Clinical Briefs

By Louis Kuritzky, MD, Clinical Assistant Professor, University of Florida, Gainesville. Dr. Kuritzky is a consultant for GlaxoSmithKline and is on the speaker's bureau of GlaxoSmithKline, 3M, Wyeth-Ayerst, Pfizer, Novartis, Bristol-Myers Squibb, AstraZeneca, Jones Pharma, and Boehringer Ingelheim.

Oral Prednisolone for Acute Gout

There have been no major therapeutic steps added for the management of acute gouty arthritis (AGA) for over 30 years. Although extensive experience with NSAIDs and colchicine attests to their efficacy, recent recognition of important toxicities with both has stimulated interest in alternative interventions.

Corticosteroids (CTS)—oral, parenteral, or intra-articular—have shown efficacy in AGA. However, the comparative efficacy of CTS vs NSAIDs or colchicines is unknown, and was the subject of investigation by Nanssens, et al.

In a randomized controlled trial, 120 AGA subjects (confirmed by identification of urate crystals) were assigned to either 5 days of naproxen 500 mg bid (NAP) or prednisolone 35 mg qd (PRED); to make blinding secure, a double-dummy design, wherein PRED recipients received a matching placebo to provide b.i.d. dosing for both groups, was employed.

Four days into treatment, the results for pain reduction were essentially equivalent for PRED and NAP. There were no major adverse effects reported by either treatment group. Prednisolone 35 mg/d may be a reasonable alternative therapy for gout, especially when concerns about NSAID or colchicine toxicity are present.

Janssens H, et al. Lancet. 2008;371:1854-1860.

Adding Aliskiren to Losartan for Diabetic Nephropathy

Treatment with angiotensin receptor blockers (ARBs) reduces levels of proteinuria in diabetics, and forestalls endstage renal disease. Unfortunately, despite full therapeutic doses of either ARB or angiotensin converting enzyme inhibitors (ACEi), not all patients enjoy equal success in reducing renal protein losses. Combination therapies for proteinuria, such as ACEi + ARB or ACEi + spironolactone, offer promise in this regard, but the combination of the direct renin inhibitor aliskiren (ALIS) with ARB has not been previously investigated.

A population of type 2 diabetics with nephropathy (24 hr urine protein > 300 mg) was randomized to stabilization on losartan 100 mg/d plus either aliskiren titrated to 300 mg/d or placebo. Patients with nephrotic syndrome or severe chronic kidney disease (GFR <30) were excluded.

At six months, ALIS treatment produced a 20% greater reduction in the urinary albumin-to-creatinine ratio than placebo. Although BP reduction is also associated with reduced renal protein loss, correction for the modest BP effect of adding ALIS to ARB (2/1 mm Hg) still indicated a statistically significant, BP-independent impact. Adverse effects were similar in both treatment groups. Simultaneous modulation of the renin-angiotensin-aldosterone system by more than one mechanism provides additional benefit for reduction of proteinuria.

Parving HH, et al. N Engl J Med. 2008;358:2433-2446.

Early Aggressive Therapy in Type 2 Diabetes Pays Off

Using current criteria for the diagnosis of type 2 diabetes (DM2), approximately 50% of beta-cell function has been lost at the time of initial diagnosis. DM2 has been characterized as a disease of progressive decline in beta cell function; the UKPDS trial showed that all treatment regimens (sulfonylurea, metformin, insulin) were associated with progressive decline in control of A1c.

Because pancreatic beta cells become dysfunctional when subjected to persistent supraphysiologic glucose levels (perhaps as low as 140 mg/dL, sustained), investigators have opined that prompt intensive control of glucose might rejuvenate dysfunctional beta cells; limited data supports this concept.

Weng, et al performed a clinical trial on DM2 patients (n=382) comparing intensive insulin regimens (IIR) to oral hypoglycemic agents. Intensive insulin was either multiple daily insulin injections (basal insulin plus thrice daily insulin analog injections) or continuous subcutaneous insulin infusion.

Most IIR patients achieved glycemic control within 6 days, compared to 9.3 days using oral agents. All regimens were continued for 2 weeks once control was attained, and then discontinued, after which subjects used diet and exercise to try and maintain control for 1 year.

At one year, remission rates for IIR groups (45-50%) were statistically greater than oral agent rates (27%). First phase insulin response was improved only by IIR. Early intensive treatment produces durable improvements in beta cell function.

Weng J, et al. Lancet. 2008;371:1753-1760.