Some veterans with type 2 diabetes patients can’t reach their hemoglobin A1c goal despite using metformin, basal insulin and a sulfonylurea. What should come next?

A study in Diabetes Spectrum provided a possible answer to that question. It pointed out, however, that, despite advances in the management of patients with type 2 diabetes, data on the optimal way to intensify treatment is lacking.1

Researchers conducted a single-center, retrospective cohort study of U.S. veterans receiving metformin, basal insulin, and a sulfonylurea who were started either on a third noninsulin agent or prandial insulin. The study team was from the Departments of Pharmacy at the Lebanon, PA, VAMC and Mount Sinai Hospital in New York.

Defined as the primary outcome for the study was change in A1c at 6 months after treatment intensification, while change in weight at 6 months, change in A1c at 1 year, percentage of patients achieving an A1C below 7.5% at 1 year, documented episodes of hypoglycemia and time to progression to prandial insulin were all considered secondary outcomes.

Of the 62 patients included in the study, 28 received prandial insulin and 34 were treated with a noninsulin agent.
Results documented no significant difference in A1c change between the two treatment arms at either 6 months (-0.53 vs. -0.84%, P = 0.31) or 1 year (-0.67 vs. -0.86%, P = 0.61) after intervention.

At the same time, patients receiving noninsulin agents gained significantly less weight at 6 months (-2.09 vs. 1.99 kg, P <0.01), while also experiencing fewer annual episodes of hypoglycemia (1.0 vs. 2.6, P = 0.01).

“These results highlight that, in select patients, noninsulin therapies can be added to a backbone of metformin, basal insulin, and a sulfonylurea with similar A1C reductions but improved metabolic parameters relative to intensive insulin therapy,” study authors concluded.

Researchers also reported that patients receiving a specific noninsulin agents, a glucagon-like peptide 1 receptor agonist, were found to be more likely to have an A1C of less than 7.5% at 1 year, as compared to patients receiving a dipeptidyl peptidase 4 inhibitor — 50 vs. 13%, P = 0.05.

Those findings were in line with a study published earlier this year in the journal Diabetes, Obesity & Metabolism. Canadian researchers found that “GLP‐1 agonists yield greater reduction in HbA1c and weight as compared to DPP‐4 inhibitors, with increased incidence of gastrointestinal symptoms but not hypoglycemia. Replacing a DPP‐4 inhibitor with GLP‐1 agonist provides additional benefits in glycemic control and weight loss.”

1. Santeusanio AD, Bowen MM. Short-Term Outcomes for Veterans Receiving Basal Insulin, Metformin, and a Sulfonylurea Who Are Started on a Third Noninsulin Agent Versus Prandial Insulin. Diabetes Spectr. 2018 Aug;31(3):261-266. doi: 10.2337/ds17-0068. PubMed PMID: 30140142; PubMed Central PMCID: PMC6092894.

2. Tran S, Retnakaran R, Zinman B, Kramer CK. Efficacy of glucagon-like peptide-1 receptor agonists compared to dipeptidyl peptidase-4 inhibitors for the management of type 2 diabetes: A meta-analysis of randomized clinical trials. Diabetes Obes Metab. 2018 Feb;20 Suppl 1:68-76. doi: 10.1111/dom.13137. Review.PubMed PMID: 29364587.