RESUMO
Continuously reducing excess blood glucose is a primary goal for the management of type 2 diabetes (T2D). Most patients with T2D require glucose-lowering medications to achieve and maintain adequate glycemic control; however, treatment failure may occur, limiting treatment options. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are an emerging therapeutic class that can be prescribed for patients instead of basal insulin after the failure of oral therapies. Recent studies have focused on the durability and tolerability of long-term GLP-1RA therapy. This review summarizes the key efficacy and safety findings from prospective phase 3 clinical studies of at least 76 weeks' duration for the GLP-1RAs currently approved in the United States and the European Union (albiglutide, dulaglutide, exenatide twice daily [BID], exenatide once weekly [QW], liraglutide, and lixisenatide). Currently, most of the long-term data are from uncontrolled extension studies, and continuous patient benefit has been observed for up to 3 years with multiple GLP-1RAs. Four-year comparative data demonstrated a longer time to treatment failure for exenatide BID than for sulfonylurea, and 3-year comparative extension data demonstrated greater glycated hemoglobin (HbA1c) reductions and weight loss with exenatide QW than with insulin glargine. Currently, the longest extension study for a GLP-1RA is the DURATION-1 study of exenatide QW, with >7 years of clinical data available. Data from DURATION-1 demonstrated that continuous HbA1c reductions and weight loss were observed for the patients continuing on the treatment, with no unexpected adverse events. Taken together, these data support GLP-1RAs as a long-term noninsulin treatment option after the failure of oral therapies.
RESUMO
BACKGROUND: Radioiodine is the treatment of choice for relapsed hyperthyroidism although the optimum protocol is uncertain. Fixed dose radioiodine is increasingly popular but responses may vary. AIM: To assess the outcome of 131I therapy in hyperthyroidism using a standard dose regimen in a regional referral centre and to explore factors influencing outcome. METHODS: We studied 449 patients (M:F 82:367; age range 13-89 y, median 42 y) with hyperthyroidism treated between 2003 and 2007 with a standard dose of 550 MBq 131I. Patients were classified as either Graves' disease, toxic multinodular goitre or indeterminate aetiology. Antithyroid drugs were routinely stopped at least 1 week before radioiodine. RESULTS: One year after radioiodine 334 (74%) were hypothyroid, 85 (19%) were euthyroid and 30 (7%) had required a further dose of 131I. Patients with Graves' disease were more likely to become hypothyroid than those with toxic multinodular goitre (78% v 37%, p<0.001) and less likely to become euthyroid (11% v 55%, p<0.001). Free T4 >80 pmol/L (normal range 9.0 - 19.0 pmol/L) at presentation was associated with an increased failure rate (17% compared with 5% and 3% for 40-79 pmol/L and <40 pmol/L respectively; p=0.01). Patients with either a small or no goitre were more likely to be successfully treated by a single dose (96%) than those with a medium/large goitre (85%, p<0.001). Anti-thyroid medication was taken by 345 (77%) (carbimazole n=319) patients up to 1 week prior to 131I and was associated with an increased failure rate (8% v 2%, p=0.027) compared to those who had not had antithyroid medication. Logistic regression showed free T4 at presentation to be the only independent risk factor for failure of the first dose of radioiodine (OR 2.5; 95% CI, 1.2-5.1, p=0.012). CONCLUSION: A single standard dose of 550 MBq 131I is highly effective in treating hyperthyroidism. The aetiology, severity of hyperthyroidism at diagnosis, goitre size and prior antithyroid medication all had a significant effect on outcome.