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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

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posted on 2022-08-26, 12:14 authored by Kamlesh Khunti, Bernard Charbonnel, Andrew Cooper, Marília B. Gomes, Linong Ji, Paul Leigh, Antonio Nicolucci, Wolfgang Rathmann, Marina V. Shestakova, Afrah Siddiqui, Fengming Tang, Hirotaka Watada, Hungta Chen, DISCOVER investigators

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.

Funding

The DISCOVER study programme is funded by AstraZeneca

History

Citation

Diabetes Obes Metab.2021;1–11.

Author affiliation

Department of Health Sciences

Version

  • VoR (Version of Record)

Published in

Diabetes, Obesity and Metabolism: a journal of pharmacology and therapeutics

Volume

23

Issue

8

Pagination

1823-1833

Publisher

Wiley

issn

1462-8902

eissn

1463-1326

Acceptance date

2021-04-08

Copyright date

2021

Available date

2022-08-26

Spatial coverage

England

Language

eng

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