Endocrine Abstracts

Introduction and Objective: Extended-release metformin has much better gastrointestinal tolerability than conventional (immediate release)metformin and according to the UK NICE guidelines should be offered to patients who have gastrointestinal tolerance issues with conventional metformin. We rechallenged patients with T2DM labelled as metformin-intolerant and treated with a DPP4i with a single-pill combination (SPC) of extended release metformin and sitagliptin (1000/50 mg) in order to assess its tolerability. We retrospectively calculated the cardiovascular risk of our patients at baseline and after 3-4 months on treatment with this SPC with the SCORE2-Diabetes calculator, and assessed the changes in office blood pressure.

Design & Methods: Consecutive patients with T2DM, HbA1c >7% but < 9% and eGFR (CKD-EPI) >45 ml/min/1.73m² labelled as metformin-intolerant due to gastrointestinal symptoms, and treated with a DPP4i were switched to the mentioned SPC, taking 1 pill daily in the first month and afterwards 2 pills if the tolerance was good. Additional antidiabetic medication, if any, was unchanged; however, lifestyle, antihypertensive and cholesterol-lowering medication were adjusted according to current guidelines. Tolerance data were obtained by questionnaire in the follow-up visit. Calculations were done by intention to treat.

Results: We applied the SCORE2-Diabetes in 72 patients (45 women, aged 55±8 years, 7.5±3.2 years since the diagnosis of T2DM), of which 52 tolerated 2 tablets, 8 tolerated 1 tablet and 12 did not tolerate any. After 3-4 months of treatment, systolic office blood pressure was reduced from 147.3±21.2 to 131.8±18.9 mmHg (P<0.001); diastolic office blood pressure was reduced from 92.8±16.3 to 81.8±15.7 mmHg (P<0.001). The number of patients at target (<130/80 mmHg) changed from 14 (19.1%) to 33 (48.5%), P=0.0011 The baseline CV risk (major event in the next 10 years) was estimated as 12.8±2.3%; 7 (10.3%) patients were classified as intermediate risk, 46 (67.6%) as high risk and 15 (22.1%) as very high risk patients. After 3-4 months of treatment the 10-year CV risk was reduced to 10.3±1.8% (P<0.001); 27 (39.7%) patients were classified as intermediate risk, 34 (50%) as high risk and 7 (10.3%) as very high risk patients (P<0.001).

Conclusions: A large majority of the patients tolerated the rechallenge; their blood pressure and cardiovascular risk were significantly reduced. These changes must be considered as multifactorial, as in most patients there were additional interventions in lifestyle, antihypertensive and cholesterol-lowering drugs.