The health and economic costs of diabetes are enormous. Considerable efforts are being made to develop new and more effective treatments for the disease.
The sodium-glucose cotransporter type 2 (SGLT2) inhibitors are a newer class of drugs being developed as treatment for diabetes. SGLT2 is a low affinity, high capacity glucose transporter located in the proximal tubule in the kidneys. It plays a role in the recovery of glucose from glomerular filtrate. Inhibition of SGLT2 promotes glucose excretion in urine, and consequent reduction in plasma glucose. The insulin-independent mechanism of action of this class of drugs along with its favorable safety profile has made it a very promising approach to treat type 2 diabetes (T2DM) patients.
Ertugliflozin (ERTU) is an investigational oral SGLT2 inhibitor currently undergoing phase III clinical trials.
Merck & Co., Inc., in collaboration with Pfizer Inc. have announced the results of two phase III clinical trials of ERTU, namely, VERTIS Mono and VERTIS Factorial. The results of these trials were recently presented at the American Diabetes Association’s 76th Scientific Sessions (ADA 2016) held at New Orleans from June 10-14, 2016.
The VERTIS Mono is a 52-week randomized, double-blind, placebo-controlled trial evaluating the efficacy and safety of ERTU compared with placebo in patients with T2DM and inadequate glycemic control on diet and exercise (ClinicalTrials.gov Identifier: NCT01958671). At week 26, patients randomized to ERTU 5 mg and 15 mg showed significant A1C reductions of 0.99% and 1.16% respectively, compared to placebo. The study also met its secondary endpoint, showing that significantly greater number of patients taking ERTU 5 mg and 15 mg achieved their A1C treatment goal of less than 7.0% compared to placebo. Overall adverse event rates were comparable across arms while the rate of serious adverse events was low across groups. A higher incidence of genital mycotic infections was observed in female patients taking either doses of ERTU compared to placebo.
The VERTIS Factorial trial evaluated the co-administration of ERTU and the DPP-4 inhibitor JANUVIA® (sitagliptin [SITA]) in a 26-week study (ClinicalTrials.gov Identifier: NCT02099110). Combination therapy of 5 mg or 15 mg ERTU with 100 mg SITA was found to be significantly more effective in reducing A1C compared to either therapy alone. In addition, significantly greater number of patients in the combination treatment arms achieved an A1C goal of less than 7.0% compared to placebo. Combination therapy was also significantly more effective in reducing fasting plasma glucose, body weight, and blood pressure, compared to ERTU and SITA monotherapies. Adverse events were similar across groups, except for genital mycotic infections, which were observed at a higher rate in the ERTU alone group.
Though current trial data do not indicate any advantage for ERTU monotherapy over other SGLT2 inhibitors, it is believed that a fixed dose combination of ERTU and SITA would provide a more convenient option while intensifying monotherapy with Januvia. Merck and Pfizer plan to submit New Drug Applications to the U.S. FDA for ERTU and the two fixed-dose combination tablets (ERTU plus JANUVIA, and ERTU plus metformin) by the end of 2016.
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World Health Organization. Diabetes Factsheet, June 2016.
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Dagogo-Jack S, Davies M, Frias J, et al. Ertugliflozin effectively improves glycemic control as monotherapy in patients with T2DM. Paper presented at: ADA 76th Scientific Sessions; June 2016; New Orleans, LA. Abstract number: 130-LB.
Eldor R, Pratley R, Golm G, et al. Effect of ertugliflozin plus sitagliptin on glycemic control vs. either treatment alone in subjects with T2DM inadequately controlled with metformin. Paper presented at: ADA 76th Scientific Sessions; June 2016; New Orleans, LA. Abstract number: 125-LB.