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Pramlintide (Symlin®), a synthetic analog of a neurohormone amylin, was approved by the US Food and Drug Administration for use along with premeal insulin in patients with type 1. In patients with type 2 diabetes, pramlintide is approved for addition to premeal insulin in those patients who are either only on premeal insulin or those receiving the combination of insulin and metformin and/or a sulfonylurea. This article reviews the pharmacology, pharmacokinetics, dosing, clinical trials, safety, contraindications, and drug interactions of pramlintide therapy. A search for published clinical trials and therapeutic reviews in the English language was done in the following databases: Iowa Drug Information Service (1966 to July 2008), MEDLINE (1966 to July 2008), and International Pharmaceutical Abstracts (1970 to July 2008). Pramlintide and amylin were used as keywords and title words. References of key articles were also reviewed to identify additional publications. Amylin is a 37 amino acid peptide neurohormone cosecreted from the beta cells of the pancreas, along with insulin, in response to meals. Amylin lowers serum glucose by decreasing glucagon release, slowing gastric emptying and decreasing food intake. Pramlintide, a synthetic analog of amylin, reduces 2-hour postprandial blood glucose between 3.4 and 5 mmol/L, reduces A1C by 0.2% to 0.7% and has no effect on fasting glucose levels. The use of pramlintide was associated with up to a 1.6 kg weight loss. Nausea was the most commonly reported adverse event. Pramlintide is an amylin analog that was FDA approved for the treatment of type 1 and type 2 diabetes. Its use results in modest reduction of A1C and the most frequent side effects are hypoglycemia and nausea.

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Jobe LJ, Meléndez GC, Levick SP, Du Y, Brower GL, Janicki JS. TNF-␣ inhibition attenuates adverse myocardial remodeling in a rat model of volume overload. Am J Physiol Heart Circ Physiol 297: H1462-H1468, 2009. First published August 7, 2009 doi:10.1152/ajpheart.00442.2009.-Tumor necrosis factor (TNF)-␣ is a proinflammatory cytokine that has been implicated in the pathogenesis of heart failure. In contrast, we have recently shown that myocardial levels of TNF-␣ are acutely elevated in the aortocaval (AV) fistula model of heart failure. Based on these observations, we hypothesized that progression of adverse myocardial remodeling secondary to volume overload would be prevented by inhibition of TNF-␣ with etanercept. Furthermore, a principal objective of this study was to elucidate the effect of TNF-␣ inhibition during different phases of the myocardial remodeling process. Eight-week-old male Sprague-Dawley rats were randomly divided into the following three groups: sham-operated controls, untreated AV fistulas, and etanercept-treated AV fistulas. Each group was further subdivided to study three different time points consisting of 3 days, 3 wk, and 8 wk postfistula. Etanercept was administered subcutaneously at 1 mg/kg body wt. Etanercept prevented collagen degradation at 3 days and significantly attenuated the decrease in collagen at 8 wk postfistula. Although TNF-␣ antagonism did not prevent the initial ventricular dilatation at 3 wk postfistula, etanercept was effective at significantly attenuating the subsequent ventricular hypertrophy, dilatation, and increased compliance at 8 wk postfistula. These positive adaptations achieved with etanercept administration translated into significant functional improvements. At a cellular level, etanercept also markedly attenuated increases in cardiomyocyte length, width, and area at 8 wk postfistula. These observations demonstrate that TNF-␣ has a pivotal role in adverse myocardial remodeling and that treatment with etanercept can attenuate the progression to heart failure. diastolic function; intrinsic contractility; myocyte dimensions; etanercept; extracellular matrix; ventricular pressure-volume relationship THE PROINFLAMMATORY CYTOKINE tumor necrosis factor-␣ (TNF-␣) has been documented to elicit a variety of responses in the heart ranging from cardioprotective to pathological (3,4,14,23,(32)(33)(34). However, chronically elevated levels of TNF-␣ have been identified as a risk factor for coronary heart disease and congestive heart failure (12,22,23). Consistent with this, Bozkurt et al. (3) demonstrated that a chronic infusion of rats with pathological levels of TNF-␣ was sufficient to induce myocardial remodeling consisting of left ventricular (LV) wall thinning, dilatation, and collagen degradation, resulting in reduced myocardial function. Furthermore, collagen degradation due to increased matrix metalloproteinase (MMP) activity and a reduction in tissue inhibitor of metalloproteinases-1 (TIMP-1) in mice with cardiac-restricted overexpression of TNF-␣ has been imp...

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There is a higher prevalence of low testosterone levels in males with type 2 diabetes compared to those without. Additionally, there is evidence that low testosterone levels may predict the development of type 2 diabetes. Symptoms of hypogonadism include decreased libido, decreased bone mineral density (BMD), and decreased lean muscle mass. The majority of the published cases in men with diabetes were attributed to age-related idiopathic hypogonadotropic hypogonadism. This paper reviews the link between type 2 diabetes and age-related hypogonadism and the treatment options for hypogonadism. Pharmacists who provide care for males with diabetes should be aware of the increased incidence of hypogonadism, know how to screen for it, and be able to recommend appropriate therapy.