Spotlight on ertugliflozin and its potential in the treatment of type 2 diabetes: evidence to date

Cinti, Francesca; Moffa, Simona; Impronta, Flavia; Cefalo, Consuelo; Sun, Vinsin A.; Sorice, Gian Pio; Mezza, Teresa; Giaccari, Andrea

doi:10.2147/dddt.s114932

Cited by 83 publications

(61 citation statements)

References 59 publications

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“…The efficacy of combination therapy with ertugliflozin and sitagliptin observed in this study is consistent with that observed in other studies in the VERTIS program [ 18 , 19 ]. In the VERTIS FACTORIAL study, adding the combination of ertugliflozin (5 or 15 mg) and sitagliptin to the treatment of patients on metformin reduced HbA1c by 1.5% from a baseline of 8.6% (70 mmol/mol), which was superior to the effect of either agent alone [ 19 , 20 ]. In the present study, patients were not receiving background AHAs, and the mean baseline HbA1c of 8.9% was slightly higher than that in VERTIS FACTORIAL; the observed LS mean reductions from baseline in HbA1c for the E5/S100 and E15/S100 groups were slightly larger than those observed in the VERTIS FACTORIAL study (1.5% for both combination therapy groups).…”

Section: Discussionmentioning

confidence: 99%

“…In previous clinical studies, ertugliflozin used as a monotherapy [ 16 ], as an add on to metformin [ 17 ], as an add on to the combination of sitagliptin and metformin [ 18 ], and in combination with sitagliptin as an add on to metformin [ 19 , 20 ] improved glycemic control, reduced body weight, and generally reduced blood pressure with a low incidence of hypoglycemia. In other studies, sitagliptin used as a monotherapy [ 21 ] or as part of a dual therapy with metformin [ 22 ] also provided clinically meaningful reductions in blood glucose with a low risk of hypoglycemia or weight gain.…”

Section: Introductionmentioning

confidence: 99%

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Ertugliflozin and Sitagliptin Co-initiation in Patients with Type 2 Diabetes: The VERTIS SITA Randomized Study

Miller

Krumins

Zhou³

et al. 2018

Diabetes Ther

109

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IntroductionErtugliflozin is an oral sodium-glucose cotransporter 2 inhibitor that is being developed to treat type 2 diabetes mellitus (T2DM). This study assessed the efficacy and safety of co-initiation of ertugliflozin and sitagliptin compared with placebo in patients with T2DM inadequately controlled on diet and exercise.MethodsIn this phase III, randomized, double-blind, multicenter, placebo-controlled 26-week study (NCT02226003), patients with T2DM and glycated hemoglobin (HbA1c) 8.0–10.5% on diet/exercise were randomized 1:1:1 to ertugliflozin 5 mg once daily (QD) and sitagliptin 100 mg QD (E5/S100), ertugliflozin 15 mg QD and sitagliptin 100 mg QD (E15/S100), or placebo. The primary efficacy endpoint was the change from baseline in HbA1c at week 26.ResultsThe mean baseline HbA1c of the randomized patients (n = 291) was 8.9%. At week 26, both ertugliflozin/sitagliptin treatments provided significant reductions from baseline in HbA1c compared with placebo [least squares mean HbA1c change (95% confidence intervals) from baseline was − 0.4% (− 0.7, − 0.2), − 1.6% (− 1.8, − 1.4), and − 1.7% (− 1.9, − 1.5) for placebo, E5/S100, and E15/S100, respectively]. At week 26, 8.3%, 35.7%, and 31.3% of patients receiving placebo, E5/S100, and E15/S100, respectively, had HbA1c < 7.0%. Significant reductions in fasting plasma glucose, 2-h post-prandial glucose, body weight, and systolic blood pressure were observed with both ertugliflozin/sitagliptin groups compared with placebo. The incidence of adverse events (AEs) was similar across the groups. The incidences of the pre-specified AEs of urinary tract infection, genital mycotic infection, symptomatic hypoglycemia, and hypovolemia were low and not meaningfully different across groups.ConclusionCo-initiation of ertugliflozin with sitagliptin in patients with T2DM inadequately controlled on diet and exercise provided a clinically meaningful improvement in glycemic control over 26 weeks.Clinical Trial RegistrationClinicaltrials.gov NCT02226003.Electronic supplementary materialThe online version of this article (10.1007/s13300-017-0358-0) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Ertugliflozin and Sitagliptin Co-initiation in Patients with Type 2 Diabetes: The VERTIS SITA Randomized Study

Miller

Krumins

Zhou³

et al. 2018

Diabetes Ther

109

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“…The VERTIS CV trial will assess CV safety and efficacy of ertugliflozin in patients at high CV risk and will report in about 1 year. Adverse effect information is available from the product monograph (http://www.merck.ca/static/pdf/STEGLATRO-PM_E.pdf) and from a meta‐analysis of available phase 2/3 efficacy and safety data . Currently the risk profile appears to be similar to that observed with empagliflozin and dapagliflozin although a small increased risk of amputation has been reported.…”

Section: Introductionmentioning

confidence: 99%

A safety update on sodium glucose co‐transporter 2 inhibitors

Fitchett

2019

Diabetes Obesity Metabolism

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Sodium glucose co-transporter 2 inhibitors (SGLT2is) are the first class of glucose lowering agent to be shown to reduce cardiovascular events. They are generally well tolerated with infrequent serious adverse events. The most frequent side effect is genital mycotic infections with candida species that are usually mild to moderate in severity, easily treated and infrequently recur. Urinary tract infections, although common in patients with diabetes, have not been shown to be increased in controlled studies with SGLT2i. Hypoglycaemia can occur when an SGLT2i is added to agents that cause hypoglycaemia, such as insulin or sulphonylureas. Volume depletion and hypotension is infrequent and can be minimized by adjusting diuretic and antihypertensive treatment in patients at risk. Acute renal failure or kidney injury was observed in early observational studies. However, in randomized controlled trials (RCTs) and in more recent observational studies a decreased incidence of acute kidney injury was observed in SGLT2-treated patients compared to those receiving either placebo or another class of glucose lowering agents. An increased incidence of amputation (largely feet and toes) was observed in the RCT with canagliflozin but not with the other SGLT2i. Observational studies have shown either an increased risk of amputation with other agents whereas another study showed no increase. Although the increased risk of amputation is very low, avoidance of SGLT2i in patients at high risk seems prudent. Increased incidence of fractures was observed with canagliflozin but not with SGLT2i nor in a meta-analysis that included canagliflozin, empagliflozin and dapagliflozin. No increased incidence of cancer has been observed in either RCTs or observational studies. K E Y W O R D Scanagliflozin, dapagliflozin, diabetes, empagliflozin, ertugliflozin, SGLT2 inhibition

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“…Ertugliflozin is chemically (C22H25ClO7): 2 The molecular structure of Ertugliflozin is depicted in Figure 1. 2…”

Section: Chemical Structure Of Ertugliflozinmentioning

confidence: 99%

Ertugliflozin: a novel anti-diabetic drug

Sharma

Jaiswal

et al. 2018

Int J Basic Clin Pharmacol

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Diabetes Mellitus is a disorder of global proportion. Despite various treatment modalities presently being available, yet the desired glycaemic control and patient outcomes have not been achieved completely. Sodium glucose co-transporter type 2 inhibitors (SGLT2 inhibitors) are one such promising group of emerging drugs in diabetes treatment. Ertugliflozin prevents the reabsorption of glucose by inhibiting sodium-glucose cotransporter-2 (SGLT2) at proximal convoluted tubules. Ertugliflozin is available as 5mg and 15mg tablets. Ertugliflozin has been related to genital mycotic infections and urinary tract infections. Benefits of Ertugliflozin include better control on blood glucose, body weight and blood pressure.

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Spotlight on ertugliflozin and its potential in the treatment of type 2 diabetes: evidence to date

Cited by 83 publications

References 59 publications

Ertugliflozin and Sitagliptin Co-initiation in Patients with Type 2 Diabetes: The VERTIS SITA Randomized Study

Ertugliflozin and Sitagliptin Co-initiation in Patients with Type 2 Diabetes: The VERTIS SITA Randomized Study

A safety update on sodium glucose co‐transporter 2 inhibitors

Ertugliflozin: a novel anti-diabetic drug

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