title: Long-term efficacy of sitagliptin as either monotherapy or add-on therapy to metformin: improvement in glycemic control over 2 years in patients with type 2 diabetes.
abstract: OBJECTIVE
  To evaluate the efficacy of once daily sitagliptin 100 mg as monotherapy or as add-on to metformin in patients with type 2 diabetes mellitus (T2DM) over 2 years of treatment.
  
  
  METHODS
  The monotherapy analysis used pooled 104 week data from 64 patients in two randomized, double-blind trials evaluating the safety and efficacy of sitagliptin monotherapy. Data used were from patients who were randomized to sitagliptin 100 mg/day, were not on an antihyperglycemic agent at the screening visit, had baseline A1C of 7.0%-10.0%, and had Week 104 A1C measurements. The add-on to metformin analysis used pooled data from 347 patients in two randomized double-blind trials evaluating the safety and efficacy of sitagliptin + metformin combination therapy. Data used were from patients who were randomized to sitagliptin 100 mg/day + metformin ≥1500 mg/day, had baseline A1C of 7%-10%, and had Week 104 A1C measurements. Excluded from either analysis were patients who discontinued prior to 2 years (e.g., due to lack of efficacy, a need for rescue medications, or adverse experiences). Analysis endpoints were A1C, fasting plasma glucose (FPG), HOMA-β, proinsulin/insulin (P/I) ratio, and for monotherapy, 2 hour post-meal plasma glucose (PMG).
  
  
  RESULTS
  For the pooled monotherapy cohort, after 2 years of treatment, mean A1C, FPG, and 2 hour PMG decreased from baseline values of 7.9%, 156 mg/dL, and 223 mg/dL to 6.9%, 143 mg/dL, and 191 mg/dL, respectively, while HOMA-β increased from 67% to 85% and P/I ratio improved from 0.57 to 0.28. For the pooled add-on to metformin cohort, after 2 years of treatment, mean A1C and FPG decreased from baseline values of 7.7% and 160 mg/dL to 6.9% and 140 mg/dL, respectively, while HOMA-β increased from 50% to 62% and P/I ratio improved from 0.33 to 0.28. These analyses are limited in that only patients who were able to complete 104 weeks of study were included.
  
  
  CONCLUSIONS
  In the subset of patients with T2DM who maintained and completed treatment for 2 years with sitagliptin as monotherapy or as add-on to metformin, improvements in glycemic control and measures of β-cell function were observed over the course of treatment.
authors: Merck & Co. Inc., Kenilworth , NJ , USA.
authors: H L
authors: HL
authors: Katzeff
authors: D
authors: D
authors: Williams-Herman
authors: L
authors: L
authors: Xu
authors: G T
authors: GT
authors: Golm
authors: H
authors: H
authors: Wang
authors: Q
authors: Q
authors: Dong
authors: J R
authors: JR
authors: Johnson
authors: E A
authors: EA
authors: O'Neill
authors: K D
authors: KD
authors: Kaufman
authors: S S
authors: SS
authors: Engel
authors: B J
authors: BJ
authors: Goldstein
mesh_terms: D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D050417:Insulin-Secreting Cells / Q000378:metabolism; D008297:Male; D008687:Metformin / Q000008:administration & dosage*; D008875:Middle Aged; D019518:Postprandial Period; D000068900:Sitagliptin Phosphate / Q000008:administration & dosage* / Q000627:therapeutic use
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D008687:Metformin; D000068900:Sitagliptin Phosphate
keywords: Beta-cell function; DPP-4; HOMA-β; Incretins; P/I ratio; Type 2 diabetes disease progression