Up-Titration Strategy After DPP-4 Inhibitor-Based Oral Therapy for Type 2 Diabetes: A Randomized Controlled Trial Shifting to a Single-Dose GLP-1 Enhancer Versus Adding a Variable Basal Insulin Algorithm

Abstract

IntroductionIt is unclear whether adding basal insulin or enhancing incretin signaling with a glucagon-like peptide-1 receptor agonist (GLP-1RA) is more effective as an up-titration strategy after dipeptidyl peptidase-4 inhibitor (DPP-4i)-based oral antidiabetic drug (OAD) therapy. GLP-1RAs can be injected without dose adjustment, unlike basal insulin. Our objective was to examine the efficacy of changing patients inadequately controlled with oral DPP-4i-based OAD therapy to injectable GLP-1RA and discontinuing the DPP4i versus adding basal insulin glargine (IGlar) with the continuation of the oral DPP4i.MethodsSixty patients with type 2 diabetes (T2DM) and glycated hemoglobin (HbA1c) between 7.0% and 10.0% on DPP-4i-based OAD therapy were randomized to either adding IGlar and remaining on the DPP-4i or liraglutide and discontinuing the DPP-4i for 24 weeks. Patients in the IGlar group started with 0.1 unit/kg and were titrated according to the algorithm. In the liraglutide group, the DPP-4i was replaced with liraglutide 0.9 mg/day, the maximum dose in Japan. We evaluated HbA1c, glycated albumin (GA), and anthropometrics.ResultsHbA1c was significantly lower at week 24 (− 1.0 ± 0.9% in the IGlar group and − 0.6 ± 0.8% in the liraglutide group), but the difference between groups was not significant. Changes in GA were similar (− 2.9 ± 3.2% vs. − 2.6 ± 3.2%) in both groups. Body weight (BW) was significantly lower only in the liraglutide group (+ 0.5 ± 2.6 kg vs. − 2.2 ± 2.0 kg). The rate of minor hypoglycemic episodes was similar for both groups.ConclusionFor poorly controlled T2DM on DPP-4i-based OAD therapy, switching to single-dose liraglutide to enhance incretin signaling is as effective as dose-titrated basal IGlar, but significant BW reduction was only seen in the liraglutide group. These results suggest that enhancing incretin signaling with a single-dose injectable GLP-1 RA might be an alternative to dose-titrated basal insulin therapy in patients with T2DM poorly controlled with DPP-4i-based OAD therapy. These findings should be confirmed in a longer and larger trial.Trial RegistrationTrial Registry (UMIN-CTR) as UMIN000012224.Electronic supplementary materialThe online version of this article (10.1007/s13300-018-0486-1) contains supplementary material, which is available to authorized users.

Insulin–glucagon‐like peptide‐1 receptor agonist relay and glucagon‐like peptide‐1 receptor agonist first regimens in individuals with type 2 diabetes: A randomized, open‐label trial study

“…Although this latter outcome might seem somewhat unexpected, the average baseline HbA1c level in the aforementioned participants was low (~8%), and thus, such studies might be insufficient to elucidate the involvement of possible GLP‐1 resistance among those with higher baseline HbA1c values. In the present study, the average baseline FPG and HbA1c values were 228.9 ± 113.9 mg/dL and 10.0% ± 1.8%, respectively, which were much greater than those described in previous research 6 , 7 , 22 , 23 , 24 , 25 . Furthermore, when we stratified participants with baseline HbA1c levels between 7.6% and 16.5%, both therapy regimens significantly reduced the FPG and HbA1c levels by the end of the first and second phases across all HbA1c quartiles.…”

“…In the present study, the initial dosing of degludec was selected according to the doses used in clinical trials 13 , 14 . However, by week 12, the average daily dose was lower than that observed in predominantly Western populations 6 , 7 , 13 , 14 , 22 , but similar to that reported in Japanese populations 24 , 25 . Furthermore, the FPG levels in our Insulin–GLP‐1 RA relay group were congruent with those detected in the investigations using basal insulin 6 , 7 , 22 .…”