Associations between second-line glucose-lowering combination therapies with metformin and HbA 1c , body weight, quality of life, hypoglycaemic events, and glucose-lowering treatment intensification: the DISCOVER study.

AIMS: Using data from DISCOVER, a 3-year, prospective, global observational study of patients with type 2 diabetes initiating second-line glucose-lowering therapy, we sought to explore the effects of second-line dual combinations therapies plus metformin on body weight, glycated haemoglobin (HbA1c ), health-related quality of life, and risks of hypoglycaemia and further treatment intensification. MATERIALS AND METHODS: Adjusted changes from baseline in weight, HbA1c , and 36-item Short Form Health Survey version 2 (SF-36v2) summary scores at 6, 12, 24, and 36 months were assessed using linear mixed models. Risk of hypoglycaemia and further intensification were assessed using interval censored analyses. RESULTS: At baseline, 7613 patients received metformin in combination with a sulphonylurea (SU; 40.9%), a dipeptidyl peptidase-4 (DPP-4) inhibitor (48.3%), a sodium-glucose co-transporter 2 (SGLT-2) inhibitor (8.3%), or a glucagon-like peptide-1 (GLP-1) receptor agonist (2.4%). After 36 months, all combinations showed similar reductions in HbA1c (0.8-|1.0%), however, metformin plus a DPP-4 inhibitor, an SGLT-2 inhibitor, or a GLP-1 receptor agonist were associated with greater weight loss (1.9, 2.9, and 5.0 kg, respectively) than metformin plus an SU (1.3 kg, P < 0.0001). Proportions of further treatment intensification were similar across combinations (19.9-26.2%). Patients prescribed metformin plus an SU more often reported one or more hypoglycaemic events (11.9%) than other combinations (3.9-|6.4%, P < 0.0001). SF-36v2 summary scores were typically lowest among patients prescribed metformin and an SU. CONCLUSIONS: Combinations of metformin with an SU were associated with the lowest weight reduction, highest risk of hypoglycaemia, and lower SF-36v2 scores. This article is protected by copyright. All rights reserved.