Safety and Efficacy of Sitagliptin Therapy for the Inpatient Management of General Medicine and Surgery Patients With Type 2 Diabetes A pilot, randomized, controlled study Guillermo Umpierrez, Emory University David Reyes, Emory University Sangeeta Lathkar-Pradhan, University of Michigan Health System Francisco Pasquel, Emory University Roma Gianchandani, University of Michigan Health System Dawn Smiley, Emory University Sol Jacobs, Emory University David H. Wesorick, University of Michigan Health System Christopher Newton, Emory University Farnoosh Farrokhi, Emory University Only first 10 authors above; see publication for full author list. Journal Title: Diabetes Care Volume: Volume 36, Number 11 Publisher: American Diabetes Association | 2013-11-01, Pages 3430-3435 Type of Work: Article | Final Publisher PDF Publisher DOI: 10.2337/dc13-0277 Permanent URL: https://pid.emory.edu/ark:/25593/mrb19 Final published version: http://dx.doi.org/10.2337/dc13-0277 Copyright information: © 2013 by the American Diabetes Association. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommerical-NoDerivs 3.0 Unported License ( http://creativecommons.org/licenses/by-nc-nd/3.0/), which permits distribution, public display, and publicly performance, making multiple copies, provided the original work is properly cited. This license requires copyright and license notices be kept intact, credit be given to copyright holder and/or author. This license prohibits exercising rights for commercial purposes. Accessed September 23, 2021 12:53 PM EDT Clinical Care/Education/Nutrition/Psychosocial Research ORIGINAL ARTICLE Safety and Efficacy of Sitagliptin Therapy for the Inpatient Management of General Medicine and Surgery Patients With Type 2 Diabetes A pilot, randomized, controlled study 1 1 GUILLERMO E. UMPIERREZ, MD FARNOOSH FARROKHI, MD Scheduled basal bolus insulin therapy us- 2 3 ROMA GIANCHANDANI, MD LIMIN PENG, PHD 1 1 ing long- or intermediate-acting insulin DAWN SMILEY, MD DAVID REYES, MD 1 2 preparations in combination with short- SOL JACOBS, MD SANGEETA LATHKAR-PRADHAN, MBBS 2 1 (regular) or rapid-acting insulin analogs DAVID H. WESORICK, MD FRANCISCO PASQUEL, MD 1 has been proven to be safe and effective CHRISTOPHER NEWTON, MD for glycemic management in patients with diabetes or hyperglycemia (10–12). Re- cent studies in general medicine and sur- OBJECTIVEdThis study investigated the safety and efficacy of sitagliptin (Januvia) for the inpatient management of type 2 diabetes (T2D) in general medicine and surgery patients. gery patients with T2D have reported both improved glycemic control and re- RESEARCH DESIGN AND METHODSdIn this pilot, multicenter, open-label, random- ductions in a composite of hospital com- ized study, patients (n = 90) with a known history of T2D treated with diet, oral antidiabetic plications, including wound infections, agents, or low total daily dose of insulin (#0.4 units/kg/day) were randomized to receive pneumonia, bacteremia, and acute renal sitagliptin alone or in combination with glargine insulin (glargine) or to a basal bolus insulin and respiratory failure, using basal bolus regimen (glargine and lispro) plus supplemental (correction) doses of lispro. Major study out- insulin regimens when compared with comes included differences in daily blood glucose (BG), frequency of treatment failures (defined – as three or more consecutive BG .240 mg/dL or a mean daily BG .240 mg/dL), and hypogly- sliding scale insulin alone (11 14). Basal cemia between groups. bolus regimens, however, are labor inten- sive, require multiple insulin injections, RESULTSdGlycemic control improved similarly in all treatment groups. There were no dif- and are associated with a significant risk ferences in the mean daily BG after the 1st day of treatment (P = 0.23), number of readings of hypoglycemia. The rate of hypoglyce- within a BG target of 70 and 140 mg/dL (P = 0.53), number of BG readings .200 mg/dL (P = mia in non-ICU patients with T2D treated 0.23), and number of treatment failures (P . 0.99). The total daily insulin dose and number of fi with basal bolus insulin regimens has been insulin injections were signi cantly less in the sitagliptin groups compared with the basal bolus reported to be up to 32% (12,14–16). group (both P , 0.001). There were no differences in length of hospital stay (P = 0.78) or in the number of hypoglycemic events between groups (P = 0.86). Current practice guidelines recom- mend against inpatient use of oral antidi- CONCLUSIONSdResults of this pilot indicate that treatment with sitagliptin alone or in abetic drugs and noninsulin injectable combination with basal insulin is safe and effective for the management of hyperglycemia in medications in part due to the absence general medicine and surgery patients with T2D. of efficacy studies as well as safety con- cerns (7,8,10). A major limitation to using – Diabetes Care 36:3430 3435, 2013 oral antidiabetic agents in the inpatient setting relates to the delay and unpredict- ncreasing evidence from observational complications (1–6). Recent guidelines able onset of action of these drugs, which Iand randomized controlled studies in from professional organizations (7–10) can prevent rapid attainment of glycemic general medicine and surgery patients recommend the use of subcutaneous in- control or dose adjustments to meet the show that type 2 diabetes (T2D) is asso- sulin as the preferred therapy for glycemic changing needs of the acutely ill patient. ciated with prolonged hospital stay and control in hospitalized patients in a non– There is also concern regarding the poten- increased incidence of infections and hospital intensive-care unit (non-ICU) setting. tial for adverse cardiovascular effects with the use of sulfonylureas in patients with ccccccccccccccccccccccccccccccccccccccccccccccccc cardiac and cerebral ischemia (17) and From the 1Department of Medicine, Emory University School of Medicine, Atlanta, Georgia; the 2Department with the safety of metformin in patients of Internal Medicine, University of Michigan Health System, Ann Arbor, Michigan; and the 3Rollins School with renal or liver dysfunction, heart fail- of Public Health, Emory University, Atlanta, Georgia. ure, and intravenous iodine contrast and Corresponding author: Guillermo E. Umpierrez, [email protected]. Received 1 February 2013 and accepted 11 May 2013. after surgical procedures (7,8,10). In ad- DOI: 10.2337/dc13-0277. Clinical trial reg. no. NCT01378117, clinicaltrials.gov. dition, the use of thiazolidinediones is This article contains Supplementary Data online at http://care.diabetesjournals.org/lookup/suppl/doi:10 limited by their lag time to active glucose .2337/dc13-0277/-/DC1. control and their tendency to increase in- A slide set summarizing this article is available online. © 2013 by the American Diabetes Association. Readers may use this article as long as the work is properly travascular volume and precipitate or cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/ worsen congestive heart failure and pe- licenses/by-nc-nd/3.0/ for details. ripheral edema (18). 3430 DIABETES CARE, VOLUME 36, NOVEMBER 2013 care.diabetesjournals.org Umpierrez and Associates Since the U.S. approval of incretin and basal bolus insulin with glargine once Outcome measures mimetic agents in 2005–2006, dipeptidyl daily and lispro before meals (Humalog; The primary outcome of the study was to peptidase-4 (DPP-4) inhibitors have been Eli Lilly and Company). Patients treated determine differences in glycemic control rapidly incorporated into the outpatient with sitagliptin received a single dose of as measured by mean daily BG concen- management of T2D (19). These agents 100 mg/day (at any time of day) if GFR tration among treatment groups. Second- improve metabolic control by enhancing .50 mL/min or 50 mg/day if GFR was ary outcomes included differences between endogenous prandial insulin secretion between 30 and 50 mL/min. Patients in treatment groups in any of the following and inhibiting glucagon secretion, thereby the sitagliptin and basal group received a measures: number of BG values within reducing postprandial glucose excursions starting total daily dose (TDD) of glargine range, number of hypoglycemic events (20). The low risk of hypoglycemia and of 0.25 units/kg/day, except for those pa- (BG ,70 and ,40 mg/dL), number of ep- good tolerability of the DPP-4 inhibitors tients $70 years of age and/or with a serum isodes of hyperglycemia (BG .200 mg/dL) (21–23) make them attractive considera- creatinine $2.0 mg/dL who received a after the first day of treatment, TTD of in- tions for use in hospitalized patients. At starting TDD of 0.15 units/kg. Patients in sulin, length of hospital stay, hospital this time, however, no previous studies the basal bolus group were started at a complications, and differences in glycemic have investigated the use of these agents TDD of 0.5 units/kg divided half as insulin control between medicine and surgery in the hospital setting. Accordingly, we glargine once daily and half as insulin lis- patients. conducted a prospective, randomized clin- pro before meals. In patients $70 years of ical trial to determine the safety and efficacy age and/or with a serum creatinine $2.0 Statistical analysis of sitagliptin alone or in combination with mg/dL, the starting TDD in the basal bolus This was a noninferiority study design basal insulin in the management of general group was