Liraglutide in people treated for type 2 diabetes with multiple daily insulin injections

Janet Kairu, Mercer University College of Pharmacy

The American Diabetes Association recommends performing an A1C test at least two times a year in patients who are meeting treatment goals (and who have stable glycemic control) and quarterly in patients whose therapy has changed or who are not meeting glycemic goals.1

Diabetes has been listed as a leading cause of death in the U.S. and the World Health Organization (WHO) predicts that diabetes-related deaths will double between 2005 and 2030 worldwide.2, 3

A review of two large landmark studies, the Diabetes Control and Complications Trial (DCCT) and United Kingdom Prospective Diabetes Study (UKPDS) have demonstrated the beneficial effects of maintaining good glycemic control on the development and progression of diabetic complications in type 1 and type 2 diabetes respectively, with the principal goals of treatment being to prevent acute and chronic complications and thus improve quality of life and avoid premature diabetes-associated death. 4, 5

Table 1.

Liraglutide in people treated for type 2 diabetes with multiple daily insulin injections. 6
Design Randomized, double blind, placebo controlled trial; N = 124
Objective To determine the effects of liraglutide on glycemic control in people with type 2 diabetes treated with multiple daily insulin injections
Study Groups Liraglutide (n = 64) and placebo (n = 60)
Methods Liraglutide or placebo was administered at a dose of 0.6 mg during week one, 1.2 mg during week two, and 1.8 mg during week three and onwards.
Duration Twenty four weeks
Primary Outcome Measure Change in HbA1c level from baseline to week 24
Baseline Characteristics Variable Liraglutide group

(n = 64)

Placebo group

(n = 60)

Age (years) 63.7 (8.2); 65.9 (44.1; 78.0) 63.5 (7.7); 65.0 (38.9; 77.3)
Diabetes duration (years) 17.3 (7.6); 16.5 (4; 40) 17.0 (8.1); 16 (2; 35)
Metformin users 44 (68.8) 44 (73.3)
Total daily basal insulin dose (units) 57.4 (25.8); 55.0 (12.0; 130.0) 58.9 (26.4); 58.0 (18.0; 130.0)
Total daily meal insulin dose (units) 47.9 (25.4); 40.0 (12.0; 114.0) 46.8 (26.6); 41.0 (8.0; 165.0)
Total daily meal and basal insulin (units) 105.3 (44.5); 101.0 (28.0; 228.0) 105.7 (41.2); 102.0 (42.0; 230.0)
Total no. of insulin injections 4.5 (0.9);4.0 (3.0; 9.0) 4.4 (0.6); 4.0 (3.0; 6.0)
Weight (kg) 98.9 (14.0); 100.4 (69.0; 134.9) 100.0 (14.8); 96.5 (72.5; 139.2)
Body mass index (kg/m2) 33.7 (4.3); 33.4 (27.3; 44.0) 33.5 (4.0); 33.6 (27.7; 43.0)
Fasting Plasma glucose (mmol/L) 9.9 (3.1); 9.4 (4.2; 17.9) 9.4 (2.5); 9.5 (2.5; 19.6)
HbA1c (IFCC; mmol/mol)

IFCC= International Federation of Clinical Chemistry

74.9 (10.9); 73.5 (53; 103) 74.4 (11.9); 74 (54; 101)
HbA1c (NGSP; %)

NGSP= National Glycohaemoglobin Standardization Program.

9.0 (1.0); 8.9 (7.0; 11.6) 9.0 (1.1); 8.9 (7.1; 11.4)
Results Variable Liraglutide group (n=63)

Mean (SD); median (minimum; maximum)

Placebo group (n=59)

Mean (SD); median (minimum; maximum)

p-value Difference between groups: adjusted mean (95% CI)
 HbA1c (IFCC; mmol/mol) −16.90 (10.34); −18 (−46; 11) −4.54 (9.73); −4 (−26; 23) <0.001 -12.3 (-15.8 to -8.8)
 HbA1c (IFCC; mmol/mol) −1.55 (0.95); −1.65 (−4.21; 1.01) −0.42 (0.89); −0.37 (−2.38; 2.11) <0.001 -1.13 (-1.45 to -0.81)
Adverse Events Common Adverse Events:

Gastrointestinal symptoms; 30 (46.9%) in the liraglutide group and eight (13.3%) in the placebo group.

Nausea were 21 (32.8%) and 1 (1.7%)

Diarrhea were five (7.8%) and three (5.0%)

Serious Adverse Events: three (4.7%) participants in the liraglutide group and four (6.7%) in the placebo group had any serious adverse event
Percentage that Discontinued due to Adverse Events: None
Study Author Conclusions Liraglutide improves glycaemia control in people with type 2 diabetes treated with multiple daily insulin injections and long duration of disease.

Adding liraglutide to multiple daily insulin injections at late stages of type 2 diabetes was associated with improved glycemic control, reduced body weight and lower total daily insulin doses.  Masked continuous glucose monitoring was performed during the trial to obtain estimates of glucose levels every minute, which showed that glycemic variability was reduced in patients treated with liraglutide.

Besides improvement in glycemic control and weight reduction, participants experiencing large fluctuations in glucose levels could benefit from the addition of liraglutide to their treatment regimen.  In the study, the standard deviation of glucose levels was significantly reduced after treatment with liraglutide. Systolic blood pressure was also reduced, by approximately 5 mm Hg, which may also be a cardio protective benefit.

 

References

 

  1. Krader CG. American Diabetes Association. Diabetes clinical practice recommendations focus attention on individualization of care. Med Econ. 2014;91(16):22.
  1. Centers for Disease Control and Prevention (CDC) National Diabetes Fact Sheet: General information and national estimates on diabetes in the United States, 2007. Available at:cdc.gov/diabetes/pubs/pdf/ndfs_2007.pdf. Accessed November 1, 2015.
  2. Wild S, Roglic G, Green A, et al. Global prevalence of diabetes, estimates for the year 2000, and projections for 2030. Diabetes Care. 2004;27:1047–1053.
  1. Nathan DM, Cleary PA, Backlund JY, et al. Intensive diabetes treatment and cardiovascular disease in patients with type 1 diabetes. N Engl J Med. 2005;353(25):2643-53.
  1. King P, Peacock I, Donnelly R. The UK Prospective Diabetes Study (UKPDS): clinical and therapeutic implications for type 2 diabetes.British Journal of Clinical Pharmacology. 1999;48(5):643-648.
  1. Lind M, Hirsch IB, Tuomilehto J, et al. Liraglutide in people treated for type 2 diabetes with multiple daily insulin injections: randomised clinical trial (MDI Liraglutide trial). BMJ. 2015;351:h5364.
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