title: Comparison between sitagliptin and nateglinide on postprandial lipid levels: The STANDARD study.
abstract: OBJECTIVE
  To assess the effects of sitagliptin and nateglinide on lipid metabolism.
  
  
  METHODS
  In a parallel group comparative open trial, patients with type 2 diabetes mellitus under treatment at the Japanese Red Cross Medical Center were randomly assigned to receive either sitagliptin (50 mg once daily) or nateglinide (90 mg three times daily before meals). Eligible patients met the following criteria: age ≥ 20 years; hemoglobin A1c (HbA1c) > 6.5% despite diet and exercise; HbA1c between 6.5% and 8.0%; fasting glucose < 7.77 mmol/L; diet and exercise therapy for more than 3 mo; and ability to read and understand the information for written informed consent. Exclusion criteria were contraindications to sitagliptin, contraindications to nateglinide, pregnancy or possible pregnancy, and severe liver/renal failure. Patients who were considered to be unsuitable by the attending physician for other reasons were also excluded. Blood samples were collected at one and three hours after intake of a test meal. The primary outcome measure was the area under the curve (AUC) of apolipoprotein (Apo) B48 at three hours postprandially.
  
  
  RESULTS
  Twenty patients were randomly assigned to the sitagliptin group and sixteen patients were randomized to the nateglinide group. All 36 patients took the medication as directed by the physician in both groups, and they all were analyzed. Apart from antidiabetic drugs, there was no difference between the two groups with respect to the frequency of combined use of lipid-lowering, antihypertensive, and/or antiplatelet drugs. The doses of these medications were maintained during 12 wk of treatment. Detailed dietary advice, together with adequate exercise therapy, was given to the patients so that other factors apart from the two test drugs were similar in the two groups. There were no significant differences of the baseline characteristics between the two groups, except for body mass index (the sitagliptin group: 25.14 ± 3.05 kg/m(2); the nateglinide group: 21.39 ± 2.24 kg/m(2)). Fasting levels of HbA1c, glycated albumin, 1.5-anhydroglucitol, and blood glucose, as well as the blood glucose levels at one and three hours postprandially, improved in both groups after 12 wk of treatment, and there were no significant differences between the two groups. However, the glucagon level at one hour postprandially (P = 0.040) and the diastolic blood pressure (P < 0.01) only showed a significant decrease in the sitagliptin group. In the nateglinide group, there was no significant change in the AUC of Apo B48, the glucagon level at one hour postprandially, the fasting triglyceride level, or the diastolic blood pressure. Body weight was unchanged in both groups. However, the AUC of Apo B48 at three hours postprandially showed a significant decrease in the sitagliptin group from 2.48 ± 0.11 at baseline to 1.94 ± 0.78 g/L per hour after 12 wk (P = 0.019). The fasting triglyceride level also decreased significantly in the sitagliptin group (P = 0.035). With regard to lipid-related markers other than Apo B48 and fasting triglycerides, no significant changes were observed with respect to Apo A1, Apo B, or Apo C3 in either group. No adverse events occurred in either group.
  
  
  CONCLUSIONS
  Sitagliptin significantly improves some lipid parameters while having a comparable effect on blood glucose to nateglinide. A large-scale prospective study of sitagliptin therapy is warranted.
authors.affiliation: Yuichi Kojima, Hideyoshi Kaga, Shinu Hayashi, Toru Kitazawa, Yuko Iimura, Makoto Ohno, Michiyasu Yoshitsugu, Mutsunori Fujiwara, Toru Hiyoshi, Japanese Red Cross Medical Center, Tokyo 150-8935, Japan.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Kojima
authors.forename: Hideyoshi
authors.initials: H
authors.lastname: Kaga
authors.forename: Shinu
authors.initials: S
authors.lastname: Hayashi
authors.forename: Toru
authors.initials: T
authors.lastname: Kitazawa
authors.forename: Yuko
authors.initials: Y
authors.lastname: Iimura
authors.forename: Makoto
authors.initials: M
authors.lastname: Ohno
authors.forename: Michiyasu
authors.initials: M
authors.lastname: Yoshitsugu
authors.forename: Mutsunori
authors.initials: M
authors.lastname: Fujiwara
authors.forename: Toru
authors.initials: T
authors.lastname: Hiyoshi
keywords: Blood glucose; Dipeptidyl-peptidase 4 inhibitors; Lipid metabolism; Nateglinide; Sitagliptin; Type 2 diabetes mellitus