Associations between second‐line glucose‐lowering combination therapies with metformin and HbA1c, body weight, quality of life, hypoglycaemic events and glucose‐lowering treatment intensification: The DISCOVER study

Aim:To explore the effects of second-line combination therapies with metformin onbody weight, HbA1c and health-related quality of life, as well as the risks ofhypoglycaemia and further treatment intensification in the DISCOVER study, a 3-year,prospective, global observational study ofpatients with type 2 diabetes initiating sec-ond-line glucose-lowering therapy.Materials and Methods:Adjusted changes from baseline in weight, HbA1c and36-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 hypoglycaemiaand further intensification were assessed using interval censored analyses.Results:At baseline, 7613 patients received metformin in combination with asulphonylurea (SU; 40.9%), a dipeptidyl peptidase-4 (DPP-4) inhibitor (48.3%), asodium-glucose co-transporter-2 (SGLT-2) inhibitor (8.3%) or a glucagon-likepeptide-1 (GLP-1) receptor agonist (2.4%). After 36 months, all combinations showedsimilar reductions in HbA1c (0.8%-1.0%), however, metformin plus a DPP-4 inhibitor,an SGLT-2 inhibitor or a GLP-1 receptor agonist was associated with greater weightloss (1.9, 2.9 and 5.0 kg, respectively) than metformin plus an SU (1.3 kg,P< .0001).Proportions of further treatment intensification were similar across combinations(19.9%-26.2%). Patients prescribed metformin plus an SU more often reported oneor more hypoglycaemic events (11.9%) than other combinations (3.9%-6.4%,P< .0001). SF-36v2 summary scores were typically lowest among patients prescribedmetformin and an SU.Conclusions:Combinations of metformin with an SU were associated with the low-est weight reduction, highest risk of hypoglycaemia and lower SF-36v2 scores.