Changing the approach to type 2 diabetes treatment: A comparison of glucagon-like peptide-1 receptor agonists and sulphonylureas across the continuum of care

Abstract

Despite the importance of individualised strategies for patients with type 2 diabetes mellitus (T2DM) and the availability of alternative treatments, including glucagon-like peptide-1 receptor agonists (GLP-1 RAs), sulphonylureas are still widely used in practice. Clinical evidence shows that GLP-1 RAs may provide better and more durable glycaemic control than sulphonylureas, with lower risk of hypoglycaemia. Other reported benefits of GLP-1 RAs include weight loss rather than weight gain (as observed with sulphonylureas), blood pressure reduction and improvement in lipid profiles. In general, the main adverse events with GLP-1 RAs are gastrointestinal in nature. The respective modes of action of GLP-1 RAs and sulphonylureas contribute to differences in the durability of glycaemic control (related to effects on beta-cells) and effects on body weight. Moreover, the glucose-dependent mode of action of GLP-1 RAs, which favours a low incidence of hypoglycaemia, contrasts with the glucose-independent mode of action of sulphonylureas. Evidence from cardiovascular outcomes trials indicates a consistent finding of cardiovascular safety across the GLP-1 RAs and suggests a class benefit for the long-acting GLP-1 RAs in reducing three-point major adverse cardiovascular events, cardiovascular mortality and all-cause mortality. In contrast, potential concerns relating to an increased incidence of adverse cardiovascular events with sulphonylureas have yet to be fully resolved. Recent updates to management guidelines recommend that treatment selection for patients with T2DM should consider clinical trial evidence of cardiovascular safety. Available evidence suggests that this selection should give preference to GLP-1 RAs over sulphonylureas, especially for patients at high cardiovascular risk.

Keywords: GLP-1 RAs; cardiovascular safety; durability; glycaemic control; hypoglycaemia; sulphonylureas.

FIGURE 1

Results for a mixed‐treatment comparison meta‐analysis for sulphonylureas, glucagon‐like peptide‐1 receptor agonists and other non‐insulin glucose‐lowering drugs. Reproduced with permission from Phung et al. HbA1c goal <7% (53 mmol/mol). The squares represent the pooled effect size for each class of oral glucose‐lowering drug. Error bars represent 95% credible intervals. The number of trials included in each mixed‐treatment comparison analysis is as follows: A = 26 trials, B = 13 trials, C = 15 trials and D = 24 trials. AGI, alpha‐glucosidase inhibitor; DPP‐4, dipeptidyl peptidase‐4; GLP‐1, glucagon‐like peptide‐1; HbA1c, glycated haemoglobin; SU, sulphonylurea; TZD, thiazolidinediones. To convert changes in HbA1c % values to mmol/mol: HbA1c value/0.09148.

FIGURE 2

Sulphonylureas were associated with a significantly increased risk of cardiovascular mortality., , , , , , Adapted with permission from Phung et al.