Endocrine Abstracts

Introduction and Objectives: Extended-release (ER) metformin may reduce the gastrointestinal adverse effects of conventional metformin, increasing compliance, adherence and persistence. In mid 2022, a single-pill combination (SPC) containing 50 mg sitagliptin plus 1000 mg ER metformin was released in Spain, while monocomponent ER metformin is still unavailable. We rechallenged patients with T2DM labelled as metformin-intolerant and treated with a DPP4i with the mentioned SPC in order to assess its tolerability. With the recent availability (mid 2023) of the cardiovascular risk calculator SCORE2-Diabetes we retrospectively calculated the cardiovascular risk of our patients at baseline and after 3-4 months on treatment with this SPC.

Patients and Methods: Consecutive patients with T2DM patients, HbA1c >7% and GFR (CKD-EPI) >45 mL/min/1.73m² labelled as metformin-intolerant due to gastrointestinal symptoms, and treated with a DPP4i (with or without additional hypoglycemic medication) were switched to the 50 mg sitagliptin plus 1000 mg ER metformin 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 in many patients lifestyle, antihypertensive and cholesterol-lowering medication were adjusted. Tolerance data were obtained by questionnaire in the follow-up visit. Data are given as mean±sd. The calculations were done by intention to treat. All patients included gave informed consent. The SCORE2-Diabetes calculator was obtained at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10361012/bin/appendix_2.xlsx

Results: We calculated the CV risk by SCORE2-Diabetes in 58 patients (39 women, age 53±8 years, 8±3 years since the diagnosis of T2DM), of which 47 tolerated 2 tablets of metformin ER + sitagliptin (1000/50 mg); 6 tolerated 1 tablet and 5 did not tolerate any dose. The baseline CV risk (major event in the next 10 years) was estimated as 12.7±2.2%; 6 patients were classified as intermediate risk, 39 as high risk and 13 as very high risk patients. After 3-4 months of treatment the CV risk was reduced to 10.4±1.9% (P<0.001); 23 patients were classified as intermediate risk, 29 as high risk and 6 as very high risk patients (P<0.001).

Conclusions: A large majority of the patients with T2DM labelled as metformin-intolerant did tolerate the ER metformin plus sitagliptin SPC. Their cardiovascular risk was significantly reduced. The study intervention only added metformin ER as an antidiabetic drug, but in many of the patients there were additional interventions in lifestyle, antihypertensive and cholesterol-lowering drugs. Therefore, the changes in cardiovascular risk must be considered as multifactorial.