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Dapagliflozin for the treatment of type 2 diabetes: a review of the literature.

ABSTRACT: Dapagliflozin was the first drug in a class of therapies that took a new approach to glycemic control in adults with type 2 diabetes (T2D). It is an inhibitor of the sodium glucose cotransporter, resident in the proximal nephron, which is responsible for the recovery of filtered glucose back into circulation. Inhibiting this cotransporter reduces glucose recovery, increases glucose excretion, and reduces hyperglycemia. Here, we review some of the literature relating to the action, efficacy, and clinical use of dapagliflozin.A Medline search was conducted within date, animal, and language limits, and relevant papers were selected for review. Conference proceedings were reviewed to obtain up-to-date literature on this drug. Clinical trial websites were reviewed for ongoing studies.On average, treatment with dapagliflozin results in improvement in glycated hemoglobin by 0.50%, fasting plasma glucose by 1 mmol/L, weight by 2 kg, body mass index by 1.1%, and systolic/diastolic blood pressure by 4/2 mmHg over 24-52 weeks. The weight benefit is greater when used in association with sulfonylureas. It is generally well tolerated, but comes with an increased risk of genitourinary and urinary tract infections. In addition, it is associated with reversible changes to renal function that need to be explored. Early reports of an association with cancer also need to be carefully monitored.Dapagliflozin is a useful therapy for adult patients with T2D. It also holds potential for a broader range of patients with T2D (such as the elderly and pediatric populations), as well as those with other forms of diabetes, such as type 1 diabetes. While longer-term outcome studies of safety and efficacy are awaited, dapagliflozin forms a very useful and welcome addition to our armamentarium for managing patients with T2D.

SUBMITTER: Saeed MA

PROVIDER: S-EPMC4267514 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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Dapagliflozin for the treatment of type 2 diabetes: a review of the literature.

Saeed Mujahid A MA Narendran Parth P

Drug design, development and therapy 20141210

<h4>Objective</h4>Dapagliflozin was the first drug in a class of therapies that took a new approach to glycemic control in adults with type 2 diabetes (T2D). It is an inhibitor of the sodium glucose cotransporter, resident in the proximal nephron, which is responsible for the recovery of filtered glucose back into circulation. Inhibiting this cotransporter reduces glucose recovery, increases glucose excretion, and reduces hyperglycemia. Here, we review some of the literature relating to the acti ...[more]

PMID: 25525338

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Project description:BACKGROUND:To compare the first-in-class sodium glucose co-transporter 2 (SGLT2) inhibitor, dapagliflozin, with existing type 2 diabetes mellitus (T2DM) treatment options available within the European Union (EU) for add-on therapy to sulfonylureas (SUs). METHODS:A systematic review was conducted to identify randomised controlled trials (RCTs) in T2DM patients inadequately controlled by SU monotherapy. Direct meta-analysis, Bucher indirect comparisons and Bayesian network meta-analysis (NMA) were conducted on studies meeting predefined inclusion criteria. Sufficient data were available to assess three clinical endpoints at 24 (+/- 6) weeks follow-up: mean change in HbA1c from baseline, mean change in weight from baseline, and the proportion of patients experiencing at least one episode of hypoglycaemia. The effect of confounding baseline factors was explored through covariate analyses. RESULTS:The search identified 1,901 unique citations, with 1,870 excluded based on title/abstract. From reviewing full-texts of the remaining 31 articles, 5 studies were considered eligible for analysis. All studies were comparable in terms of baseline characteristics, including: HbA1c, age and body mass index (BMI). In addition to dapagliflozin, sufficient data for meta-analysis was available for three dipeptidyl peptidase-4 (DPP-4) inhibitors and one glucagon-like peptide-1 (GLP-1) analogue. Based on fixed-effect NMA, all treatment classes resulted in statistically significant decreases in HbA1c at follow-up compared to placebo. Dapagliflozin treatment resulted in significantly decreased weight at follow-up compared to placebo (-1.54 kg; 95% CrI -2.16, -0.92), in contrast to treatment with GLP-1 analogues (-0.65 kg; 95% CrI -1.37, 0.07) and DPP-4 inhibitors (0.57 kg; 95% CrI 0.09, 1.06). The odds of hypoglycaemia were similar to placebo for dapagliflozin and DPP-4 inhibitor add-on treatment, but significantly greater than placebo for GLP-1 analogue add-on treatment (10.89; 95% CrI 4.24, 38.28). Assessment of NMA model heterogeneity was hindered by the small size of the network. CONCLUSIONS:Dapagliflozin, DPP-4 inhibitors and GLP-1 analogues, in combination with SU, all provided better short-term glycaemic control compared to SU monotherapy. Dapagliflozin was the only add-on therapy that had both a favourable weight and hypoglycaemia profile compared to the other classes of treatment evaluated.

Project description:IntroductionIn clinical trials, liraglutide has proven to be an effective drug for the treatment of type 2 diabetes mellitus (T2DM). The real-world effectiveness of liraglutide has been investigated in numerous studies. The aim of this systematic literature review is to collate evidence on the real-world clinical effectiveness of liraglutide.MethodsA review of publications from Medline, EMBASE, the Cochrane Library, and conference proceedings was conducted to identify observational studies that assessed the clinical effectiveness of liraglutide in real-world clinical practice. This review was conducted according to the National Institute of Health and Care Excellence (NICE) guidance. No language or time limits were applied, except to the conference proceedings (2013-2015). Endpoints for data extraction were decided a priori. Study quality appraisal was done for full-text journal articles.ResultsOf 124 publications included in the review, 43 were full-text articles. Liraglutide significantly reduces glycated hemoglobin (HbA1c) within 6 months of initiating treatment (mean change in HbA1c from baseline: -0.9% to -2.2%; HbA1c <7.0%: 29.5-65.0%). The NICE composite endpoint (HbA1c reduction ≥1% and weight reduction ≥3%) was met in 16.9-47.0% of patients with liraglutide treatment. Liraglutide therapy led to a mean change in absolute weight from baseline of -1.3 to -8.65 kg. Liraglutide treatment was well tolerated in patients with T2DM. The rate of occurrence of hypoglycemia with liraglutide monotherapy was ≤0.8%. Hypoglycemia was more common in patients taking antidiabetic medications (0.0-15.2%) together with liraglutide. The beneficial glycemic and weight effect of liraglutide therapy in patients with T2DM was maintained for at least 12 months.ConclusionEvidence from observational studies reflecting real-world clinical practice demonstrates that liraglutide therapy improves glycemic control with a low risk of hypoglycemia, and is associated with significant weight loss in patients with T2DM. These observations are consistent with clinical trial findings.FundingNovo Nordisk A/S, Søborg, Denmark.

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Dapagliflozin for the treatment of type 2 diabetes: a review of the literature.

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Dapagliflozin for the treatment of type 2 diabetes: a review of the literature.

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