Dose‐ranging efficacy and safety study of ertugliflozin, a sodium‐glucose co‐transporter 2 inhibitor, in patients with type 2 diabetes on a background of metformin

Amin, Neeta B.; Wang, X.; Jain, Sunil; Lee, D. S.; Nucci, Gianluca; Rusnak, James M.

doi:10.1111/dom.12460

Cited by 60 publications

(80 citation statements)

References 22 publications

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“…The outcomes of ongoing cardiovascular safety studies could further clarify the T2DM treatment algorithm, as could the introduction of additional long-acting GLP-1RAs, DPP-4 inhibitors and SGLT2 inhibitors that are in development 18,26,[353][354][355][356][357] .…”

Section: Treatment Algorithmmentioning

confidence: 99%

Pharmacology and therapeutic implications of current drugs for type 2 diabetes mellitus

2016

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Type 2 diabetes mellitus (T2DM) is a global epidemic that poses a major challenge to health-care systems. Improving metabolic control to approach normal glycaemia (where practical) greatly benefits long-term prognoses and justifies early, effective, sustained and safety-conscious intervention. Improvements in the understanding of the complex pathogenesis of T2DM have underpinned the development of glucose-lowering therapies with complementary mechanisms of action, which have expanded treatment options and facilitated individualized management strategies. Over the past decade, several new classes of glucose-lowering agents have been licensed, including glucagon-like peptide 1 receptor (GLP-1R) agonists, dipeptidyl peptidase 4 (DPP-4) inhibitors and sodium/glucose cotransporter 2 (SGLT2) inhibitors. These agents can be used individually or in combination with well-established treatments such as biguanides, sulfonylureas and thiazolidinediones. Although novel agents have potential advantages including low risk of hypoglycaemia and help with weight control, long-term safety has yet to be established. In this Review, we assess the pharmacokinetics, pharmacodynamics and safety profiles, including cardiovascular safety, of currently available therapies for management of hyperglycaemia in patients with T2DM within the context of disease pathogenesis and natural history. In addition, we briefly describe treatment algorithms for patients with T2DM and lessons from present therapies to inform the development of future therapies.

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Section: Treatment Algorithmmentioning

confidence: 99%

Pharmacology and therapeutic implications of current drugs for type 2 diabetes mellitus

2016

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“…SGLT2 inhibitors have been developed for the treatment of type 2 diabetes and a number are already available for clinical use [4][5][6][7][8][9]. Other SGLT2 inhibitors and dual SGLT2/SGLT1 inhibitors are being tested for the treatment of type 2 diabetes [10][11][12]. SGLT2 inhibitors lower fasting and postprandial glycaemia by enhancing urinary glucose excretion (UGE), a mechanism that is independent of insulin secretion [13].…”

Section: Introductionmentioning

confidence: 99%

Metabolic consequences of acute and chronic empagliflozin administration in treatment-naive and metformin pretreated patients with type 2 diabetes

et al. 2015

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Aims/hypothesis Sodium glucose co-transporter 2 (SGLT2) inhibitors lower glycaemia by inducing glycosuria, but raise endogenous glucose production (EGP). Metformin lowers glycaemia mainly by suppressing EGP. We compared the effects of the SGLT2 inhibitor empagliflozin in treatment-naive (TN) and metformin pretreated (Met) patients with type 2 diabetes. Methods A total of 32 TN and 34 patients on a stable dose of metformin, two subgroups of a study that we previously reported, received a mixed meal with double-tracer glucose administration and indirect calorimetry at baseline, after a single 25 mg dose of empagliflozin, and after 4 weeks of treatment with empagliflozin 25 mg/day. Results At baseline, compared with the TN group, the Met group had higher fasting glycaemia (9.1 ± 1.7 vs 8.2 ± 1.3 mmol/l), lower fasting and postmeal insulin secretion, lower beta cell glucose sensitivity (37 [18]

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“…Of these, 15 trials fulfilled our inclusion criteria and were selected in the meta-analysis [15][16][17][18][19][20][21][22][23][24][25][26][27][28][29] (Fig. 1).…”

Section: Study Characteristicsmentioning

confidence: 99%

“…1). Four studies contained two groups [16,19,20,25,27] and one study contained three groups except for DPP-4 inhibitors [25]. Outcomes of one study were assessed at two time-points, with two different comparators [22].…”

Section: Study Characteristicsmentioning

confidence: 99%

Effects of dipeptidyl peptidase-4 inhibitors on blood pressure in patients with type 2 diabetes

Zhang

Zhao

2016

Journal of Hypertension

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This review was undertaken to assess the effects of dipeptidyl peptidase-4 (DPP-4) inhibitors on blood pressure (BP) in patients with type 2 diabetes (T2DM). We searched three main databases (PubMed, Web of Science, and Scopus) for relevant articles. Randomized controlled trials which reported BP changes from baseline to study endpoint in patients with T2DM receiving treatment of DPP-4 inhibitors were included for analysis. Random effects models were used to measure the mean differences with 95% confidence intervals (CIs). Fifteen trials involving 5636 participants were identified. When compared with placebo or nontreatment, DPP-4 inhibitors achieved greater reductions for both SBP (mean difference, -3.04 mmHg; 95% CI, -4.37 to -1.72; P < 0.00001) and DBP (mean difference, -1.47 mmHg; 95% CI, -1.79 to -1.15; P < 0.00001). But the BP-lowering effects of sodium-glucose cotransporter 2 inhibitors were more significant than those of DPP-4 inhibitors for both SBP (mean difference, 4.44 mmHg; 95% CI, 2.67-6.22; P < 0.00001) and DBP (mean difference, 2.15 mmHg; 95% CI, 1.08-3.21; P < 0.00001). No significant differences in BP changes were shown between DPP-4 inhibitors with other antidiabetic agents including glucagon-like peptide 1 receptor agonists, pioglitazone, sulphonylureas, metformin, and α-glucosidase inhibitors. DPP-4 inhibitors may exert modest BP-lowering effects compared with placebo or nontreatment for patients with T2DM, but no significant BP improvement was seen with this drug class when compared with other antidiabetic medications.

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Dose‐ranging efficacy and safety study of ertugliflozin, a sodium‐glucose co‐transporter 2 inhibitor, in patients with type 2 diabetes on a background of metformin

Abstract: Ertugliflozin (1-25 mg/day) improved glycaemic control, body weight and blood pressure in patients with T2DM suboptimally controlled on metformin, and was well tolerated.

Cited by 60 publications

References 22 publications

Pharmacology and therapeutic implications of current drugs for type 2 diabetes mellitus

Pharmacology and therapeutic implications of current drugs for type 2 diabetes mellitus

Metabolic consequences of acute and chronic empagliflozin administration in treatment-naive and metformin pretreated patients with type 2 diabetes

Effects of dipeptidyl peptidase-4 inhibitors on blood pressure in patients with type 2 diabetes

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