At the American Diabetes Association (ADA) 74th Scientific Sessions in June the healthcare community received inspiring news about the DPP-4 inhibitor Januvia (Sitagliptin). Many clinicians like myself would like to recommend an effective oral medication therapy for diabetes that will be successful in the management of diabetes. I always find myself weighing the need for aggressive initial treatment with oral therapy against the potential of hypoglycemia.

Januvia is indicated, as an adjunct to diet and exercise to improve glycemic control in adults with type 2 diabetes. 

A post-hoc analysis of a clinical trial, “A Phase III, Multicenter, Randomized, Double-Blind, Placebo-Controlled Clinical Trial to Study the Safety and Insulin-Sparing Efficacy of the Addition of Januvia in Patients With Type 2 Diabetes Mellitus Who Have Inadequate Glycemic Control on Insulin Alone or in Combination With Metformin,” revealed more information about nocturnal hypoglycemia. The study was conducted over 24 weeks in 660 insulin-treated patients, randomized to the addition of either Januvia 100 mg once-daily (n=329) or placebo (n=329) to their insulin regimen. What is different about the information provided at the ADA 74th Scientific Sessions is that previous data was reported for patients that took Januvia once daily with a stable dose of long-acting, intermediate-acting or premixed insulin. In contrast, the analyses being presented at ADA were in patients who underwent intensification of insulin therapy after initiation of Januvia.
 The post-hoc analysis measured the incidence of symptomatic nocturnal hypoglycemic episodes and showed that at 24 weeks:

  • Incident of symptomatic nocturnal hypoglycemic episodes (defined as events which occurred between 11 p.m. and 7 a.m.): Januvia vs. placebo group (14.9% vs. 20.1%; p=0.0812).  
  • The total number of reported nocturnal events: Januvia group vs. placebo group (110 vs. 216).
  • Patient achieving A1c<7%: Januvia achieved an hemoglobin A1c (A1C) <7.0%  without nocturnal hypoglycemia vs. placebo group (33.9% vs. 16.6%; p<0.0001).

In addition to the news about reduction of nocturnal hypoglycemia in patient on Januvia on intensified dose of basal or premixed insulin, a  Late-Breaking Observational data presented during the Scientific Sessions provided an insight about different oral treatment regimens and their possible effect on initiation of insulin. When it comes to choosing a medication regimen for type 2 patients, we need to remember that diabetes is a progressive disease, so that over time many patients may need to add insulin to their treatment regimens to improve glycemic control. If your patients are like mine, many of them rather postpone going on insulin so the success of an oral regimen is very important.  

 The study “Assessing time to insulin use among type 2 diabetes patients treated with sitagliptin or sulfonylurea plus metformin dual therapy” (169-LB) was a retrospective cohort study included patients with type 2 who used Januvia (n=3,864) or a sulfonylurea (n=3,864) as dual add-on therapy to metformin for at least 90 days after starting the second medication from 2006-2013. 

The results of the study were as follows:

  • The percentages of patients initiating insulin by years one through six were 3.6, 8.4, 12.9, 17.7, 22.4, 26.6 for patients taking Januvia (sitagliptin) vs. 4.1, 9.4, 14.6, 21.0, 27.1, 34.1 for patients taking a sulfonylurea.
  • Patients taking Januvia progressed more slowly to insulin use than patients taking a sulfonylurea (p=0.0034).
  • Januvia group by year 6 were 24% less likely to initiate insulin during the observation period vs. patients taking a sulfonylurea (HR = 0.76;p= 0.0011)
  • Progression to initiation of insulin
  • Slower progression in patients with a baseline A1C<9%; no statistically significant difference in progression time in patients with a baseline A1C>9%

The information that was presented at the Scientific Sessions regarding this DPP-4 inhibitor brings into light the benefits incretin based therapies can provide type 2 patients. According to algorithm recommended by ADA and the American College of Endocrinology, patients are to be started on oral medication regimen if A1C<9%. An effective oral regimen that has the potential to slow progression to initiation of insulin may be preferred by many patients. Also, less risk for nocturnal hypoglycemia with an oral medication regimen boosts my confidence in using a DPP-4 inhibitor medication in elderly patients or in other patients with potentially high risk for nocturnal hypoglycemia.