Diabetes Control: Insulin, Metformin & Exenatide

Exenatide twice daily plus basal insulin is a good treatment option for patients with type 2 diabetes mellitus (T2DM), including those from Latin American, according to a new study.

Both the glucagon-like peptide-1 receptor agonist (GLP-1RA) exenatide twice daily and prandial insulin lispro, each added to basal insulin glargine, are effective at reducing glycated hemoglobin (HbA1c) in Latin American patients, stated the researchers led by Silvia Beatriz Gorban de Lapertossa of National University of the Northeast School of Medicine in Corrientes, Argentina.

Individualized therapy is important throughout the course of T2DM, but for patients unable to achieve glycemic control with either oral treatment or basal insulin, relatively few options are available.

A multinational, multicenter study of patients who were unable to achieve glycemic control after 12 weeks of basal insulin optimization and metformin, the Basal Insulin Glargine + Exenatide BID vs. Basal Insulin Glargine + Bolus Insulin Lispro study, found that the addition of exenatide twice daily produced a comparable reduction in HbA1c to that of prandial insulin lispro. Treatment with insulin lispro was associated with weight gain and a higher rate of hypoglycemia.

Differences in the effects of these treatments are likely due to their differing mechanisms of action. “GLP-1RAs increase glucose-dependent insulin release and decrease glucose-dependent glucagon release, delay gastric emptying, and reduce food intake. The glucose-dependent nature of GLP-1RAs improves glycemic control at elevated blood glucose levels, without increasing the risk of hypoglycemia. Insulin stimulates glucose reuptake in skeletal muscle and glycogenesis in the liver and inhibits glucagon secretion. When administered exogenously, insulin reaches high concentrations in peripheral tissue, which increases the risk for hypoglycemia and weight gain,” the researchers stated.

They conducted a subgroup analysis from the primary study of 114 patients from Argentina and Mexico. Patients had HbA1c level of 7–10% after 12 weeks of intensive basal insulin optimization before randomization to exenatide twice daily or three-times daily insulin lispro added to insulin glargine and metformin.

The results show after 30 weeks the addition of exenatide or insulin lispro led to significant reductions in HbA1c. Weight was stable in the exenatide group and increased significantly with insulin lispro. Major and minor hypoglycemia occurred less frequently with exenatide (40 events) compared with insulin lispro (253 events).

Gastrointestinal adverse events of nausea, diarrhea, and vomiting occurred more frequently with exenatide than with insulin lispro.

In conclusion, the researchers stated: “This subgroup analysis of Latin American patients unable to achieve glycemic control with titrated basal insulin glargine and metformin alone found that the addition of exenatide twice daily resulted in a comparable reduction in HbA1c to that of insulin lispro, but without any associated weight gain.”

They noted a lower incidence of hypoglycemia and higher rates of gastrointestinal adverse events in patients receiving exenatide twice daily.

“Given the consistency of these results with the primary study, our findings support the efficacy and safety of exenatide twice daily added to basal insulin and metformin in Latin American patients with inadequate glycemic control,” they stated.

Reference: de Lapertosa SB, et al. The effects of exenatide twice daily compared to insulin lispro added to basal insulin in Latin American patients with type 2 diabetes: a retrospective analysis of the 4B trial. Diabetes Res Clin Pract. 2016 Oct 8;122:38-45.