in chronic diabetics, the study is planned to
      investigate the effect of nicorandil on the activity of gliclazide in normal and diabetic
      rats to evaluate effectiveness of the combination.

      The study is planned to find the pharmacodynamics and pharmacokinetics of metformin in the
      presence of omeprazole in healthy subjects and to evaluate the mechanisms of the interaction
      if occurs.
    

Intervention name(s): Placebo; Omeprazole
Intervention type(s): Drug; Drug
Other intervention name(s): PPI
Intervention MeSH terms: Omeprazole
Allocation: Randomized
Intervention model: Crossover Assignment
Masking: Single (Participant)
Primary purpose: Treatment
Keywords: Omeprazole; Metformin