Single-dose administration of sevelamer eliminated bile acid-mediated GLP-1 secretion in patients with type 2 diabetes, which could be explained by reduced bile acid stimulation of the basolaterally localized TGR5 on enteroendocrine L cells.
Metformin elicited an enhancement of the GLP-1 response to cholecystokinin-induced gallbladder emptying in patients with type 2 diabetes, whereas no derived effects on insulin or glucagon secretion were evident in this acute setting.
A large proportion of patients with type 1 diabetes do not reach their glycaemic target of glycated hemoglobin (HbA1c) <7.0% (53 mmol/mol) and, furthermore, an increasing number of patients with type 1 diabetes are overweight and obese. Treatment of type 1 diabetes is based on insulin therapy, which is associated with well-described and unfortunate adverse effects such as hypoglycaemia and increased body weight. Glucagon-like peptide-1 (GLP-1) receptor agonists (RAs) are the focus of increasing interest as a possible adjunctive treatment to insulin in type 1 diabetes because of their glucagonostatic and extrapancreatic effects. So far, the focus has mainly been on the long-acting GLP-1RAs, but the risk-benefit ratio emerging from studies evaluating the effect of long-acting GLP-1RAs as adjunctive therapy to insulin therapy in patients with type 1 diabetes has been disappointing. This might be attributable to a lack of glucagonostatic effect of these long-acting GLP-1RAs in type 1 diabetes, alongside development of tachyphylaxis to GLP-1-induced retardation of gastric emptying. In contrast, the shortacting GLP-1RAs seem to have a preserved and sustained effect on glucagon secretion and gastric emptying in patients with type 1 diabetes, which could translate into effective lowering of postprandial glucose excursions; however, these observations regarding short-acting GLP1RAs are all derived from small open-label trials and should thus be interpreted with caution. In the present paper we review the potential role of GLP-1RAs, in particular short-acting GLP1RAs, as add-on to insulin in the treatment of type 1 diabetes.
K E Y W O R D Santidiabetic drug, GLP-1 analogue, glucagon, incretin therapy, insulin therapy, type 1 diabetes
| INTRODUCTIONTreatment of type 1 diabetes is based on insulin therapy with the goal of achieving glycated haemoglobin (HbA1c) concentration <7.0% (53 mmol/mol) to prevent micro-and macrovascular complications; however, only 13% to 19% of patients with type 1 diabetes succeed in meeting this glycaemic target.1-4 Additionally, hypoglycaemic events resulting from insulin therapy remain a serious adverse effect and might lead to both physical and psychological morbidity and mortality. 5 Insulin therapy has also been reported to result in a body weight increase, and an estimated 50% of patients with type 1 diabetes in the industrialized part of the world are now overweight or obese, with reports of 25% also having metabolic syndrome.
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