GLP-1 Receptor Agonists and SGLT2 Inhibitors Among the Hottest Advances in the Field of Anti-Hyperglycemia

Physicians now have 13 different classes of drugs available to manage their patients’ hyperglycemia. The evolution of these drugs has occurred very rapidly over the last 20 years. Speaking at the 2014 Cardiometabolic Health Congress on Friday in Boston, John B. Buse, MD, PhD, Chief of the Division of Endocrinology at the University of North Carolina School of Medicine, updated attendees on the newest drugs and safety data available.

Within the past year, the European Medicines Agency concluded that patients taking insulin glargine are not at increased risk for developing breast cancer.

Secondary failure is still a major issue to consider when prescribing drugs in the sulfonylurea class, which include glipizide, glimepiride, and repaglinide. Patients taking sulfonylureas typically loose glycemic control more quickly than other anti-hyperglycemic agents.

Two significant issues were highlighted related to metformin therapy. It is becoming evident that patients taking metformin have an increased risk of a developing a vitamin B12 deficiency. In one study, compared to a placebo group, patients taking metformin had a 7.2% higher absolute risk of being deficient in vitamin B12 over 4.5 years. New recommendations were made in Europe and China for metformin use in patients with elevated creatinine levels. The updated recommendation is to avoid prescribing metformin for patients with stage 4 or 5 chronic kidney disease, and to proceed with caution in patients with stage 3 disease. Though the official information has not changed in the US, Buse indicated that physicians should consider adopting these prescribing guidelines for metformin.

Drugs in the thiazolidinedione (TZD) class achieve excellent long-term glycemic control by preventing beta-cell failure. While this is a very attractive feature of TZD agents, they have been associated with an increased risk of bone fractures in an observational study. A recent press release indicated that the primary analysis in an observational study of showed no association between the use of pioglitazone and the risk of bladder cancer over a 10-year follow-up period.

Glucagon-like peptide-1 (GLP-1) receptor agonists are among the hottest class of anti-hyperglycemia medications right now. Recent developments have made many of these agents available as once weekly doses. Buse presented data in press that showed that GLP-1 receptor agonists had nominally greater reductions in HbA1c levels than insulin glargine.

Forthcoming results from the DUAL-1 clinical trial of IDegLira, a combination of insulin degludec and liraglutide, showed a reduction in average HbA1c levels to 6.4% at 26 weeks of therapy.

The most recent addition to anti-hyperglycemia medications is the class ofsodium-glucose cotransporter 2 (SGLT2) inhibitors. Thus far, this class of medications is as effective as any oral agent at reducing HbA1c levels. Patients taking SGLT2 agents exhibit a modest weight loss of ~3kg after 26 weeks of therapy and a modest reduction in blood pressure. Side effects of SGLT2 inhibitors include genital mycotic infections for men and women and pollakiuria. Physicians should take note of the different dosing guidelines as it relates to the estimated glomerular filtration rate of patients.

Buse urged physicians to engage in shared decision making with the patient regarding which drug or combined regimen is the best. Many issues play into the patient’s decision -- including cost of the therapy, number of injections, and weight loss or gain -- that may not be immediately evident to the physician.