An overview of new GLP-1 receptor agonists for type 2 diabetes

Abstract

The new GLP-1RAs may have the benefit of requiring less frequent subcutaneous dosing or being active by oral administration. However, cardiovascular outcome trials have shown that DPP4 inhibitors are neutral for cardiovascular events and the first cardiovascular outcome trial with lixisenatide reported similar results, whereas the trial with the SGLT2 inhibitor empagliflozin showed a reduction in cardiovascular events. These findings in patients with high cardiovascular risk may favor the use of SGLT2 inhibitors as a second line treatment after metformin but there should still be an important role for novel GLP-1RAs, especially when weight reduction is required.

ZB-16, a Novel GPR119 Agonist, Relieves the Severity of Streptozotocin–Nicotinamide-Induced Diabetes in Rats

“…Short lifetime of native GLP-1 was a reason for the development of several long-lasting analogs with twice daily (exenatide), once daily (lixisenatide and liraglutide), and once weekly (exenatide ER, albiglutide, and dulaglutide) injection that have been approved for use in the US. GLP-1 receptor agonists are effective enough; however, the main disadvantage of these medications is that they have only injectable forms that are less convenient than oral administration for patients with type 2 diabetes mellitus (2). Alternative approach is to inhibit the enzyme DPP-4 that inactivates native GLP-1.…”

Effects of glucose-lowering drugs on cardiovascular outcomes in patients with type 2 diabetes

“…Compared with the placebo-treated group, the lixisenatide-treated group had greater average reductions in HbA1c of 0.27%, reductions of body weight of 0.7 kg, reductions in systolic blood pressure (SBP) of 0.8 mmHg, but an increase in heart rate of 0.4 beats/minute. Lixisenatide has a short half-life (3-4 h) and duration of action and when given once daily the effects on HbA1c, body weight and SBP are less than with the longer acting GLP-1 agonists [13]. This may have contributed to the neutral outcome in the ELIXA study.…”

“…The SGLT2 inhibitors are generally well tolerated but do have the side effects of increased genital mycotic infections, urinary tract infections, and volume depletion and the rare occurrence of ketoacidosis, and with some of the drugs a possible risk of bone fractures and acute kidney injury. The currently available GLP-1 agonists require subcutaneous injection and frequently cause gastrointestinal side effects [13]. It may be fortuitous that liraglutide showed an advantage in patients with renal impairment [9] as the SGLT2 inhibitors are contraindicated in patients with renal impairment of greater than moderate degree.…”

Neuroprotective properties of incretin mimetics in brain ischemia and neurodegenerative diseases

“…Более десятка аналогов ГПП-1 и низкомо-лекулярных агонистов рецептора ГПП-1 (ГПП-1Р) проходят клинические испытания в настоящее вре-мя. Основные направления при разработке новых аналогов ГПП-1 связаны с увеличением интервалов между инъекциями от 1 (Semaglutide, Glymera) до 2 и 4 нед (ITCA 650, Efpeglenatide, VRS 859) и создани-ем пероральных форм (NN9924, NN9926, NN9927, TTP054, TTP273, ZYOG1, ARI-1732TS) [9,10]. На стадии доклинических исследований находятся мо-лекулы, обладающие агонистическим действием к нескольким инкретиновым рецепторам (к ГПП-1, ГПП-2, ГИП и др.)…”

“…На стадии доклинических исследований находятся мо-лекулы, обладающие агонистическим действием к нескольким инкретиновым рецепторам (к ГПП-1, ГПП-2, ГИП и др.) [9].…”