Study assesses effect of new add-on therapy.
Currently, the treatment options for type 1 diabetes are fairly limited. Usual care consists largely of individually titrated basal bolus insulin regimens. While effective, there are risks associated with insulin titration. Most notably, hypoglycemia and weight gain. Subetta is a drug that is currently undergoing phase 3 clinical trials for the treatment of impaired glucose tolerance. This antidiabetic medication is an oral polyclonal antibody mixture that exerts its effect by stimulating the Beta subunit of insulin receptors as well as endothelial nitric oxide (NO) synthase. By activating insulin receptors, Subetta exerts its antihyperglycemic effect primarily by stimulating uptake of glucose by muscle cells. Subetta may also confer a protective effect against endothelial dysfunction via its stimulation of endothelial NO synthase. This trial aims to determine if using Subetta as an add-on therapy to basal bolus insulin will confer any additional glycemic benefit in people who have type 1 diabetes.
In order to determine causality, a randomized, double blind, placebo-controlled trial was selected as the study design. The primary outcome of the study was change in hemoglobin A1c (HbA1c) from baseline. Fasting blood glucose, insulin doses, body mass index (BMI) / weight, and safety were also monitored during the study. Patients were considered for inclusion if they were poorly controlled on a relatively stable basal bolus insulin regimen (HbA1c between 7.0 and 10.0%). The exclusion criteria were a bit more extensive and included: any micro- or macrovascular diabetes complications, eGFR < 60 mL/min/1.73 m2, uncontrolled hypertension, severe complications of other diseases, history of or present cancer, history of bariatric surgery, history of pancreatectomy, history of kidney transplant, hypertriglyceridemia, and pregnancy or breastfeeding. Once patients were deemed eligible for inclusion, they were randomized, via interactive voice / web response randomization system, into either the intervention (receiving 1 Subetta tablet 4 times daily) or the control group (receiving an identical placebo tablet 4 times daily). Throughout the study, participants continued basal bolus insulin therapy and were instructed to self-adjust their insulin regimen based on home blood glucose readings. Participants were assessed physically at baseline and at 2-week intervals for the duration of the 36-week trial. HbA1c was evaluated at baseline and then again at the end of the trial, 3 months (36 weeks) from the initial measurement.
Of the 200 patients assessed for inclusion, 151 were deemed eligible and randomized into their respective groups, achieving a reported power of 80% for detecting a difference in the primary outcome. Baseline characteristics between groups were equivalent. For the primary outcome, a statistically significant reduction in HbA1c was observed in the intervention group when compared to the control group (-0.59 vs. -0.20 respectively, p = 0.028). Likewise, there was a statistically significant difference in reduction of fasting blood glucose, in favor of the intervention group (-0.8 vs. 1.1 mmol/L for the intervention group and control group respectively, p = 0.029). However, there were no statistically significant differences in insulin doses, BMI / weight, or incidence of reported adverse events.
The results of this study seem to indicate that Subetta may provide additional antihyperglycemic effect in people who have type 1 diabetes that is poorly managed by basal bolus insulin therapy. While the evidence provided by this study supports the statistical significance of this added benefit, the difference is only 0.39% reduction in HbA1c when compared to the control group. Therefore, the clinical significance of this treatment option would need to be determined on a case-by-case basis by weighing the risks and benefits of each treatment.
- Subetta is in phase 3 clinical trials and is being review by the FDA for approval.
- Subetta seems to offer a small but statistically significant additional blood glucose-lowering effect in people with type 1 diabetes that is not managed with basal bolus insulin regimens.
- Subetta, as add-on therapy to basal bolus insulin, does not seem to increase the likelihood of significant adverse events (i.e. hypoglycemia).
Mkrtumyan, Ashot, et al. “Efficacy and Safety of Subetta Add-on Therapy in Type 1 Diabetes Mellitus: The Results of a Multicenter, Double-Blind, Placebo-Controlled, Randomized Clinical Trial.” Diabetes Research and Clinical Practice, vol. 142, 2018, pp. 1–9., doi:10.1016/j.diabres.2018.04.044.
Michael Zaccaro, Pharm. D. Candidate 2019, LECOM School of Pharmacy