The ‘collateral benefits‘ of noninsulin therapies for Type 2 diabetes

Abstract

Newer noninsulin agents to treat Type 2 diabetes offer more options for treatment intensification.Recent guidelines continue to emphasize a stepwise approach after metformin monotherapy is exhausted.When efficacy is essentially equivalent between agents, the 'collateral' effects of noninsulin agents can help clinicians craft diabetic treatments to suit patients' needs and comorbid conditions. Concerns about possible detrimental cardiovascular effects from sulfonylureas and thiazolidiones make incretin-based therapies (DPP-4 inhibitors and GLP-1 mimetics) more attractive in patients with risk factors.Thiazolidinediones increase fluid retention, which may promote decompensated congestive heart failure and diabetic macular edema in at-risk patients.In women with polycystic ovarian syndrome, metformin improves ovulation rates, hyperandrogenemia and hirsutism, but is generally less efficacious in achieving pregnancy compared with ovarian stimulation with clomiphene.Long-term use of pioglitazone has been linked to increased risk of bladder cancer in epidemiological studies; however, the mechanism remains unknown. Pancreatic cancer, meanwhile, has not been definitively linked with the use of exenatide or sitagliptin. Finally, thyroid C-cell hyperplasia and metaplasia have been observed in rodents treated with liraglutide; however, increased rates of medullary thyroid cancer have not been detected in patients treated with GLP-1 mimetics. SUMMARYThe increasing availability of non-insulin-based pharmacological therapy for Type 2 diabetes permits clinicians greater flexibility to design treatment regimens that suit individual patients' needs. Often, patients with Type 2 diabetes carry multiple comorbidities related to insulin resistance and inadequate diabetic control, which predispose to the