Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0042963 (vomiting)
 31,883 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Currently, six glucagon-like peptide-1 receptor agonists (GLP-1RAs) are approved for treating type 2 diabetes. These fall into two classes based on their receptor activation: short-acting exenatide twice daily and lixisenatide once daily; and longer-acting liraglutide once daily, exenatide once weekly, albiglutide once weekly and dulaglutide once weekly. The phase III trial of a seventh GLP-1RA, taspoglutide once weekly, was stopped because of unacceptable adverse events (AEs). Nine phase III head-to-head trials and one large phase II study have compared the efficacy and safety of these seven GLP-1RAs. All trials were associated with notable reductions in glycated haemoglobin (HbA1c) levels, although liraglutide led to greater decreases than exenatide formulations and albiglutide, and HbA1c reductions did not differ between liraglutide and dulaglutide. As the short-acting GLP-1RAs delay gastric emptying, they have greater effects on postprandial glucose levels than the longer-acting agents, whereas the longer-acting compounds reduced plasma glucose throughout the 24-h period studied. Liraglutide was associated with weight reductions similar to those with exenatide twice daily but greater than those with exenatide once weekly, albiglutide and dulaglutide. The most frequently observed AEs with GLP-1RAs were gastrointestinal disorders, particularly nausea, vomiting and diarrhoea. Nauseaoccurred less frequently, however, with exenatide once weekly and albiglutide than exenatide twice daily and liraglutide. Both exenatide formulations and albiglutide may be associated with higher incidences of injection-site reactions than liraglutide and dulaglutide. GLP-1RA use in clinical practice should be customized for individual patients, based on clinical profile and patient preference. Ongoing assessments of novel GLP-1RAs and delivery methods may further expand future treatment options.
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PMID:Review of head-to-head comparisons of glucagon-like peptide-1 receptor agonists. 2651 Nov 2

Gastrointestinal (GI) adverse events (AEs) are the most frequently reported treatment-related AEs associated with glucagon-like peptide-1 receptor agonists (GLP-1RAs) in the treatment of type 2 diabetes mellitus. The GI safety of albiglutide, a once-weekly GLP-1RA, was assessed using data from five phase III studies. In a pooled analysis of four placebo-controlled trials, the most common GI AEs were diarrhoea (albiglutide, 14.5% vs. placebo, 11.5%) and nausea (albiglutide, 11.9% vs. placebo, 10.3%), with most patients experiencing 1-2 events. The majority were mild or moderate in intensity and their median duration was 3-4 days. Vomiting occurred in 4.9% of patients in the albiglutide vs. 2.6% in the placebo group. For both albiglutide and placebo, serious GI AEs (2.0% vs. 1.5%) and withdrawals attributable to GI AEs (1.7% vs. 1.5%) were low. In a 32-week trial of albiglutide 50 mg weekly versus liraglutide 1.8 mg daily, nausea occurred in 9.9% of patients in the albiglutide group vs. 29.2% in the liraglutide group. Vomiting occurred in 5.0% in the albiglutide vs. 9.3% in the liraglutide group. In conclusion, albiglutide has an acceptable GI tolerability profile, with nausea and vomiting rates slightly higher than those for placebo but lower than those for liraglutide.
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PMID:Gastrointestinal safety across the albiglutide development programme. 2709 71

Glucagon-like peptide 1 receptor agonists (GLP-1RA) are the newest treatment for diabetes mellitus (DM). These drugs can down-regulate fasting glucose more than oral drugs and lead to more constant glucose levels compared to regular insulin. Acute pancreatitis is a serious condition that may have a fatal outcome. It has been shown that long term and high doses of GLP-1RA can cause pancreatic changes in animals, but no connection has been proven in humans. We present the case of a 67 years old man with DM treated with oral drugs for 10 years until 3 months before, when GLP-1RA was added. He presented progressive abdominal pain, vomiting, and increased level of serum lipase and amylase were found. Ultrasonography and computed tomography found pancreatic and peripancreatic fatty tissue inflammation (inflammation score 2, necrosis score 0). All the etiologies of acute pancreatitis (lithiasis, alcohol, autoimmune, or trauma) were excluded. After GLP-1RA cessation and supportive treatment the evolution was self-limited with full recovery within 5 days. We concluded that acute pancreatitis can be considered a side effect of the GLP-1 treatment.
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PMID:Acute pancreatitis during GLP-1 receptor agonist treatment. A case report. 2944 Sep 61

The incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) are released from enteroendocrine cells in response to the presence of nutrients in the small intestines. These homones facilitate glucose regulation by stimulating insulin secretion in a glucose dependent manner while suppressing glucagon secretion. In patients with type 2 diabetes (T2DM), an impaired insulin response to GLP-1 and GIP contributes to hyperglycemia. Dipeptidyl peptidase-4 (DPP-4) inhibitors block the breakdown of GLP-1 and GIP to increase levels of the active hormones. In clinical trials, DPP-4 inhibitors have a modest impact on glycemic control. They are generally well-tolerated, weight neutral and do not increase the risk of hypoglycemia. GLP-1 receptor agonists (GLP-1 RA) are peptide derivatives of either exendin-4 or human GLP-1 designed to resist the activity of DPP-4 and therefore, have a prolonged half-life. In clinical trials, they have demonstrated superior efficacy to many oral antihyperglycemic drugs, improved weight loss and a low risk of hypoglycemia. However, GI adverse events, particularly nausea, vomiting, and diarrhea are seen. Both DPP-4 inhibitors and GLP-1 RAs have demonstrated safety in robust cardiovascular outcome trials, while several GLP-1 RAs have been shown to significantly reduce the risk of major adverse cardiovascular events in persons with T2DM with pre-existing cardiovascular disease (CVD). Several clinical trials have directly compared the efficacy and safety of DPP-4 inhibitors and GLP-1 RAs. These studies have generally demonstrated that the GLP-1 RA provided superior glycemic control and weight loss relative to the DPP-4 inhibitor. Both treatments were associated with a low and comparable incidence of hypoglycemia, but treatment with GLP-1 RAs were invariably associated with a higher incidence of GI adverse events. A few studies have evaluated switching patients from DPP-4 inhibitors to a GLP-1RA and, as expected, improved glycemic control and weight loss are seen following the switch. According to current clinical guidelines, GLP-1RA and DPP-4 inhibitors are both indicated for the glycemic management of patients with T2DM across the spectrum of disease. GLP-1RA may be preferred over DPP- 4 inhibitors for many patients because of the greater reductions in hemoglobin A1c and weight loss observed in the clinical trials. Among patients with preexisting CVD, GLP-1 receptor agonists with a proven cardiovascular benefit are indicated as add-on to metformin therapy.
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PMID:GLP-1 Analogs and DPP-4 Inhibitors in Type 2 Diabetes Therapy: Review of Head-to-Head Clinical Trials. 3230 45