title: A Randomized Clinical Trial to Evaluate the Efficacy and Safety of Co-Administration of Sitagliptin with Intensively Titrated Insulin Glargine.
abstract: BACKGROUND
  The objective of this study was to assess the effect of sitagliptin on insulin dose in patients with inadequately controlled type 2 diabetes who titrate basal insulin to a target fasting glucose level after initiating sitagliptin.
  
  
  METHODS
  This was a multicenter, randomized, double-blind, placebo-controlled, 24-week clinical trial in which treatment with sitagliptin 100 mg/day or placebo was administered concurrently with insulin glargine titration, targeting a fasting glucose of 4.0-5.6 mmol/L (72-100 mg/dL). The trial randomized 660 patients with type 2 diabetes and inadequate glycemic control on insulin, with or without metformin (≥1500 mg/day) or sulfonylurea, for ≥10 weeks. Patients could remain on metformin but not sulfonylurea after randomization.
  
  
  RESULTS
  The increase from baseline in the daily dose of insulin was less in the sitagliptin group (N = 329) compared to placebo (N = 329) (between group difference = -4.7 IU [95% confidence interval [CI] -8.3, -1.2]; p = 0.009). Patients in the sitagliptin group had lower glycated hemoglobin (HbA1c) levels after 24 weeks (between-group difference of -0.4% [95% CI -0.6, -0.3; -4.9 mmol/mol (95% CI -6.6, -3.2)]; p < 0.001), and more patients in the sitagliptin group reached the HbA1c goal of <7.0% (53 mmol/mol), with a between-group difference of 17.3% (95% CI 10.4%, 24.1%; p < 0.001). Fewer patients in the sitagliptin group experienced an adverse event of hypoglycemia (between-group difference = -15.5%, p < 0.001).
  
  
  CONCLUSIONS
  Administration of sitagliptin prior to intensive titration of basal insulin glargine reduces the insulin dose requirement while providing superior glycemic control and less hypoglycemia, compared to an insulin-only regimen.
  
  
  BACKGROUND
  Merck & Co., Inc., Kenilworth, NJ, USA.
authors.affiliation: Clinical and Experimental Endocrinology, KU Leuven, Leuven, Belgium.
authors.forename: Chantal
authors.initials: C
authors.lastname: Mathieu
authors.forename: R Ravi
authors.initials: RR
authors.lastname: Shankar
authors.forename: Daniel
authors.initials: D
authors.lastname: Lorber
authors.forename: Guillermo
authors.initials: G
authors.lastname: Umpierrez
authors.forename: Fan
authors.initials: F
authors.lastname: Wu
authors.forename: Lei
authors.initials: L
authors.lastname: Xu
authors.forename: Gregory T
authors.initials: GT
authors.lastname: Golm
authors.forename: Melanie
authors.initials: M
authors.lastname: Latham
authors.forename: Keith D
authors.initials: KD
authors.lastname: Kaufman
authors.forename: Samuel S
authors.initials: SS
authors.lastname: Engel
references.citation: Diabetes Care. 2011 Aug;34(8):1723-8
references.pmid: 21700919
references.citation: Diabetes. 2006 Apr;55(4):1114-20
references.pmid: 16567536
references.citation: N Engl J Med. 1998 Mar 26;338(13):861-6
references.pmid: 9516220
references.citation: Diabetes Obes Metab. 2012 May;14(5):433-46
references.pmid: 22142056
references.citation: Diabetes Care. 2006 Dec;29(12):2638-43
references.pmid: 17130197
references.citation: Diabetes Obes Metab. 2014 Sep;16(9):812-8
references.pmid: 24612221
references.citation: Postgrad Med. 2014 Oct;126(6):93-105
references.pmid: 25414938
references.citation: Curr Med Res Opin. 2012 Apr;28(4):513-23
references.pmid: 22313154
references.citation: Clin Ther. 2006 Oct;28(10):1556-68
references.pmid: 17157112
references.citation: Diabetes Care. 2013 Dec;36(12):3875-81
references.pmid: 24062327
references.citation: Diabetes Care. 2012 Jun;35(6):1364-79
references.pmid: 22517736
references.citation: Prim Care Diabetes. 2015 Oct;9(5):370-6
references.pmid: 25488587
references.citation: Int J Clin Pract. 2002 May;56(4):251-7
references.pmid: 12074206
references.citation: Diabetes Care. 2003 Nov;26(11):3080-6
references.pmid: 14578243
references.citation: Diabetes Care. 1998 Jul;21(7):1052-7
references.pmid: 9653594
references.citation: Diabetes. 2011 Dec;60(12):3103-9
references.pmid: 21984584
references.citation: J Clin Invest. 1999 Sep;104(6):787-94
references.pmid: 10491414
references.citation: Diabetes Care. 2001 Jul;24(7):1226-32
references.pmid: 11423507
references.citation: Diabetes Obes Metab. 2012 Sep;14(9):795-802
references.pmid: 22443183
references.citation: Diabetes Care. 2006 Dec;29(12):2632-7
references.pmid: 17130196
references.citation: Eur J Clin Pharmacol. 1993;44(2):107-12
references.pmid: 8453955
references.citation: Diabetologia. 2006 Mar;49(3):442-51
references.pmid: 16456680
references.citation: Diabetes Care. 2005 Jun;28(6):1282-8
references.pmid: 15920040
references.citation: J Clin Endocrinol Metab. 2014 Mar;99(3):E418-26
references.pmid: 24423311
references.citation: Diabetes. 2002 Jul;51(7):2170-8
references.pmid: 12086947
references.citation: Diabetes Obes Metab. 2007 Sep;9(5):733-45
references.pmid: 17593236
references.citation: Diabetes Care. 1996 Jul;19(7):744-50
references.pmid: 8799631
references.citation: Diabetes Care. 2010 Dec;33(12):2496-501
references.pmid: 20805258
references.citation: Stat Med. 1985 Apr-Jun;4(2):213-26
references.pmid: 4023479
references.citation: Diabetologia. 2007 Jun;50(6):1148-55
references.pmid: 17387446
references.citation: Diabetes Obes Metab. 2010 Feb;12(2):167-77
references.pmid: 20092585
references.citation: Ann Intern Med. 1999 Aug 3;131(3):182-8
references.pmid: 10428734