Postgraduate medicine
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Postgraduate medicine · Oct 2014
ReviewSafety and efficacy of dulaglutide, a once weekly GLP-1 receptor agonist, for the management of type 2 diabetes.
Type 2 diabetes (T2D) is an increasingly common endocrine disorder that is characterized by chronic hyperglycemia and tissue compartment abnormalities, including macrovascular and microvascular complications. More than 90% of patients with T2D will be diagnosed and treated in the primary care setting. One of the relatively recent additions to the increasing array of approved antidiabetic medications is the glucagon-like peptide-1 receptor agonist class. Mechanisms of action for glucagon-like peptide-1 receptor agonists include: 1) stimulation of insulin secretion through β-cells, though only when glucose levels are elevated (hence, minimizing risk for hypoglycemia); 2) blunting of glucagon secretion; 3) increased satiety; and 4) decreased rate of release of gastric contents into the small intestine, thereby reducing glycemic load. Recent T2D treatment guidelines encourage individualization of therapy. Many patients still do not achieve optimal glycemic control. Therefore, other treatment options are important. ⋯ A literature search was performed using PubMed and MEDSCAPE to retrieve abstracts and articles pertinent to topics discussed in this review. Original research articles, reviews, and clinical trial manuscripts were identified based on relevance. Only English language articles were considered. Results In 3 phase 3 registration trials in patients with T2D, once-weekly dulaglutide demonstrated superior efficacy at the primary endpoint to metformin as monotherapy, to sitagliptin as add-on to metformin, and to exenatide twice daily as add-on to metformin and pioglitazone. The safety profile of dulaglutide in these trials is similar to currently available glucagon-like peptide-1 receptor agonists, characterized predominantly by gastrointestinal symptoms (ie, nausea, vomiting, and diarrhea). Based on these results, once-weekly dulaglutide should be a relevant additional treatment option for the management of T2D.
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Postgraduate medicine · Oct 2014
Randomized Controlled TrialSafety and efficacy of lorcaserin: a combined analysis of the BLOOM and BLOSSOM trials.
Lorcaserin, a novel selective 5-HT2C receptor agonist, is approved by the US Food and Drug Administration (FDA) for weight management in combination with lifestyle modification for adults with obesity and adults with overweight and ≥ 1 weight-related comorbid condition. The safety and effectiveness of lorcaserin in adult patients without type 2 diabetes mellitus was established based on 2 phase III clinical trials of similar design: Behavioral Modification and Lorcaserin for Overweight and Obesity Management (BLOOM) and Behavioral Modification and Lorcaserin Second Study for Obesity Management (BLOSSOM). This report presents a prespecified analysis of pooled data from these trials. ⋯ This pooled analysis of the phase III BLOOM and BLOSSOM trials shows that lorcaserin 10 mg twice daily, in combination with diet and exercise, is safe and tolerable, and is associated with statistically significant weight loss and clinically relevant improvements in cardiometabolic parameters.
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Postgraduate medicine · Oct 2014
ReviewSodium glucose co-transporter 2 inhibitors and their mechanism for improving glycemia in patients with type 2 diabetes.
Most antihyperglycemic agents available for the treatment of type 2 diabetes mellitus (T2DM) have insulin-dependent mechanisms of action; that is, they either stimulate insulin production (sulfonylureas, glinides, incretin mimetics, dipeptidyl peptidase-4 inhibitors), improve insulin sensitivity (thiazolidinediones, biguanides), or directly augment endogenous insulin (basal and prandial insulins). As β-cell function deteriorates, combination therapy is usually needed to effectively control glycemia. Moreover, some antihyperglycemic agents are associated with adverse effects, such as weight gain and hypoglycemia. ⋯ Canagliflozin and dapagliflozin are generally well tolerated, with a low risk of hypoglycemia when not used in combination with insulin and/or sulfonylurea. Higher incidences of genital mycotic infections and adverse events related to osmotic diuresis and volume depletion were observed with both agents; they were generally mild or moderate and infrequently led to study discontinuation. Based on current evidence, SGLT2 inhibitors provide an important new treatment option for patients with T2DM.
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Postgraduate medicine · Oct 2014
ReviewDelirium superimposed on dementia and mild cognitive impairment.
Dementia is an illness that progressively affects cognition, emotion, and functional status. It can be complicated by delirium, an acute disturbance of consciousness and cognition that develops over a short course with fluctuating symptoms. Patients with dementia who experience delirium tend to have slower resolution of symptoms, more adverse events, and poorer outcomes. ⋯ The main focus of treatment and management of delirium should be on prevention, which can be achieved through assessing patients for predisposing and precipitating factors. If a patient does develop delirium, a reassessment of precipitating factors is the first step in treatment, and then nonpharmacologic or pharmacologic treatment can be considered. The use of antipsychotics or melatonin to treat delirium in dementia is considered off-label.