Endocrine Abstracts

Introduction and Objective: Metformin is still a mainstay of treatment in patients with type 2 diabetes mellitus (T2DM), but in 10-25% of them there are persistent gastrointestinal disturbances that worsen their quality of life, lead to poor compliance and treatment withdrawal, and ultimately result in worse health outcomes. Extended-Release Metformin (XRM) is much better tolerated, and since 2005 is recommended in the well-respected British NICE guidelines for the treatment of T2DM in patients with gastrointestinal disturbances related to the use of metformin. However in Spain XRM was not available until 2022, after the expiration of the patent of sitagliptin, when a generic combination of XRM/sitagliptin (1000/50 mg) became available, while monocomponent XRM is still not available. We undertook to study whether in patients with T2DM, labeled as metformin-intolerant and treated with a DPP4 inhibitor but insufficiently controlled, the switch from the DPP4 inhibitor to the XRM/sitagliptin combination could improve their glycemic control and renal function.

Design & Method: Patients with T2MD, with HbA1c >7% but <9%; estimated GFR >45 ml/min/1.73 m², labeled as metformin-intolerant and treated with full dose of a DPP4 inhibitor were recruited and, after informed consent, switched to XRM/sitagliptin 100/50 mg beginning with one daily pill, and after one month increasing the dose to 2 daily pills if there were no significant tolerance issues. Fasting glycaemia, HbA1C, estimated GFR (CKD-EPI equation) and albumin/creatinine ratio in a morning urine sample were measured before and 3-4 months after the switch. As albumin/creatinine values are not distributed normally, they are given as median (interquartile range) and compared by Mann-Whitney’s U test

Results: 72 such patients were recruited; 12 did not tolerate the combination, 8 tolerated only one pill, and 52 tolerated both pills. Fasting glucose was reduced from 175±34 to 129±23 mg/dl (P<0.05) with one pill and to 121±21 (P<0.01) with 2 pills. HbA1c was reduced from 8.3±1.0 to 7.7±0.8% (P<0.05) with one pill and to 7.4±0. GFR was unchanged: 57±16 to 59±16 ml/min/1.73 m² 7. Albumin/creatinine quotient was reduced from 39 (17-78) to 29 (14-66) mg/gr (P=0.029). There was a significant positive correlation between albumin/creatinine change and HbA1C change (Spearman’s rho: 0.47, P<0.001).

Conclusions: The switch from DPP4 inhibitor to the XRM-sitagliptin combination was well tolerated in a large majority of the patients, improved significantly the glycemic control and reduced urinary albumin excretion; this reduction seems to be partly driven by the improvement in glycemic control.