A Novel, Long-Acting Agonist of Glucose-Dependent Insulinotropic Polypeptide Suitable for Once-Daily Administration in Type 2 Diabetes

2005 ◽  
Vol 314 (3) ◽  
pp. 1187-1194 ◽  
Author(s):  
Nigel Irwin ◽  
Brian D. Green ◽  
Mark H. Mooney ◽  
Brett Greer ◽  
Patrick Harriott ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Daily Administration ◽  
Once Daily ◽  
Long Acting ◽  
Acting Agonist

scholarly journals Once daily administration of the SGLT2 inhibitor, empagliflozin, attenuates markers of renal fibrosis without improving albuminuria in diabetic db/db mice

2016 ◽  
Vol 6 (1) ◽  
Author(s):  
Linda A. Gallo ◽  
Micheal S. Ward ◽  
Amelia K. Fotheringham ◽  
Aowen Zhuang ◽  
Danielle J. Borg ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Blood Glucose ◽  
Growth Factor ◽  
Kidney Disease ◽  
Sglt2 Inhibitor ◽  
Collagen Iv ◽  
Daily Administration ◽  
Once Daily ◽  
Glucose Lowering

Abstract Blood glucose control is the primary strategy to prevent complications in diabetes. At the onset of kidney disease, therapies that inhibit components of the renin angiotensin system (RAS) are also indicated, but these approaches are not wholly effective. Here, we show that once daily administration of the novel glucose lowering agent, empagliflozin, an SGLT2 inhibitor which targets the kidney to block glucose reabsorption, has the potential to improve kidney disease in type 2 diabetes. In male db/db mice, a 10-week treatment with empagliflozin attenuated the diabetes-induced upregulation of profibrotic gene markers, fibronectin and transforming-growth-factor-beta. Other molecular (collagen IV and connective tissue growth factor) and histological (tubulointerstitial total collagen and glomerular collagen IV accumulation) benefits were seen upon dual therapy with metformin. Albuminuria, urinary markers of tubule damage (kidney injury molecule-1, KIM-1 and neutrophil gelatinase-associated lipocalin, NGAL), kidney growth, and glomerulosclerosis, however, were not improved with empagliflozin or metformin, and plasma and intra-renal renin activity was enhanced with empagliflozin. In this model, blood glucose lowering with empagliflozin attenuated some molecular and histological markers of fibrosis but, as per treatment with metformin, did not provide complete renoprotection. Further research to refine the treatment regimen in type 2 diabetes and nephropathy is warranted.

Insulin Glargine: A New Basal Insulin

2002 ◽  
Vol 36 (6) ◽  
pp. 1019-1027 ◽  
Author(s):  
Terri L Levien ◽  
Danial E Baker ◽  
John R White ◽  
R Keith Campbell
Keyword(s):  
Type 2 Diabetes ◽  
Insulin Glargine ◽  
Basal Insulin ◽  
Nph Insulin ◽  
Once Daily ◽  
Nocturnal Hypoglycemia ◽  
Acting Insulin ◽  
Long Acting

OBJECTIVE: To review the pharmacology, pharmacokinetics, dosing guidelines, adverse effects, drug interactions, and clinical efficacy of insulin glargine. DATA SOURCES: Primary and review articles regarding insulin glargine were identified by MEDLINE search (1966–July 2001); abstracts were identified through Institute for Scientific Information Web of Science (1995–July 2001) and the American Diabetes Association. Additional information was obtained from the insulin glargine product information. STUDY SELECTION AND DATA EXTRACTION: All of the articles and meeting abstracts identified from the data sources were evaluated, and all information deemed relevant was included in this review. Priority was placed on data from the primary medical literature. DATA SYNTHESIS: Insulin glargine is a long-acting, recombinant human insulin analog that is given once daily as a basal source of insulin in patients with type 1 or type 2 diabetes mellitus. Modification of the basic insulin structure has produced a new insulin that is soluble at an acidic pH, but precipitates in the subcutaneous tissue and is slowly released from a depot. Insulin glargine has a slower onset of action than NPH insulin and a longer duration of action with no peak activity. Once-daily administration of insulin glargine has comparable efficacy to that of NPH insulin administered once or twice daily in basal-bolus regimens when used in combination with intermittent doses of regular insulin or insulin lispro in patients with type 1 and type 2 diabetes, and in conjunction with oral antidiabetic agents in patients with type 2 diabetes. Overall, insulin glargine has an incidence of hypoglycemia comparable to or less than that of NPH insulin, with a reduced incidence of nocturnal hypoglycemia compared with NPH insulin seen in some studies. CONCLUSIONS: Insulin glargine is a long-acting insulin analog capable of providing 24-hour basal insulin coverage when administered once daily at bedtime. Its activity profile, which lacks a pronounced peak, more closely resembles that of endogenous basal insulin than that of other intermediate- or long-acting insulins and appears more likely to be associated with a reduced incidence of hypoglycemia, particularly nocturnal hypoglycemia. Insulin glargine physiologically provides basal insulin but, for most patients, the addition of a rapid-acting insulin, like insulin lispro, before or with meals will need to be included in the treatment regimen to achieve optimal management of blood glucose concentrations.

scholarly journals Evolution of glucagon-like peptide-1 receptor agonists for the treatment of type 2 diabetes

2017 ◽  
Vol 20 (4) ◽  
pp. 286-298 ◽  
Author(s):  
Gagik R. Galstyan ◽  
Evgeniya A. Karataeva ◽  
Ekaterina A. Yudovich
Keyword(s):  
Type 2 Diabetes ◽  
Glycemic Control ◽  
Antidiabetic Drugs ◽  
Incretin Effect ◽  
Once Daily ◽  
Short Acting ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1 ◽  
Long Acting

Glucagon-like peptide-1 (GLP-1) receptor agonists (GLP-1RAs) are a class of antidiabetic drugs developed over the past 15 years. GLP-1, a gastrointestinal peptide hormone that contributes to the postprandial incretin effect, stimulates glucose-dependent insulin secretion. The incretin effect is greatly diminished in type 2 diabetes, but can be restored by GLP-1RAs. These drugs also exert other GLP-1 effects, including reducing glucagon secretion, delaying gastric emptying, reducing food intake, improving cardiac ventricular function, and lowering blood pressure. Short-acting GLP-1RAs are administered once daily (lixisenatide) or twice daily (exenatide); long-acting GLP 1RAs are administered once daily (liraglutide) or once weekly (slow-release exenatide, dulaglutide, albiglutide). All GLP-1RAs significantly reduce glycated hemoglobin (HbA1c) in patients with type 2 diabetes whose glycemic control is inadequate with oral antidiabetic drugs. Compared with other antidiabetic medications, GLP-1RAs provide better glycemic control with the additional benefit of weight loss. Within this class, long-acting GLP-1RAs are more efficacious than short-acting GLP-1RAs, with similar or lower risk of hypoglycemia and lower incidence of gastrointestinal adverse effects. Head-to-head trials and a network meta-analysis suggest that once daily liraglutide is the most effective GLP-1RA in reducing HbA1c. Dulaglutide is the only once-weekly GLP 1RA demonstrated to be noninferior to liraglutide. The once-weekly GLP-1RAs offer additional advantages to patients, including fewer injections and easy-to-use, single-dose pen devices. Despite the relatively recent development of GLP-1RAs, international diabetes guidelines recognize the benefits of this class of drugs and recommend them as a treatment option for patients with type 2 diabetes.

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