Review: In type 2 diabetes, GLP-1 agonists plus basal insulin reduce HbA1c without increasing hypoglycemia

Combination treatment with a glucagon-like peptide-1 receptor (GLP-1) agonist and basal insulin was associated with lower HbA1c values, less weight gain, and similar hypoglycemia rates compared to other type 2 diabetes treatment regimens, according to a meta-analysis. The analysis of 15 trials found a 0.44% decrease in mean HbA1c, an almost doubled likelihood of achieving an HbA1c ≤7.0%, and a mean reduction in weight of 3.22 kg in the GLP-1 patients versus control treatment groups.

The study was published online Sept. 11, 2014, by The Lancet, and a summary was published in the October 2014 ACP Diabetes Monthly. The following commentary by Naykky Singh Ospina, MD, and Victor M. Montori, MD, MSc, was published in the ACP Journal Club section of the Jan. 20, 2015, Annals of Internal Medicine.

How clinicians and patients should combine antidiabetes agents to improve diabetes control and reduce the risk for complications is unclear. Recent guidelines recommend engaging patients in shared decision-making, which requires trustworthy information about the benefits, harms, and inconveniences of the alternatives. Beyond effects on HbA1c levels, no reliable data distinguish available agents by their effects on patient-important benefits or long-term harms. Of note, GLP-1 agonists are costly, and gastrointestinal side effects reduce their tolerability.

The review by Eng and colleagues found that the known and usually desirable effects of GLP-1 agonists—glycemic control, weight loss, reduced hypoglycemia—are maintained when they are used in combination with basal insulin. Between-study differences in patients (e.g., degree of insulin deficiency) and comparisons (use of other antidiabetes agents) contribute to inconsistent results and call into question the applicability of these findings to patients in practice. The included trials had short durations and could not assess the effect of combination therapy on diabetes complications. Also, 12 of the 15 randomized, controlled trials included in the review were sponsored by industry, which offers an alternative explanation for the favorable findings supporting GLP-1 agonist use. At best, the review by Eng and colleagues provides low- to moderate-quality evidence that the known effects of GLP-1 agonists remain when used in combination with basal insulin.

Patients and clinicians will need to make decisions using this evidence, despite its limitations. In this context, informed preferences of patients, after evaluating risks and benefits of the alternatives, should play a major role in designing evidence-based and patient-centered diabetes regimens.