Patients with type 2 diabetes mellitus (T2DM) receiving U-500 insulin may benefit from the addition of a glucagon-like peptide-1 (GLP-1) receptor agonist and/or sodium-glucose cotransporter-2 (SGLT-2) inhibitor, according to findings from a study published in the Annals of Pharmacotherapy

Given the limited evidence surrounding the efficacy of these therapies with U-500 insulin, study authors conducted  a retrospective chart review on patients from an endocrinology clinic who initiated a GLP-1 agonist and/or SGLT-2 inhibitor after receiving U-500 insulin for at least 3 months. The primary endpoint of the study was the change in glycosylated hemoglobin (A1c) 3-6 months following the initiation of the GLP-1 agonist or SGLT-2 inhibitor. Secondary endpoints of the study included changes in A1c at 12 months, U-500 insulin total daily dose (TTD), and BMI/body weight, as well as hypoglycemia occurrence. 

The review included 17 patients total (A1c: 8.6 ± 1.1%; TDD: 238.8 ± 88 units; mean BMI: 40.2 ± 7.7kg/m2; body weight: 120.5 ± 20.4kg). Of these patients, 8 (47.1%) initiated a GLP-1 agonist, 6 (35.3%) initiated a SGLT-2 inhibitor, and 3 initiated both. 

The study authors reported that significant reductions in A1c (7.8 ± 1.0%; 0.84% reduction; P =.004) as well as the TDD of U-500 insulin (205.3 ± 77 units; 33.5 unit reduction; P =.031) were observed 3 to 6 months following the addition of a GLP-1 agonist and/or SGLT-2 inhibitor to U-500 insulin. Moreover, the addition of these agents also resulted in significant reductions in mean BMI (38.0± 7.2kg/m2; P =.012) as well as body weight (113.8 ± 17.5kg; P =.015) 12 months postbaseline. 

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The study authors reported that the majority of patients (64.7%) experienced hypoglycemia following the addition of a GLP-1 agonist or SGLT-2 inhibitor to U-500 insulin therapy. Additionally, a 29% increase in the incidence of hypoglycemia was reported following initiation of a GLP-1 agonist or SGLT-2 inhibitor (4 patients prior to addition of therapy vs 9 patients receiving combination therapy; P < .003). 

“Clinically, the addition of a GLP-1 agonist and/or SGLT-2 inhibitor can improve A1c and decrease TDD, BMI, and body weight,” the authors concluded. They added that “the observed increase in hypoglycemia with additional agents further emphasizes that close follow-up and dose reduction of U-500 insulin are critical as additional agents are added to patients’ diabetes regimens.”

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