Treatment of Type 1 Diabetic Patients with Glucagon-Like Peptide-1 (GLP-1) and GLP-1R Agonists

Abstract

GLP-1 (glucagon-like peptide-1) is a peptide hormone secreted from endocrine cells in the intestinal mucosa in response to meals. The major effects of GLP-1 are to increase glucose-induced insulin secretion and reduce glucagon release, but GLP-1 also inhibits gastric emptying rate and reduces appetite and bodyweight in obese subjects. In vivo studies using animal models of type 2 diabetes and in vitro studies using human islet cells have suggested that GLP-1 or GLP-1 analogues are also able to increase beta-cell mass, but in animal models of type 1 diabetes, there is much less evidence for a beta-cell preserving effect. This review summarizes the present knowledge of GLP-1 and its analogues regarding its role as a possible treatment in patients with type 1 diabetes. The studies that address the effect of GLP-1 and GLP-1 analogues on beta-cell mass in both type 2 and type 1 diabetes, as well as the potential of GLP-1 as an adjuvant therapy in islet cell transplantation, will be reviewed. Suggestions for future studies of GLP-1 treatment in type 1 diabetes may include early treatment in order to preserve beta-cell mass and prolong the remission period, but should also take a potential insulin sparing effect and changes in the risk of hypoglycemia into account.

Deletion of GαZ Protein Protects against Diet-induced Glucose Intolerance via Expansion of β-Cell Mass

“…The link between the loss of ␤-cell mass in both T1DM and late stage T2DM has provided a rationale for testing T2DM treatments that act through cAMP generation in rodent models of T1DM and in human T1DM patients and pancreatic islet transplant recipients. These studies show prolonged survival, improved glycemia, and maintenance of graft function for a longer duration (52)(53)(54). Therapeutic strategies that increase islet cell cAMP production, such as those that based on the G␣ z pathway described in this manuscript, could be an important tool in T1DM therapy.…”

Semaglutide seems to be more effective the other GLP-1Ras

“…This effect might be expected to reduce or halt the progression of type 2 diabetes, but the findings in this regard are unclear (13). In one study, beta cell function was evaluated after three years of treatment with high doses of a short acting GLP-1 RA (exenatide), and during this period there was no deterioration, but the same was true in the control group subjected to intensive insulin therapy (14), suggesting that both approaches may be protective.…”

Adjuvant Liraglutide and Insulin Versus Insulin Monotherapy in the Closed-Loop System in Type 1 Diabetes

“…However, in patients with some preservation of beta-cell function (which is about 10% in patients with type 1 diabetes) the endogenous insulin secretion may also be affected by liraglutide. 26,27 One limitation is the lack of participant and investigator blinding. However, blinding would have been difficult due to gastrointestinal side effects and ease of the liraglutide dosing pen.…”