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Long-acting basal insulin can be given with a glucagon-like peptide-1 receptor agonist (GLP-1RA) for treating patients with type 2 diabetes. In this industry-sponsored, open-label trial, 557 diabetic adults who had been taking glargine plus metformin were randomized to once-daily injection of basal insulin (glargine) alone or once-daily injection of a fixed-ratio combination of basal insulin degludec plus the GLP-1RA liraglutide. Fixed-combination degludec/liraglutide is not yet FDA approved; the two components are available separately as Tresiba and Victoza, respectively.
At baseline, mean age was 59 years, mean diabetes duration was 11 years, and mean glycosylated hemoglobin (HbA1c) was 8.3%. Both glargine and combination degludec/liraglutide were adjusted to achieve fasting blood glucose levels of 72 to 90 mg/dL. At 26 weeks, these statistically significant differences were noted:
Mean HbA1c had fallen by 1.8% with degludec/liraglutide and by 1.1% with glargine.
Mean daily insulin dose was 41 units with degludec/liraglutide and 66 with glargine.
Mean weight was 1.4 kg lower with degludec/liraglutide and 1.8 kg higher with glargine.
Hypoglycemia was less common with degludec/liraglutide than with glargine (2.2 vs. 5.0 episodes per patient-year), although only one episode was serious.
Nausea was more common in degludec/liraglutide patients than in glargine patients (9% vs. 1%).
Lingvay I et al. Effect of insulin glargine up-titration vs insulin degludec/liraglutide on glycated hemoglobin levels in patients with uncontrolled type 2 diabetes: The DUAL V Randomized Clinical Trial. JAMA 2016 Mar 1; 315:898. (http://dx.doi.org/10.1001/jama.2016.1252)
Comment
This study suggests that achieving tight glycemic control (e.g., target fasting glucose, <100 mg/dL; target HbA1c, <7%) while minimizing hypoglycemia can be accomplished more readily with basal insulin plus a GLP-1RA than with basal insulin alone. But an important question, not discussed by the authors, is whether this degree of glycemic control is worthwhile for patients like those in this trial — middle-aged or older adults with longstanding type 2 diabetes. Notably, the ACCORD, ADVANCE, and VADT trials did not convincingly demonstrate overall clinical benefit from tight control in this patient population (NEJM JW Gen Med Jul 1 2008 and N Engl J Med 2008; 358:2560 and 2545; NEJM JW Gen Med Jan 15 2009 and N Engl J Med 2009; 360:129).