Review compares effectiveness, cost, and safety of second-line drugs for diabetes

The review found that sulfonylureas were more cost-effective than newer agents, but an ACP Journal Club commentary stressed the importance of shared decision making in the choice of a second agent.


A review compared second-line therapies for type 2 diabetes, including sulfonylureas (SULs), insulin, dipeptidyl peptidase-4 inhibitors, glucagon-like peptide-1 analogues, sodium-glucose cotransporter-2 (SGLT-2) inhibitors, meglitinide, alpha-glucosidase inhibitors, and thiazolidinediones. It found that SULs were the most cost-effective but increased risk for severe hypoglycemia and that SGLT-2 inhibitors seemed to be superior in terms of all-cause mortality.

The review was published in May 2017 by the Canadian Agency for Drugs and Technologies in Health. The following commentary by Natalia Genere, MD, and Victor M. Montori, MD, MSc, FACP, was published in the ACP Journal Club section of the Jan. 16 Annals of Internal Medicine.

Wells and colleagues' high-quality systematic review and network meta-analysis estimated the relative effectiveness, safety, and cost-effectiveness of newer second-line drugs. It would be a mistake to conclude from this review that patients should necessarily be offered the most cost-effective sequence—metformin followed by SULs. Cost-effectiveness analyses may not fully consider the costs of hospitalization for severe hypoglycemia (higher risk with insulin and SULs) or diabetic ketoacidosis (reported as a possible complication of using SGLT-2 inhibitors) and almost always assume savings from reducing the risk for diabetes complications despite evidence that these may have been overestimated. These analyses also may not account for the loss in quality of life associated with the burden of treatment due to administration, self-monitoring, and mild hypoglycemia, which affects many users of SULs or insulin.

Rather than an opportunity to create a policy based on tiers or algorithms, the selection of antihyperglycemic drugs is best done by shared decision making, in which the patient's situation must be addressed by 1 of the available alternatives. No algorithm can replace the conversation through which patients and clinicians determine the option that makes intellectual, emotional, and practical sense for the patient. Patients and clinicians must embark on this work by drawing, for now, from limited evidence about the comparative effects of available antihyperglycemic agents on the quality and duration of the patient's life, beyond their ability to reduce HbA1c levels.