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0 0.5 1 1.5 2+ Mortality 23% Improvement Relative Risk Metformin for COVID-19  Khunti et al.  Prophylaxis Is prophylaxis with metformin beneficial for COVID-19? Retrospective 2,851,465 patients in the United Kingdom Lower mortality with metformin (p<0.000001) Khunti et al., The Lacent Diabetes & E.., Mar 2021 Favors metformin Favors control

Prescription of glucose-lowering therapies and risk of COVID-19 mortality in people with type 2 diabetes: a nationwide observational study in England

Khunti et al., The Lacent Diabetes & Endocrinology, doi:10.1016/S2213-8587(21)00050-4
Mar 2021  
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Metformin for COVID-19
3rd treatment shown to reduce risk in July 2020
*, now known with p < 0.00000000001 from 88 studies.
No treatment is 100% effective. Protocols combine complementary and synergistic treatments. * >10% efficacy in meta analysis with ≥3 clinical studies.
4,100+ studies for 60+ treatments.
Retrospective 2,851,465 people with type 2 diabetes in the UK, showing lower mortality with existing metformin use. Results are subject to confounding by indication because metformin is typically used early in the progression of type 2 diabetes.
risk of death, 23.0% lower, HR 0.77, p < 0.001, adjusted per study.
Effect extraction follows pre-specified rules prioritizing more serious outcomes. Submit updates
Khunti et al., 30 Mar 2021, retrospective, population-based cohort, United Kingdom, peer-reviewed, 15 authors.
This PaperMetforminAll
Prescription of glucose-lowering therapies and risk of COVID-19 mortality in people with type 2 diabetes: a nationwide observational study in England
Prof Kamlesh Khunti, Peter Knighton, Francesco Zaccardi, Chirag Bakhai, Emma Barron, Naomi Holman, Partha Kar
Background In patients with type 2 diabetes, hyperglycaemia is an independent risk factor for COVID-19-related mortality. Associations between pre-infection prescription for glucose-lowering drugs and COVID-19-related mortality in people with type 2 diabetes have been postulated but only investigated in small studies and limited to a few agents. We investigated whether there are associations between prescription of different classes of glucose-lowering drugs and risk of COVID-19-related mortality in people with type 2 diabetes. Methods This was a nationwide observational cohort study done with data from the National Diabetes Audit for people with type 2 diabetes and registered with a general practice in England since 2003. Cox regression was used to estimate the hazard ratio (HR) of COVID-19-related mortality in people prescribed each class of glucose-lowering drug, with covariate adjustment with a propensity score to address confounding by demographic, socioeconomic, and clinical factors. Findings Among the 2 851 465 people with type 2 diabetes included in our analyses, 13 479 (0•5%) COVID-19-related deaths occurred during the study period (Feb 16 to Aug 31, 2020), corresponding to a rate of 8•9 per 1000 person-years (95% CI 8•7-9•0). The adjusted HR associated with recorded versus no recorded prescription was 0•77 (95% CI 0•73-0•81) for metformin and 1•42 (1•35-1•49) for insulin. Adjusted HRs for prescription of other individual classes of glucose-lowering treatment were as follows: 0•75 (0•48-1•17) for meglitinides, 0•82 (0•74-0•91) for SGLT2 inhibitors, 0•94 (0•82-1•07) for thiazolidinediones, 0•94 (0•89-0•99) for sulfonylureas, 0•94 (0•83-1•07) for GLP-1 receptor agonists, 1•07 (1•01-1•13) for DPP-4 inhibitors, and 1•26 (0•76-2•09) for α-glucosidase inhibitors. Interpretation Our results provide evidence of associations between prescription of some glucose-lowering drugs and COVID-19-related mortality, although the differences in risk are small and these findings are likely to be due to confounding by indication, in view of the use of different drug classes at different stages of type 2 diabetes disease progression. In the context of the COVID-19 pandemic, there is no clear indication to change prescribing of glucoselowering drugs in people with type 2 diabetes.
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