Medicina clinica
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Review
[Characteristics and types of GLP-1 receptor agonists. An opportunity for individualized therapy].
Glucagon-like peptide 1 (GLP-1) is secreted from enteroendocrine L-cells in response to oral nutrient intake and elicits glucose-stimulated insulin secretion while suppressing glucagon secretion. Moreover slows gastric emptying -reducing postprandial glycemic excursions-, reduces body weight, systolic blood pressure and has beneficial effects in the cardiovascular and central nervous systems. Since the 1990s, the efficacy of GLP-1 in reducing blood glucose levels in type 2 diabetes (DM2) was well known. ⋯ Hence, DPP-4 inhibitors -which increase pseudo-physiologically endogenous GLP-1 levels- were developed. In addition, several GLP-1 receptor agonists have been designed to avoid DPP-4-breakdown and/or rapid renal elimination and, therefore, induce a pharmacologic effect in the GLP-1 receptor: short-acting, long-acting, and prolonged-acting GLP-1 analogs. Each class has different structural, pharmacodynamic and clinical properties and could be administered in different therapeutical regimens giving us the opportunity to individualize the therapy of DM2.
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Modulation of the incretin effect has opened up a new strategy in the treatment of diabetes mellitus type 2 (DM2). To date, this physiological mechanism has been boosted in two ways: firstly, by pharmacological inhibition of the enzyme that physiologically degrades glucagon-like peptide-1 (GLP-1) receptor agonists, dipeptidyl peptidase-4 (DPP4); secondly, through the development of GLP-1 agonists (GLP-1a) that are resistant to the action of DPP-4. ⋯ On the other hand, this higher efficacy also seems to be associated with the higher rate of adverse effects associated with aGLP-1 therapy compared with DPP-4 inhibition. These and other differentiating characteristics of the two drug families will determine the choice of drug therapy in the personalized treatment of hyperglycemia in patients with DM2.
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Systemic lupus erythematosus (SLE) is a complex disease with different clinical forms of presentation, including a wide range of severity and organic involvement. Such circumstance, along with the fact of the uncommon nature of the disease and the absence of clinically representative response criteria, make it difficult to design controlled clinical trials in SLE patients. As a result, observational studies have a special relevance, being a source of valuable information of SLE prognosis and outcome as well as of the efficacy and adverse effects of the different therapies. ⋯ Although clinical trials have not confirmed a clear superiority of rituximab in SLE, observational studies have shown good response rates in severe SLE manifestations or refractory forms. Belimumab has recently been added to the therapeutic armamentarium of SLE; although its place in clinical practice is not well-defined, it may be recommended in active patients with no response or good tolerance to standard therapies. Hydroxichloroquine improves survival, decreases the risk of thrombosis and flares and is safe in pregnancy, and should be considered the baseline therapy in most SLE patients.