Careful use to minimize adverse events of oral antidiabetic medications in the elderly

ABSTRACT

Introduction

An increasing number of older patients has type 2 diabetes treated with different oral antidiabetic agents whose safety may raise concern considering some particularities of a heterogeneous elderly population.

Areas covered

This article discusses some characteristics of older patients that could increase the risk of adverse events, with a focus on hypoglycemia. It describes the most frequent and/or severe complications reported in the elderly in both randomized controlled trials and observational studies with metformin, sulfonylureas, meglitinides, alpha-glucosidase inhibitors, thiazolidinediones, dipeptidyl peptidase-4 inhibitors (gliptins) and sodium-glucose cotransporter type 2 inhibitors (gliflozins).

Expert opinion

Old patients may present comorbidities (renal impairment, vascular disease, heart failure, risk of dehydration, osteoporosis, cognitive dysfunction) that could increase the risk of severe adverse events. Sulfonylureas (and meglitinides) induce hypoglycemia, which may be associated with falls/fractures and cardiovascular events. Medications lacking hypoglycemia should be preferred. Gliptins appear to have the best tolerance/safety profile whereas gliflozins exert a cardiorenal protection. However, data are lacking in very old or frailty old patients so that caution and appropriate supervision of such patients are required. Taking advantage of a large choice of pharmacotherapies, personalized treatment is recommended based upon both drug safety profiles and old patient individual characteristics.

KEYWORDS:

• Antidiabetic agents
• elderly
• hypoglycemia
• individualized therapy
• safety
• type 2 diabetes

Article Highlights

• Most older persons combine clinical characteristics that could increase the risk of adverse events associated with glucose-lowering agents

• Given the heterogeneity of older patients with T2D, an individualised pharmacological approach is warranted to maximise the safety profile

• Hypoglycemia should be avoided in older patients (risk of fall, cardiovascular complications and cognitive dysfunction) so that drugs that stimulate insulin secretion (SUs, meglitinides) should be used with caution.

• Metformin may remain the first-line glucose-lowering agent in elderly people provided that contra-indications are respected (yet less restrictions in recent years).

• The safety/tolerance profile of DPP-4is appears excellent so that this pharmacological class is a good option in the elderly population with T2D

• Given the increasing interest for SGLT2is and because of some concerns about their safety, more dedicated studies are warranted to delineate their benefit/risk balance in the elderly population.

Declaration of interest

AJ Scheen has received lecturer/advisor fees from AstraZeneca, Boehringer Ingelheim, Eli Lilly and Company, Janssen Pharmaceuticals, Merck Sharp & Dohme, Novartis, NovoNordisk, Sanofi and Servier. He also worked as clinical investigator in several cardiovascular outcome trials (PROactive, TECOS, EMPA-REG OUTCOME, CANVAS-R, DECLARE-TIMI 58, LEADER, HARMONY OUTCOMES). He has no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Reviewer Disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.