1. The combination of insulin degludec and the GLP1 antagonist, liraglutide, lowered the HbA1c in patients with type II diabetes to a greater extent than up-titration of insulin glargine.
2. Degludec/liraglutide was also associated with less adverse effects, including frequency of hypoglycemic episodes, weight gain, self-reported physical functioning, and overall treatment satisfaction.
Evidence Rating Level: 1 (Excellent)
Study Rundown: For patients with type II diabetes with high HbA1c levels, titration of basal insulin can be challenging due to the increased risk of hypoglycemia and weight gain. As an alternative to increasing insulin doses, adding the GLP1-antagonist, liraglutide, to the basal insulin dose has been suggested. To test the efficacy and safety of this strategy, this phase III trial enrolled patients with persistently elevated HbA1c levels despite being on a stable basal dose of insulin glargine, and randomly assigned them to receive an increased dose of insulin glargine or degludec/liraglutide over 26 weeks. Patients who recieved degludec/liraglutide showed a greater reduction in HbA1c levels compared to those who received increased glargine, including a greater proportion of patients reaching HbA1c levels below 7%. In addition, the degludec/liraglutide group experienced less day-time and nocturnal hypoglycemic episodes and weight gain, and reported improved physical functioning and overall treatment satisfaction. Of note, the degludec/liraglutide cohort did experience greater gastrointestinal symptoms but did not report increased levels of other side effects.
The findings of this study are encouraging, and suggest that once a day degludec/liraglutide administration may be superior to increasing basal insulin glargine in patients with poorly controlled type II diabetes. Additionally, this treatment strategy led to fewer hypoglycemic episodes and less weight gain, likely making it more tolerable to clinicians and patients alike. Further research in other patient populations and with common co-morbidities will be needed to generalize this research further.
Click to read the study, published today in JAMA
Relevant Reading: Management of Hyperglycemia in Type II Diabetes, 2015: A Patient Centered Approach: Update to a Position Statement of the American Diabetes Association and the European Association for the Study of Diabetes
In-Depth [randomized controlled trial]: This phase III clinical trial enrolled 557 patients from 10 countries on stable basal insulin dosing with HbA1c levels between 7.0-10.0%. These patients were randomly assigned to the increased glargine or degludec/liraglutide groups, of which 91% and 86% of patients completed the trial and follow-up, respectively. After 26 weeks of treatment, the degludec/liraglutide cohort was found to have lower HbA1c levels than glargine cohort (degludec/liraglutide HbA1c change -1.81, CI95 -1.94 to -1.68; glargine -1.13, CI95 -1.25 to -1.02). In addition, the addition of degludec/liraglutide decreased the average patient weight (-1.4 kg, CI95 -1.8 to -1.0 kg) compared to glargine, which led to weight gain (1.8 kg, CI95 1.4 to 2.2 kg). The rates of confirmed hypoglycemia events per patient-year of exposure were also reduced in the degludec/liraglutide group compared to glargine group (estimated rate ratio 0.43, CI95 0.30 to 0.61). In addition, there were more patients that had an HbA1c level below 7.0% in the degludec/liraglutide group (increase of 24.6%, CI95 16.7 to 32.5%). Of these patients, there were also reduced rates of weight gain and hypoglycemic episodes (both p < 0.001). On the Treatment Related Impact Measures for Diabetes (TRIM-D) and 36-item Short Form survey (SF-36), patients in the degludec/liraglutide group reported better physical functioning, general health, and treatment satisfaction than the glargine group (p < 0.05). The degludec/liraglutide group had increased complaints of nausea compared to the glargine group (9.4% vs 1.1%).
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