Endocrine Abstracts

Introduction and Objectives: The tolerance of extended-release metformin (XRM) is superior to that of conventional metformin. XRM is recently available in Spain as a fixed combination with sitagliptin, but not in monotherapy. There are no data yet on how additional antidiabetic treatment can modify the effects of the XRM/sitagliptin combination. After assessing the efficacy and tolerability of XRM/sitagliptin in patients with T2DM labelled as metformin-intolerant and treated with a DPP4 inhibitor (DPP4i), we performed additional analyses in order to assess if additional treatment could modify these results.

Patients and Methods: Consecutive patients with T2DM, HbA1c >7% and GFR (CKD-EPI) >45 mL/min/1.73m² labelled as metformin-intolerant due to gastrointestinal symptoms, and treated with a DPP4i were switched to the 50 mg sitagliptin plus 1000 mg XRM combination, taking 1 pill daily in the first month and afterwards 2 pills if the tolerance was good. Tolerance data were obtained by questionnaire in the follow-up visit. All Included patients granted informed consent.

Results: 29 patients previously treated with SGLT2i (17 with empagliflozin, 8 with dapagliflozin and 4 with canagliflozin) could be pooled and analyzed vs. 43 not treated with any SGLT2i. No patient was treated with metformin (due to assumed intolerance); all were treated with DPP4i (by protocol) but none with a GLP-1ra (due to incompatibility with iDPP4); 5 patients were treated with insulin, 4 with gliclazide, 3 with repaglinide and 3 with pioglitazone; these drugs were unsuitable for analysis due to sample size. There were no significant differences for the reductions in fasting glycemia (without SGLT2i: 36±16 mg/dl with 1 pill, 45±17 mg/dl with 2 pills; with SGLT2i 32±16 mg/dl with 1 pill, 40±13 mg/dl with 2 pills) or in HbA1c (without SGLT2i: 0.64±0.30% with 1 pill, 0.95±0.32% with 2 pills; with SGLT2i 0.59±0.28% mg/dl with 1 pill, 0.91±0.30% with 2 pills) induced by the switch from DPP4i to XRM/sitagliptin in patients with vs. without previous SGLT2i treatment. There were also no significant differences for tolerance: without SGLT2i: 8 patients (18.6%) did not tolerate the rechallenge, and 5 (11.6%) tolerated only 1 pill; with SGLT2i, 4 (13.8%) did not tolerate, and 3 (10.3%) tolerated only 1 pill.

Conclusions: A large majority of the patients with T2DM labelled as metformin-intolerant and treated with DPP4i tolerated XRM/sitagliptin, and their fasting blood glucose and HbA1c significantly improved. The concomitant use of iSGLT2i did not modify these results. Other antidiabetic treatments could not be meaningfully analyzed.