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Clinical Trial
. 2019 Apr;21(4):1027-1036.
doi: 10.1111/dom.13631. Epub 2019 Feb 14.

Long-term efficacy and safety of ertugliflozin in patients with type 2 diabetes mellitus inadequately controlled with metformin monotherapy: 104-week VERTIS MET trial

Silvina Gallo  1 , Bernard Charbonnel  2 , Allison Goldman  3 , Harry Shi  4 , Susan Huyck  5 , Amanda Darekar  6 , Brett Lauring  5 , Steven G Terra  7
Affiliations
Clinical Trial

Long-term efficacy and safety of ertugliflozin in patients with type 2 diabetes mellitus inadequately controlled with metformin monotherapy: 104-week VERTIS MET trial

Silvina Gallo et al. Diabetes Obes Metab. 2019 Apr.

Abstract

Aim: To evaluate the long-term efficacy and safety of ertugliflozin in adults with type 2 diabetes mellitus inadequately controlled on metformin.

Materials and methods: A 104-week Phase III, randomized double-blind study with a 26-week placebo-controlled period (Phase A) and a 78-week period (Phase B) where blinded glimepiride was added to non-rescued placebo participants with fasting fingerstick glucose ≥6.1 mmol/L. Results through week 104 are reported.

Results: Mean (standard error) change in HbA1c from baseline was -0.7% (0.07) and -1.0% (0.07) at week 52; -0.6% (0.08) and -0.9% (0.08) at week 104 for ertugliflozin 5 and 15 mg. At week 52, 34.8% and 36.6% participants had HbA1c <7.0%, and 24.6% and 33.7% at week 104, for ertugliflozin 5 and 15 mg. Ertugliflozin reduced fasting plasma glucose (FPG), body weight and systolic blood pressure (SBP) from baseline through week 104. The incidence of female genital mycotic infections (GMIs) was higher with ertugliflozin, and symptomatic hypoglycaemia was lower for ertugliflozin versus placebo/glimepiride. Minimal bone mineral density (BMD) changes were observed, similar to placebo/glimepiride, except at total hip where reduction in BMD was greater with ertugliflozin 15 mg versus placebo/glimepiride: difference in least squares means (95% CI) -0.50% (-0.95, -0.04) at week 52 and -0.84% (-1.44, -0.24) at week 104.

Conclusions: Ertugliflozin maintained improvements from baseline in HbA1c, FPG, body weight and SBP through week 104. Ertugliflozin was well tolerated, with non-clinically relevant changes in BMD. Compared with placebo/glimepiride, ertugliflozin increased female GMIs, but reduced the incidence of symptomatic hypoglycaemia. ClinicalTrials.gov Identifier: NCT02033889.

Keywords: bone mineral density; durability; ertugliflozin; type 2 diabetes mellitus.

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Conflict of interest statement

Author contributions

All authors critically reviewed the draft manuscript and approved the final version of the manuscript for publication. A. D., S. G. T. and B. L. were involved in the conception/design of the study. S. G., A. G., H. S. and A. D. were involved in the acquisition of data for the study. All authors were involved in data analysis and interpretation of the data.

Data accessibility

Upon request, and subject to certain criteria, conditions and exceptions (see https://www.pfizer.com/science/clinical-trials/trial-data-and-results for more information), Pfizer will provide access to individual de‐identified participant data from Pfizer‐sponsored global interventional clinical studies conducted for medicines, vaccines and medical devices (1) for indications that have been approved in the United States and/or European Union, or (2) in programmes that have been terminated (i.e. development for all indications has been discontinued). Pfizer will also consider requests for the protocol, data dictionary, and statistical analysis plan. Data may be requested from Pfizer trials 24 months after study completion. The de‐identified participant data will be made available to researchers whose proposals meet the research criteria and other conditions, and for which an exception does not apply, via a secure portal. To gain access, data requestors must enter into a data access agreement with Pfizer.

Figures

Figure 1
Figure 1
(A) HbA1c change from baseline over time; percentage of participants with HbA1c (B) <7.0% (53 mmol/mol) and (C) <6.5% (48 mmol/mol) at weeks 52 and 104; (D) change in FPG from baseline to weeks 52 and 104. Abbreviations: BL, baseline; FPG, fasting plasma glucose; SE, standard error
Figure 2
Figure 2
Change in (A) body weight, (B) SBP and (C) DBP over time. Abbreviations: BL, baseline; DBP, diastolic blood pressure; SBP, systolic blood pressure; SE, standard error
Figure 3
Figure 3
Mean change from baseline in eGFR over time. Abbreviations: BL, baseline; eGFR, estimated glomerular filtration rate; SE, standard error
Figure 4
Figure 4
LS mean (95% CI)† percentage change from baseline to weeks 52 and 104 in BMD as measured by DXA at (A) the lumbar spine, (B) femoral neck, (C) total hip and (D) distal forearm. Abbreviations: BMD, bone mineral density; CI, confidence interval; LS, least squares. † Based on longitudinal data analysis model with fixed effects for treatment, time, prior antihyperglycaemic medication (metformin monotherapy or metformin and another antihyperglycaemic agent), baseline estimated glomerular filtration rate (continuous), menopausal status (men, premenopausal women, women who are perimenopausal or <3 years postmenopausal, women who are ≥3 years postmenopausal) and the interaction of time by treatment
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