We're unable to sign you in at this time. Please try again in a few minutes.
We were able to sign you in, but your subscription(s) could not be found. Please try again in a few minutes.
There may be a problem with your account. Please contact the AMA Service Center to resolve this issue.
Contact the AMA Service Center:
Telephone: 1 (800) 262-2350 or 1 (312) 670-7827  *   Email: subscriptions@jamanetwork.com
Error Message ......
Original Investigation |

Effect of Adding Liraglutide vs Placebo to a High-Dose lnsulin Regimen in Patients With Type 2 Diabetes A Randomized Clinical Trial

Anna Vanderheiden, MD1; Lindsay Harrison, MD1,2; Jeremy Warshauer, MD1; Xilong Li, PhD, MBA3; Beverley Adams-Huet, MSc3,4; Ildiko Lingvay, MD, MPH, MSCS1,3
[+] Author Affiliations
1Division of Endocrinology, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas
2Texas Diabetes and Endocrinology, Austin
3Division of Biostatistics, Department of Clinical Sciences, University of Texas Southwestern Medical Center, Dallas
4Division of Mineral Metabolism, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas
JAMA Intern Med. 2016;176(7):939-947. doi:10.1001/jamainternmed.2016.1540.
Text Size: A A A
Published online

Importance  An increasing number of patients with type 2 diabetes are treated with high doses of insulin. Such treatment is associated with weight gain, hypoglycemia, and high treatment burden.

Objective  To assess the effectiveness and safety of adding a glucagon-like peptide 1 receptor agonist to the treatment regimen of patients with type 2 diabetes requiring therapy with high-dose insulin.

Design, Setting, and Participants  This clinical trial was a double-blind, placebo-controlled, randomized (1:1) study with 6 months of follow-up, conducted from August 13, 2012, to February 9, 2015, at ambulatory clinics at the University of Texas Southwestern Medical Center and Parkland Hospital. Participants were 71 patients with uncontrolled type 2 diabetes (glycated hemoglobin level, 7.5%-11.0%) using more than 1.5 U/kg/d of insulin.

Interventions  Subcutaneous injection of liraglutide (1.8 mg/d) or matching placebo for 6 months.

Main Outcomes and Measures  The primary outcome was the change in glycated hemoglobin level. Secondary outcomes were changes in weight, hypoglycemia rate, insulin dosage, and quality-of-life measures.

Results  Among 71 patients, 45 (63%) were female. The mean (SD) age of patients was 54.2 (7.4) years, with a mean (SD) type 2 diabetes duration of 17.9 (8.4) years and a mean (SD) total daily dose of insulin of 247.0 (95.1) U. Ninety-three percent (66 of 71) of participants completed all scheduled visits. The glycated hemoglobin level improved from a mean (SD) of 9.0% (1.2%) to 7.9% (1.1%) in the liraglutide group (P < .001) and remained unchanged (8.9%) in the placebo group, with an estimated treatment difference of 0.9% (95% CI, −1.5 to −0.4) (P = .002). Weight decreased from a mean (SD) of 114.6 (21.4) kg to 113.6 (20.8) kg in the liraglutide group vs a mean (SD) increase from 116.1 (26.6) kg to 117.2 (27.2) kg in the placebo group, with a treatment difference of −2.3 kg (95% CI, −4.3 to −0.4 kg) (P = .02). The total daily dose of insulin decreased 11.5% (95% CI, −21.8% to −1.1%) in the liraglutide group (P = .20). The hypoglycemia rate was higher in the first month after initiation of liraglutide compared with placebo (2.30 vs 0.91 events per person-month, P = .01), while the overall hypoglycemia rate over the entire follow-up was similar between groups (P = .11). Glycemia control perception, satisfaction with insulin treatment, and willingness to continue insulin use improved more in the liraglutide group.

Conclusions and Relevance  Liraglutide added to high-dose insulin therapy improved glycemic control, decreased body weight, and enhanced treatment satisfaction in this difficult-to-treat patient population with high-dose insulin requirements. Further studies are warranted to confirm these findings and evaluate the long-term risk and benefit of this treatment option.

Trial Registration  clinicaltrials.gov Identifier: NCT01505673

Figures in this Article

Sign in

Purchase Options

• Buy this article
• Subscribe to the journal
• Rent this article ?


Place holder to copy figure label and caption
Figure 1.
Consolidated Standards of Reporting Trials Diagram

DPPIV indicates dipeptidyl peptidase IV inhibitor; GFR, glomerular filtration rate; HbA1c, glycated hemoglobin.

Graphic Jump Location
Place holder to copy figure label and caption
Figure 2.
Primary and Main Secondary Study Outcomes

Hypoglycemia is a capillary glucose level of less than 70 mg/dL (to convert glucose level to millimoles per liter, multiply by 0.0555). Quality of life was assessed on a scale of 1-5 using a modified Diabetes Quality of Life Clinical Trial Questionnaire.11 A negative number represents improvement from baseline. HbA1c indicates glycated hemoglobin; IRR, incident rate ratio; L-P, ratio of liraglutide to placebo; R, randomization; TDD, total daily dose.

aP < .01.

Graphic Jump Location




Also Meets CME requirements for:
Browse CME for all U.S. States
Accreditation Information
The American Medical Association is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The AMA designates this journal-based CME activity for a maximum of 1 AMA PRA Category 1 CreditTM per course. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Physicians who complete the CME course and score at least 80% correct on the quiz are eligible for AMA PRA Category 1 CreditTM.
Note: You must get at least of the answers correct to pass this quiz.
Please click the checkbox indicating that you have read the full article in order to submit your answers.
Your answers have been saved for later.
You have not filled in all the answers to complete this quiz
The following questions were not answered:
Sorry, you have unsuccessfully completed this CME quiz with a score of
The following questions were not answered correctly:
Commitment to Change (optional):
Indicate what change(s) you will implement in your practice, if any, based on this CME course.
Your quiz results:
The filled radio buttons indicate your responses. The preferred responses are highlighted
For CME Course: A Proposed Model for Initial Assessment and Management of Acute Heart Failure Syndromes
Indicate what changes(s) you will implement in your practice, if any, based on this CME course.


Some tools below are only available to our subscribers or users with an online account.

0 Citations

Sign in

Purchase Options

• Buy this article
• Subscribe to the journal
• Rent this article ?

Related Content

Customize your page view by dragging & repositioning the boxes below.

Articles Related By Topic
Related Collections
PubMed Articles