Endocrine Abstracts

Introduction: Extended-release (ER) metformin has been available in many countries for the last two decades, and it may have definite advantages vs. conventional (i.e., immediate-release) metformin: Reportedly, it may reduce gastrointestinal adverse effects by about half, thus increasing compliance; moreover, the once-a-day schedule may contribute to increased adherence and persistence, and hopefully improved outcomes. However, ER metformin was unavailable in Spain until 2022: when generic sitagliptin became available, a single-pill combination containing 50 mg sitagliptin and 1000 mg ER metformin was released, while monocomponent ER metformin is still unavailable. We undertook to rechallenge metformin-intolerant T2DM patients treated with a DPP4 inhibitor with the sitagliptin plus ER metformin single-pill combination in order to assess its tolerability and efficacy.

Methods: T2DM patients with HbA1c >7% and GFR (CKD-EPI) >45 mL/min/1.73m², labelled as metformin-intolerant due to gastrointestinal symptoms, and treated with a DPP4 inhibitor (with or without additional hypoglycemic medication) were switched to the 50 mg sitagliptin plus 1000 mg ER metformin single-pill combination, taking 1 pill with the evening meal in the first month and afterwards 2 pills together if the tolerance was good. Additional medication, if any, was unchanged. Data on glycemic control were compared (paired t-test) between the baseline visit and a follow-up visit 3-4 months afterwards. Tolerance data were obtained by questionnaire in the follow-up visit. All patients included gave informed consent. Data are given as mean±sd.

Results: 38 patients were included, 24 (63%) were women, age 55±8 years, diabetes duration 7±3 years. 32 (84%) tolerated 1 pill, although 12 of them (32% of the total) had minor gastrointestinal symptoms which subsided along the first month and did not cause withdrawal. 27 (71%) of the patients tolerated 2 pills, although 7 of them (18% of the total) had minor symptoms after the dose increase. Fasting plasma glucose was reduced from 178±38 mg/dl to 139±26 mg/dl (P< 0.001) in those who tolerated 1 pill, and to 128±19 (P< 0.001) in those who tolerated 2 pills. HbA1c was reduced from 8.2±1.1% to 7.8±0.8% (P=0.058, 1 pill) and 7.6±0.7% (P=0.015, 2 pills). Of 11 patients who did not tolerate the rechallenge, 8 (21%) reported diarrhea, 4 (11%) flatulence, 2 (5%) abdominal pain, 2 (5%) nausea and 1 (3%) dyspepsia.

Conclusions: Rechallenge with ER metformin plus sitagliptin in patients intolerant to conventional metformin was mostly successful, with 5/6 tolerating 1 pill and 7/10 full dose. Side effects were minor, and glycemic control was improved.