Efficacy and Safety of Ertugliflozin in Patients With Diabetes Mellitus Inadequately Controlled by Sulfonylurea Monotherapy: a Substudy of VERTIS CV

Abstract

Introduction Sulfonylureas (SU) are commonly used antihyperglycemic agents. VERTIS CV was the cardiovascular outcome study for the sodium-glucose cotransporter 2 inhibitor ertugliflozin. Enrollment of patients in VERTIS CV occurred in two sequential cohorts (Cohort 1 and Cohort 2). Methods This substudy assessed the efficacy and safety of adding ertugliflozin to SU monotherapy. The primary endpoint was the change in HbA1c from baseline at 18 weeks. Results Among the 8246 patients who were randomized in VERTIS CV, 157 patients in Cohort 1 and 135 patients in Cohort 2 were on SU monotherapy at baseline. In the prespecified analysis (Cohort 1 only), the least squares (LS) mean HbA1c change from baseline for placebo, ertugliflozin 5 mg, and ertugliflozin 15 mg was − 0.56%, − 0.91%, and − 0.78%, respectively (placebo-adjusted LS mean [95% CI] change: − 0.35% [− 0.72%, 0.02%]; − 0.22% [− 0.60%, 0.16%] for ertugliflozin 5 and 15 mg, respectively; p > 0.05 for both). In a post-hoc analysis that included Cohorts 1 and 2 ( N = 292), the LS mean HbA1c change from baseline at week 18 for placebo, ertugliflozin 5 mg, and ertugliflozin 15 mg was − 0.31%, − 0.77%, and − 0.68%, respectively (placebo-adjusted change: − 0.46% [− 0.73%, − 0.18%]; − 0.37% [− 0.66%, − 0.09%]; p = 0.001 and 0.01 for ertugliflozin 5 and 15 mg, respectively). In Cohort 1, adverse events were reported in 45.8%, 47.3%, and 25.9% of patients with placebo, ertugliflozin 5 mg, and ertugliflozin 15 mg. The incidence rates of symptomatic hypoglycemia were 0.0%, 5.5%, and 3.7%, respectively, with no cases of severe hypoglycemia. The safety profile was similar for Cohorts 1 and 2 combined. Conclusion The addition of ertugliflozin to SU monotherapy reduced HbA1c but did not result in significant placebo-adjusted reductions from baseline according to the prespecified primary analysis ( n = 157); however, in a post-hoc analysis with a larger patient population ( n = 292), significant and clinically relevant HbA1c reductions were observed. Ertugliflozin was generally well tolerated. Trial Registration ClinicalTrials.gov identifier: NCT01986881. Supplementary Information The online version contains supplementary material available at 10.1007/s13300-021-01018-w.

A network meta-analysis of the effectiveness and safety of different doses of ertugliflozin in the treatment of type 2 diabetes

“…412 first-checked articles [the daTablease and the number of checked-out articles are as follows: PubMed(n=25), Cochrane(n=117), Embase(n=175), CNKI(n=6), Wanfang( n=1), VIP (n=6), CBM (n=6), Web of science (n=76)], remove the weight, read the title and abstract, read the full text further, and finally included 11 RCT studies [9][10][11][12][13][14][15][16][17][18][19] , the literature screening process is shown in Figure 1. The included literatures are all double-blind and multi-center randomized controlled trials, with a total of 5713 patients, and all publications are in English.…”

“…11 studies [9][10][11][12][13][14][15][16][17][18][19] reported the changes in HbA1c levels after the treatment of type 2 diabetes with ertugliflozin. The improvement effect of each treatment group of Ertugliflozin (5,10,15,25 mg) on the HbA1c of T2DM patients was better than that of placebo group, only 15 groups had statistical significance(p<0.05) and the difference was significant.…”

Impute the Missing Data Using Retrieved Dropouts

“…Generally speaking, every clinical study defines intercurrent events somewhat differently. For instance, recent glycemic clinical studies primarily define treatment discontinuation or initiation of rescue therapy as intercurrent events [27][28][29][30]40 . Some lipid-lowering clinical programs might only define treatment discontinuation as intercurrent events 41 , like the data analysis application.…”

Adding Sodium–Glucose Co-Transporter 2 Inhibitors to Sulfonylureas and Risk of Hypoglycemia: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

“…One study included only subjects aged 55 years or more. In eight of the 12 studies (17,21,22,(25)(26)(27)(28)(29)(30)(31)(32)(33) the planned follow-up was 24 weeks or less; one study followed patients for a median time of 48 weeks; three studies followed patients for a median time of over 48 weeks. It was impossible to get specific NNHs for the follow-up period range.…”