Oral antidiabetes agents for the management of inpatient hyperglycaemia: so far, yet so close

Abstract

Background Hyperglycaemia is an ongoing challenge in hospital settings and is associated with poor outcomes. Current recommendations for the management of inpatient hyperglycaemia suggest insulin as the main glucose-lowering treatment choice and limit the administration of oral antidiabetes agents to a small proportion of cases because of safety concerns. Aim To present and critically appraise the available evidence on the use of oral antidiabetes agents in the hospital setting and the risk-benefit balance of such an approach in the era of cardiovascular outcomes trials. Methods PubMed, Embase and Google Scholar databases were searched to identify relevant published work. Available evidence on the efficacy and the safety profile of oral agents in the context of their use in hospitalized individuals are summarized and discussed in this narrative review. Results There is no robust evidence to suggest the use of metformin, thiazolidinediones, sulfonylureas and sodium-glucose co-transporter-2 inhibitors in the hospital setting, although some of their effects on acute outcomes deserve further evaluation in future studies. However, the use of dipeptidyl peptidase-4 inhibitors in inpatients with type 2 diabetes is supported by a few, well-designed, randomized controlled trials. These trials have demonstrated good safety and tolerability profiles, comparable to insulin glucose-lowering efficacy, and a reduction in insulin dose when dipeptidyl peptidase-4 inhibitors are co-administered with insulin, in individuals with mild to moderate hyperglycaemia and a stable clinical condition. Conclusion The administration of dipeptidyl peptidase-4 inhibitors to specific groups of inpatients might be a safe and effective alternative to insulin.

Basal-Bolus Insulin Regimen for Hospitalised Patients with COVID-19 and Diabetes Mellitus: A Practical Approach

“…In such cases, the patient should be kept under close watch for hypoglycaemia, and an adjustment in insulin dose should be considered. The use of oral dipeptidyl peptidase-4 (DPP-4) inhibitors has also been reported to be a safe and effective treatment in patients with mild to moderate hyperglycaemia and in stable clinical condition, and a reduction of insulin dose may be needed in situations where these agents are co-administered with insulin [43]. The use or continuation of glucoselowering oral drugs other than DPP-4 inhibitors is generally not recommended for acutely ill patients with COVID-19 due to the potential for abrupt deterioration in clinical status [44].…”

The role of autoimmunity in the pathophysiology of type 2 diabetes: Looking at the other side of the moon

“…94 Side effects of the class mainly include negative effects on bone density, fluid retention, and cause of edema that might destabilize patients with heart and renal failure, whereas the CV safety of rosiglitazone has been debated. 95 Another class of oral glucose-lowering agents, dipeptidyl peptidase-4 (DPP-4) inhibitors, is known to exert immunomodulatory actions and has the potential to improve glycemic control and preserve β-cell mass in autoimmune diabetes. 78,79 Animal research has demonstrated that linagliptin prevents the autoimmune β-cell destruction and improves lumphocyte insulinitis in nonobese diabetic mice.…”

“…Specific agents within the class (saxagliptin and alogliptin), though, have been linked to an increased risk of hospitalization for HF. 95 In a post hoc analysis of the REWIND clinical program, treatment with the GLP-1 RA dulaglutide reduced HbA1c levels in positive GADA individuals. 100 Although the reduction was greater among those with low GADA titers, efficacy was also evident in GADA high patients.…”

“…GLP-1 RAs might cause gastrointestinal (GI) side effects, including diarrhea and vomiting, which could result in the discontinuation of therapy in a small proportion of patients under treatment with these agents. 95 Active β-cells produce high amounts of insulin, which result in increased antigen expression that renders β-cells vulnerable to immune-mediated injury. Exogenous insulin administration and subsequent β-cell rest and decreased antigen expression downregulate the potency of T-cells against immunological targets.…”

“…108 Although generally safe, biguanides might induce GI side effects and have been liked to an extremely rare, but potentially fatal, clinical entity, which is lactic acidosis. 95 Glyburide, a sulfonylurea, was shown to suppress islet amyloid polypeptide-mediated IL-1β production in vitro. 109 Sulfonylureas provoke weight gain and can cause severe and prolonged hypoglycemia; moreover, their CV safety has been questioned.…”