Effect of Sitagliptin on Short-Term Metabolic Dysregulation of Oral Glucocorticoid Therapy
Condition: Pre-diabetes; Impaired Fasting Glucose; Impaired Glucose Tolerance
MeSH terms: Prediabetic State; Glucose Intolerance
Study type: Interventional

Summary: 
      The investigators hypothesize that sitagliptin will significantly reduce impairments in
      insulin secretion and insulin resistance resulting from short-term oral glucocorticoid
      therapy.
    

Detailed description: 
      The investigators plan to conduct a prospective, randomized, double-blind, placebo-controlled
      parallel arm crossover study comparing insulin secretion and insulin resistance in subjects
      with impaired fasting glucose on oral glucocorticoid therapy + placebo versus subjects on
      oral glucocorticoid therapy + sitagliptin. For the oral glucocorticoid therapy, we plan to
      use dexamethasone (dex) 2.5 mg daily. We chose dex for known glycemic effects, improved
      compliance, and once daily dosing.

      Previous studies have shown that in humans, glucocorticoid-induced insulin resistance
      develops within 4 hours with infused drug at high dose (methylprednisolone 500 mg x single
      infusion) and does not change with duration of drug therapy of up to 3 months.10 Furthermore,
      more modest doses over a short duration (dex 2.0 mg orally daily x 2 days) have been shown to
      decrease insulin-mediated glucose disposal.11 12 Thus, studying acute effects of oral dex at
      2.5 mg daily x 7 days should be more than adequate to achieve impaired glucose-mediated
      insulin secretion and impaired insulin-mediated glucose disposal.

      In order for sitagliptin to have the desired effect, drug should be administered for at least
      7 days (5 half-lives plus 40% more for margin of error). We plan to study subjects with
      impaired fasting glucose or impaired glucose tolerance as they would likely be candidates for
      DPP-IV therapy in the future and would be likely to have impaired insulin secretion and
      impaired glucose disposal amenable to DPP-IV therapy.

      A total of 10 participants were enrolled in this study. Participants were given 2.5 mg
      dexamethasone daily plus either placebo tablet or sitagliptin daily for 8 days with a washout
      period prior to crossover. The order of study drug administration was randomized.
      Participants underwent blood sampling, mixed meal testing (MMT), and intravenous glucose
      tolerance testing (IVGTT) before and after each study period.
    

Intervention name(s): Dexamethasone 2.5 mg and Sitagliptin 100 mg; Dexamethasone 2.5 mg and placebo tablet
Intervention type(s): Drug; Drug
Intervention description(s): Participants received Dexamethasone 2.5mg plus Sitaliptin 100mg daily for 8 days; Participants rececived Dexamethasone 2.5 mg plus placebo tablet daily for 8 days
Other intervention name(s): Sitagliptin; Placebo
Intervention MeSH terms: Sitagliptin Phosphate; Dexamethasone; Dexamethasone acetate; BB 1101
Allocation: Randomized
Intervention model: Crossover Assignment
Intervention model description: Double blind, placebo controlled crossover study
Masking: Double (Participant, Investigator)
Primary purpose: Treatment
Keywords: Pre-diabetes; Impaired fasting glucose; Impaired glucose tolerance; Steroid-induced hyperglycemia