What ADA consensus on hyperglycemia management has to say about DPP-4 inhibitors

USA: Early combination therapy with a DPP-4 inhibitor and metformin increases glycemic durability compared to a stepwise approach to therapy, according to a consensus update released by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD).

According to the report, Dipeptidyl peptidase-4 inhibitors (DPP-4 inhibitors) have a neutral effect on weight, are generally well tolerated, has intermediate glucose-lowering efficacy, and have minimal risk of hypoglycemia. Also, it has demonstrated cardiovascular safety.

The report by ADA and EASD on hyperglycemia management for type 2 daibetes was presented at the 58th EASD Annual Meeting in Stockholm, Sweden, and subsequently published in the journals Diabetologia and Diabetes Care.

DPP-4 inhibitors are oral medications that inhibit the enzyme inactivation of endogenous incretin hormones, leading to a decrease in glucagon secretion and glucose-dependent insulin release.

"Cardiovascular outcomes trials (CVOTs) have reported cardiovascular safety without a reduction in cardiovascular risk of four DPP-4i (alogliptin, saxagliptin, linagliptin, and sitagliptin)," the consensus update stated. "The Cardiovascular and Renal Microvascular Outcome Study With Linagliptin (CARMELINA) trial demonstrated a decrease in risk of albuminuria progression with linagliptin. With saxagliptin, an increased risk of hospitalization for heart failure (HHF) is noted. This increased HHF risk is also mentioned in its label. Also, there have been rare reports of hypersensitivity reactions and arthralgia with the DPP-4i class.

The report further suggests that DPP-4 inhibitor's modest efficacy and high tolerability mean that they are suited for specific populations and considerations. For instance, mean daily blood glucose was found to be similar with lesser hypoglycaemic events with linagliptin than insulin in a 6 month open-label RCT comparing a DPP-4i (linagliptin) with basal insulin (glargine) in long-term care and skilled nursing facilities.

In older adults with type 2 diabetes, treatment of inpatient hyperglycemia with basal insulin plus DPP4 inhibitors is shown to be safe and effective, with comparable mean daily blood glucose but fewer hypoglycaemic episodes and lower glycemic variability compared with the basal–bolus insulin regimen.

About DPP-4 inhibitors

Dipeptidyl peptidase 4 (DPP-4) inhibitors, also known as gliptins, are a group of oral medications approved by the FDA used for the treatment of type 2 diabetes in adults, which is a significant risk factor for heart failure, stroke, coronary disease, and many other cardiovascular condition.

FDA approved DPP-4 inhibitors include saxagliptin, sitagliptin, alogliptin, and linagliptin. Vildagliptin has still not received FDA approval but has the approval from the European Medicines Agency (EMA). The drugs act through incretin hormones, which are gut hormones responsible for glucose homeostasis after the intake of oral food.

Reference:

Davies, M.J., Aroda, V.R., Collins, B.S. et al. Management of hyperglycaemia in type 2 diabetes, 2022. A consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD). Diabetologia (2022). https://doi.org/10.1007/s00125-022-05787-2