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GLP-1 and basal insulin offer improved glycemic control, weight loss in type 2 diabetes

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A 20-year journey

It has been a 20-year journey, but the combination of GLP-1 agonist and basal insulin has finally arrived as a more powerful and safer alternative to insulin in the management of type 2 diabetes. Perhaps the most practical and immediate issue is whether the fixed-dose combinations of a GLP-1 agonist and basal insulin in development will supersede other approaches. This is an unsettled question, but it seems likely that fixed-dose combinations will be welcomed in view of their convenience and efficacy. The major barrier to widespread adoption of these treatments is cost both GLP-1 agonists and insulin analogues are among the most expensive in diabetes care. One can hope that some incremental cost savings will come with combined products.

Dr. John Buse and Dr. Laura Young of University of North Carolina, Chapel Hill, N.C., made these remarks in an accompanying editorial. Both authors report funding from pharmaceutical manufacturers, including Boehringer Ingelheim, Eli Lilly, Johnson & Johnson, Sanofi. Dr. Buse is a consultant to PhaseBio Pharmaceuticals, and receives stock options and payments.


 

References

Combination treatment with GLP-1 agonist and basal insulin helps diabetes patients achieve glycemic control without increasing their risk of hypoglycemia or weight gain, a new meta-analysis has found.

The research, published online Sept. 12 in The Lancet, suggests that glucagon-like peptide-1 (GLP-1) agonists, injectable agents currently used mainly as second- or third-line treatments after oral diabetes therapies have failed, might merit a more prominent role in the treatment pathway in combination with basal insulin.

The authors of the meta-analysis, led by Conrad Eng of Mount Sinai Hospital, Toronto, analyzed results from 15 studies enrolling 4,348 patients with type 2 diabetes. All the studies compared GLP-1 agonists, including exenatide (Byetta), liraglutide (Victoza), and albiglutide (Tanzeum), and basal insulin with other regimens, which included oral agents with or without insulin, and insulin-only regimens.

A GLP-1 agonist plus basal insulin was associated with a reduction of 0.44% in more lowering of hemoglobin A1c and a near doubling in the likelihood of achieving a target HbA1c of 7% or below (relative risk, 1.92), compared with other diabetes treatments. No increased risk of hypoglycemia was seen associated with the GLP-1 and basal insulin regimens, and a mean reduction in weight of 3.22 kg was seen for these compared to the other treatments. Compared with full basal-bolus insulin regimens, a GLP-1 agonist plus basal insulin was seen associated with minimal reduction in HbA1c (–0.1%), but with lower risk of hypoglycemia (RR 0.67) and a reduction in mean weight of 5.66 kg.

The meta-analysis yielded “robust and consistent findings that lend support to the benefits of GLP-1 agonist and basal insulin combination treatment. Indeed, this consistency is apparent despite the fact that these studies differ in several ways, including the antidiabetic treatments assessed, the background oral antidiabetic drugs, the GLP-1 preparation under study, and the sequence of its initiation in relation to that of basal insulin,” Mr. Eng and his colleagues wrote. They acknowledged as limitations of their study the open-label design, industry funding, and short duration of some of the included clinical trials.

The study had no outside funding; one coauthor, Dr. Bernard Zinman, reported financial relationships with Novo Nordisk, Boehringer Ingelheim, Merck, Eli Lilly, AstraZeneca, Jansen, Takeda, and Sanofi-Aventis. Dr. Ravi Retnakaran, corresponding author, disclosed past compensation from Novo Nordisk and Merck.

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