Patient considerations in the management of type 2 diabetes - critical appraisal of dapagliflozin.

Type 2 diabetes affects more than 350 million people worldwide, and its prevalence is increasing. Many patients with diabetes do not achieve and/or maintain glycemic targets, despite therapy implementation and escalation. Multiple therapeutic classes of agents are available for the treatment of type 2 diabetes, and the armamentarium has expanded significantly in the past decade. Selective sodium glucose co-transporter 2 inhibitors, including dapagliflozin, represent the latest development in pharmacologic treatment options for type 2 diabetes. This class has a unique mechanism of action, working by increasing glucose excretion in the urine. The insulin-independent mechanism results in decreased serum glucose, without hypoglycemia or weight gain. Dapagliflozin is a once-daily oral therapy. Expanding therapy options for a complex patient population is critical, and dapagliflozin has a distinct niche that can be a viable option for select patients with diabetes.

Treatment of IgA nephropathy: an update.

OBJECTIVE: To review current literature regarding treatment options for immunoglobulin A nephropathy (IgAN). DATA SOURCES: A MEDLINE search was performed using the terms IgA nephropathy, Berger's disease, immunoglobulin A nephropathy, angiotensin converting enzyme inhibitors, angiotensin II receptor blockers, fish oil, omega-3 fatty acids, statins, hydroxymethylglutaryl-CoA reductase inhibitors, immunosuppressive therapy, corticosteroids, mycophenolate mofetil, cyclophosphamide, cyclosporine, azathioprine, leflunomide, antiplatelets, anticoagulants, vitamin E, infliximab, calcitriol, and intravenous immunoglobulins. A date limit was not set; however, focus was on publications from 1999 to June 2011 to review recent literature and therapeutic recommendations. STUDY SELECTION AND DATA EXTRACTION: All articles in English, including studies conducted in humans, meta-analyses, review articles, guidelines, statements, and reference citations, were identified and evaluated. DATA SYNTHESIS: IgAN is the most common primary glomerulonephritis worldwide, leading to end-stage renal disease in 20-30% of patients. Evidence guiding management of IgAN has been sparse and clinical trials have not conclusively demonstrated effective treatments, largely due to suboptimal methodologies. Treatment strategies have included management of blood pressure and lipids, improvement or stabilization of kidney function, and reduction of proteinuria. This review of IgAN provides an update regarding standard and nonconventional treatment options based on recently published literature. CONCLUSIONS: Supportive therapies, including angiotensin blockade, should be considered as first-line therapy for patients with urine protein >0.5 g/day and/or blood pressure >140/90 mm Hg. Corticosteroids could be considered as add-on or monotherapy for patients with urine protein >1 g/day with preserved renal function. Conclusive data are lacking for general treatment recommendations for the use of other therapies for IgAN.

Dapagliflozin for the treatment of type 2 diabetes.

OBJECTIVE: To review the literature and describe the pharmacology, pharmacokinetics, clinical safety, and efficacy of dapagliflozin, a compound currently in Phase 3 clinical trials. DATA SOURCES: A search of the literature was conducted via MEDLINE (1995-March 2009) and ClinicalTrials.gov using the search terms dapagliflozin, SGLT2 inhibitor, sodium-glucose co-transport inhibition, and renal glucose reabsorption inhibition. Bibliographies of identified articles were also used to identify useful references. STUDY SELECTION AND DATA EXTRACTION: All English-language reports evaluating dapagliflozin were included in this review, including abstracts and scientific presentations. DATA SYNTHESIS: Due to the increasing prevalence of type 2 diabetes, suboptimal management of the associated hyperglycemia, morbidity and mortality associated with the disease, and the limitations of currently available therapies, novel therapeutic strategies are needed for its treatment. Dapagliflozin represents the first selective, sodium-glucose cotransporter 2 inhibitor that functions by regulating renal glucose reabsorption. Clinical trial data are limited, but available evidence supports clinically significant reductions in fasting plasma glucose, postprandial plasma glucose, hemoglobin A(1c), and body weight with this agent. In addition, dapagliflozin has demonstrated excellent tolerability with safety data demonstrated in both Phase 1 and Phase 2 studies. CONCLUSIONS: Dapagliflozin represents the first in a new class of drugs that may represent a promising new option in the treatment of type 2 diabetes. Results of ongoing Phase 3 clinical trials are necessary to demonstrate efficacy and safety of this agent across various patient populations and clinical scenarios.