Hospital Pharmacy - May 2017 - 376

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weight loss from baseline to week 26; estimated
treatment difference was −2.22 kg (95% CI, −2.64 to
−1.8; P < .0001) between insulin degludec/liraglutide and insulin degludec and +2.44 kg (95% CI,
2.02-2.86; P < .001) between insulin degludec/liraglutide and liraglutide.
** Documented symptomatic hypoglycemia occurred in
32% of patients in the insulin degludec/liraglutide
group, 39% in the insulin degludec group, and 7% in
the liraglutide group.
Comments: This study was conducted in 19 countries (the
United States, Australia, Canada, Finland, Germany,
Hungary, India, Ireland, Italy, Malaysia, Mexico, Puerto
Rico, the Russian Federation, Singapore, Slovakia, South
Africa, Spain, Taiwan, Thailand, and the United Kingdom).
Of the 1663 patients randomized, 1444 (87%) completed
the study. The liraglutide group had the highest withdrawal
rate (18%), while 12% of patients withdrew from both the
insulin degludec/liraglutide and insulin degludec groups.
Gastrointestinal (GI) adverse events were the main cause
for study withdrawal in the liraglutide group. A 26-week
extension study (total of 52 weeks of treatment) confirmed
the initial 26-week results and showed the sustainability of
those changes, with no new adverse events or tolerability
issues.8 DUAL II, a trial similar to DUAL I, was a doubleblind study comparing insulin degludec/liraglutide plus
metformin and insulin degludec plus metformin in 413
patients over 26 weeks. As in DUAL I, the insulin degludec/
liraglutide group had better glycemic control than the insulin degludec group.9 A post hoc analysis used data from
DUAL I and DUAL II to determine whether glycemic
response to insulin degludec/liraglutide was faster than the
response to insulin degludec or liraglutide alone; results
show that plasma glucose was reduced to a greater extent
with insulin degludec/liraglutide during the first 12 weeks
than with each component alone.10 Another post hoc analysis used data from the DUAL I extension and DUAL II trials to determine whether the combination was consistently
effective in patients with type 2 diabetes, regardless of the
stage of type 2 diabetes progression; this analysis determined that reduction in HbA1c with insulin degludec/liraglutide was independent of disease duration and previous
insulin dose but varied depending on pretrial oral antidiabetic drug treatment.11
Limitations: This was an open-label study with a short
treatment duration (26 weeks). However, the 26-week
extension study helped to overcome the short duration of
treatment in the DUAL I study.
Drug: Insulin Degludec/Liraglutide versus Unchanged
GLP-1 Receptor Agonist
Reference: Linjawi S, et al, 2016 (DUAL III trial)12
Study Design: Phase 3, randomized, open-label, multicenter study

Hospital Pharmacy 52(5)
Study Funding: Novo Nordisk
Patients: 438 insulin-naive adults with type 2 diabetes
inadequately controlled with a GLP-1 receptor agonist
(liraglutide once daily or exenatide twice daily) and oral
antidiabetic drugs (metformin alone or in combination
with pioglitazone and/or sulfonylurea). Patients were
required to have received treatment with the maximum
approved or tolerated dose of a GLP-1 or oral antidiabetic
drug for at least 90 days before screening. Patients had
HbA1c of 7% to 9% and a BMI of 40 kg/m2 or less. Patients
were excluded if they had received oral antidiabetic drugs
other than metformin, pioglitazone, and a sulfonylurea,
within 90 days of screening. Average baseline characteristics were similar between the 2 study groups (insulin
degludec/liraglutide and unchanged GLP-1 receptor agonist): Patient age was approximately 58 years, BMI was
approximately 33 kg/m2, and HbA1c was approximately
7.8%. In the unchanged GLP-1 receptor agonist group,
79.5% of patients were treated with liraglutide once daily
and 20.5% received exenatide twice daily. Baseline use of
oral antidiabetic drugs was similar in both groups:
Approximately 74% received metformin alone, approximately 21% received metformin plus a sulfonylurea,
approximately 2.5% received metformin plus pioglitazone, and approximately 2% received metformin plus a
sulfonylurea and pioglitazone. Mean duration of treatment with a GLP-1 receptor agonist prior to enrollment
was 468.1 days in the insulin degludec/liraglutide group
and 498.6 days in the unchanged GLP-1 receptor agonist
group. The study was completed by 94.5% of patients in
the insulin degludec/liraglutide group and 80.1% of the
unchanged GLP-1 receptor agonist group.
Intervention: Patients were randomized 2:1 to receive
insulin degludec/liraglutide (n = 292) or unchanged
GLP-1 receptor agonist therapy (n = 146). Insulin
degludec/liraglutide was dosed once daily, preferably at
the same time each day; the dose of insulin degludec/
liraglutide was adjusted twice weekly to achieve a fasting plasma glucose of 72 to 90 mg/dL. No changes in
dosage regimen were made in the GLP-1 receptor agonist group. Any oral antidiabetic drugs patients were
receiving prior to the study were continued unchanged
in both groups.

Results
Primary Endpoint(s)
** HbA1c decreased from 7.8% at baseline to 6.4% at
week 26 in the insulin degludec/liraglutide group and
from 7.7% to 7.4% in the unchanged GLP-1 receptor
agonist group. Mean change from baseline to week 26
was 1.3% and 0.3%, respectively. The estimated treatment difference between the 2 groups was −0.94%
(95% CI, −1.11% to −0.78%).



Table of Contents for the Digital Edition of Hospital Pharmacy - May 2017

Editorial, For Sale: FDA Priority Review Vouchers
Current FDA-Related Drug Information; Approvals, Submission, and Important Labeling Changes for US Marketed Pharmaceuticals
Summaries of Safety Labeling Changes Approved by the FDA: Boxed Warnings
ISMP Adverse Drug Reactions: Levofloxacin-Induced Neuroexcitation and Hallucinations Statin-Induced Muscle Rupture Mefloquine-Induced Rhabdomyolysis Methimazole-Induced
Critical Care Pharmacist Market Perceptions: Comparison of Critical Care Program Directors and Directors of Pharmacy
Capecitabine, Oxaliplatin, and Bevacizumab (BCapOx) Regimen for Metastatic Colorectal Cancer
Clinical Pharmacy Discharge Counseling Service and the Impact on Readmission Rates in High-Risk Patients
Mannitol Prescribing Practices With Cisplatin Before and After an Educational Newsletter Intervention
Pharmacists’ Knowledge of the Cost of Laboratory Testing
Adverse Drug Reaction Reporting Practices Among United Arab Emirates Pharmacists and Prescribers
Postoperative Pain Management With Liposomal Bupivacaine in Patients Undergoing Orthopedic Knee and Hip Arthroplasty at a Community Hospital
Formulary Drug Reviews
Hospital Pharmacy - May 2017 - 317
Hospital Pharmacy - May 2017 - 318
Hospital Pharmacy - May 2017 - 319
Hospital Pharmacy - May 2017 - 320
Hospital Pharmacy - May 2017 - 321
Hospital Pharmacy - May 2017 - 322
Hospital Pharmacy - May 2017 - 323
Hospital Pharmacy - May 2017 - Editorial, For Sale: FDA Priority Review Vouchers
Hospital Pharmacy - May 2017 - 325
Hospital Pharmacy - May 2017 - Current FDA-Related Drug Information; Approvals, Submission, and Important Labeling Changes for US Marketed Pharmaceuticals
Hospital Pharmacy - May 2017 - Summaries of Safety Labeling Changes Approved by the FDA: Boxed Warnings
Hospital Pharmacy - May 2017 - 328
Hospital Pharmacy - May 2017 - 329
Hospital Pharmacy - May 2017 - ISMP Adverse Drug Reactions: Levofloxacin-Induced Neuroexcitation and Hallucinations Statin-Induced Muscle Rupture Mefloquine-Induced Rhabdomyolysis Methimazole-Induced
Hospital Pharmacy - May 2017 - 331
Hospital Pharmacy - May 2017 - 332
Hospital Pharmacy - May 2017 - 333
Hospital Pharmacy - May 2017 - Critical Care Pharmacist Market Perceptions: Comparison of Critical Care Program Directors and Directors of Pharmacy
Hospital Pharmacy - May 2017 - 335
Hospital Pharmacy - May 2017 - 336
Hospital Pharmacy - May 2017 - 337
Hospital Pharmacy - May 2017 - 338
Hospital Pharmacy - May 2017 - 339
Hospital Pharmacy - May 2017 - 340
Hospital Pharmacy - May 2017 - Capecitabine, Oxaliplatin, and Bevacizumab (BCapOx) Regimen for Metastatic Colorectal Cancer
Hospital Pharmacy - May 2017 - 342
Hospital Pharmacy - May 2017 - 343
Hospital Pharmacy - May 2017 - 344
Hospital Pharmacy - May 2017 - 345
Hospital Pharmacy - May 2017 - 346
Hospital Pharmacy - May 2017 - 347
Hospital Pharmacy - May 2017 - Clinical Pharmacy Discharge Counseling Service and the Impact on Readmission Rates in High-Risk Patients
Hospital Pharmacy - May 2017 - 349
Hospital Pharmacy - May 2017 - 350
Hospital Pharmacy - May 2017 - 351
Hospital Pharmacy - May 2017 - 352
Hospital Pharmacy - May 2017 - Mannitol Prescribing Practices With Cisplatin Before and After an Educational Newsletter Intervention
Hospital Pharmacy - May 2017 - 354
Hospital Pharmacy - May 2017 - 355
Hospital Pharmacy - May 2017 - 356
Hospital Pharmacy - May 2017 - Pharmacists’ Knowledge of the Cost of Laboratory Testing
Hospital Pharmacy - May 2017 - 358
Hospital Pharmacy - May 2017 - 359
Hospital Pharmacy - May 2017 - 360
Hospital Pharmacy - May 2017 - Adverse Drug Reaction Reporting Practices Among United Arab Emirates Pharmacists and Prescribers
Hospital Pharmacy - May 2017 - 362
Hospital Pharmacy - May 2017 - 363
Hospital Pharmacy - May 2017 - 364
Hospital Pharmacy - May 2017 - 365
Hospital Pharmacy - May 2017 - 366
Hospital Pharmacy - May 2017 - Postoperative Pain Management With Liposomal Bupivacaine in Patients Undergoing Orthopedic Knee and Hip Arthroplasty at a Community Hospital
Hospital Pharmacy - May 2017 - 368
Hospital Pharmacy - May 2017 - 369
Hospital Pharmacy - May 2017 - 370
Hospital Pharmacy - May 2017 - 371
Hospital Pharmacy - May 2017 - 372
Hospital Pharmacy - May 2017 - 373
Hospital Pharmacy - May 2017 - Formulary Drug Reviews
Hospital Pharmacy - May 2017 - 375
Hospital Pharmacy - May 2017 - 376
Hospital Pharmacy - May 2017 - 377
Hospital Pharmacy - May 2017 - 378
Hospital Pharmacy - May 2017 - 379
Hospital Pharmacy - May 2017 - 380
Hospital Pharmacy - May 2017 - 381
Hospital Pharmacy - May 2017 - 382
Hospital Pharmacy - May 2017 - 383
Hospital Pharmacy - May 2017 - 384
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