The Impact of Comorbidities on the Pharmacological Management of Type 2 Diabetes Mellitus

Diabetes mellitus affects over 20% of people aged > 65 years. With the population of older people living with diabetes growing, the condition may be only one of a number of significant comorbidities that increases the complexity of their care, reduces functional status and inhibits their ability to self-care. Coexisting comorbidities may compete for the attention of the patient and their healthcare team, and therapies to manage comorbidities may adversely affect a person's diabetes. The presence of renal or liver disease reduces the types of antihyperglycemic therapies available for use. As a result, insulin and sulfonylurea-based therapies may have to be used, but with caution. There may be a growing role for sodium-glucose co-transporter 2 (SGLT-2) inhibitors in diabetic renal disease and for glucagon-like peptide (GLP)-1 therapy in renal and liver disease (nonalcoholic steatohepatitis). Cancer treatments pose considerable challenges in glucose therapy, especially the use of cyclical chemotherapy or glucocorticoids, and cyclical antihyperglycemic regimens may be required. Clinical trials of glucose lowering show reductions in microvascular and, to a lesser extent, cardiovascular complications of diabetes, but these benefits take many years to accrue, and evidence specifically in older people is lacking. Guidelines recognize that clinicians managing patients with type 2 diabetes mellitus need to be mindful of comorbidity, particularly the risks of hypoglycemia, and ensure that patient-centered therapeutic management of diabetes is offered. Targets for glucose control need to be carefully considered in the context of comorbidity, life expectancy, quality of life, and patient wishes and expectations. This review discusses the role of chronic kidney disease, chronic liver disease, cancer, severe mental illness, ischemic heart disease, and frailty as comorbidities in the therapeutic management of hyperglycemia in patients with type 2 diabetes mellitus.