Endocrine Abstracts

Introduction and Objectives: Since 2005, the NICE guidelines on T2DM recommend extended-release metformin (XRM) in patients with gastrointestinal disturbances induced by conventional metformin, as the tolerance of XRM is clearly superior, improving patient compliance, satisfaction and outcomes. In Spain XRM is recently available, but only in a fixed combination with sitagliptin. As yet, data on the efficacy, tolerability and impact on lipid profile of this combination are not available. We undertook to study if treatment with XRM/sitagliptin can improve the lipid profile in patients with T2DM previously labeled as metformin-intolerant and treated with a DPP4 inhibitor (DPP4i)

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 (with or without additional antidiabetic medication) 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. Additional antidiabetic medication, if any, was unchanged; however, the patients received lifestyle advice, and antihypertensive and cholesterol-lowering medications were adjusted according to current ESC-ESH-EAS recommendations. Tolerability data were obtained by questionnaire in the follow-up visit. Data are given as mean±sd. The calculations were done by intention-to-treat. Comparisons were made by the paired t-test. All Included patients granted informed consent.

Results: Changes in lipid profile were studied in 70 patients (45 women, age 54±8 years, with 7.8±3.0 years since the diagnosis of T2DM), of which 51 (73%) tolerated 2 tablets of XRM/sitagliptin (1000/50 mg); 8 (11%) tolerated 1 tablet and 11 (16%) did not tolerate any. The reductions in fasting plasma glucose were 36 mg/dl with 1 pill and 44 mg/dl with 2 pills, and in HbA1c were 0.6% with 1 pill and 0.9% with 2 pills (all P<0.01). After 3-4 months of treatment, total cholesterol was reduced from 217±33 to 197±31 mg/dl (P<0.001); triglycerides from 190±48 to 158±46 mg/dl (P<0.01); LDL-cholesterol from 130±29 to 108±26 mg/dl (P<0.001), and HDL-cholesterol rose from 50 ± 15 to 57 ± 16 mg/dl (P<0.01).

Conclusion: A large majority of the patients with T2DM labelled as metformin-intolerant did tolerate XRM/sitagliptin, and their lipid profile significantly improved. The study intervention only added XRM 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 the lipid profile must be considered as multifactorial.