Association between SGLT2 inhibitor treatment and diabetic ketoacidosis and mortality in people with type 2 diabetes admitted to hospital with COVID-19

   Objective  To determine the association between prescription of SGLT2 inhibitors and diabetic ketoacidosis (DKA) incidence or mortality in people with type 2 diabetes hospitalized with COVID-19.  Research Design and Methods  This was a retrospective cohort study based on secondary analysis of data from a large nationwide audit from a network of 40 centres in United Kingdom with data collection up to December 2020 that was originally designed to describe risk factors associated with adverse outcomes among people with diabetes who were admitted to hospital with COVID-19.. The primary outcome for this analysis was DKA on or during hospital admission. The secondary outcome was mortality. Crude, age-sex adjusted and multivariable logistic regression models, were used to generate odds ratios and 95% confidence intervals for people prescribed SGLT2 inhibitor compared to those not prescribed SGLT2 inhibitor.   Results  The original national audit included 3067 people with type 2 diabetes who were admitted to hospital with COVID-19, of whom 230 (7.5%) were prescribed SGLT2 inhibitors prior to hospital admission. Mean (SD) age of the overall cohort was 72 years, 62.3% were men and 34.9% were prescribed insulin. Overall, 2.8% of the total population had DKA and 35.6% people died. The adjusted odds of DKA were not significantly different between those prescribed SGLT2 inhibitors and those not (OR 0.56, 0.16-1.97). The adjusted odds of mortality associated with SGLT2 inhibitors were similar in the total study population (OR 1.13, 0.78-1.63 ), in the sub-group prescribed insulin (OR 1.02, 0.59-1.77), and in the sub-group that developed DKA (OR 0.21, 0.01-8.76).  Conclusions We demonstrate a low risk of DKA and high mortality rate in people with type 2 diabetes admitted to hospital with COVID-19 and limited power but no evidence of increased risk of DKA or in-hospital mortality associated with prescription of SGLT2 inhibitors. </p

Distribution of visual acuity by various demographic factors.

<p>Distribution of visual acuity by various demographic factors.</p

Characteristics of the study population.

<p>Characteristics of the study population.</p

Logistic regression analysis for each of the visual impairment categories.

<p>Vision in better eye; Adjusted for all other factors in the table.</p

Logistic regression analyses.

*<p>Adjusted for all factors on the table.</p><p>CSMO- clinically significant macular oedema; R1- Mild to moderate non-proliferative diabetic retinopathy; R2- Severe non-proliferative diabetic retinopathy; R3- Proliferative diabetic retinopathy; M1P1- laser treated diabetic maculopathy; STDR-sight threatening diabetic retinopathy.</p

Prevalence of diabetic retinopathy in people with type 2 diabetes.

a<p>Standardised to the age-structure of the Caucasian population;</p><p>Number (missing data on age): White Europeans n = 30,350 (20) African/Afro-Caribbean n = 8,023 (0) South Asian n = 3,397 (8).</p><p>CSMO- clinically significant macular oedema; M1- maculopathy P1- macular laser; STDR- sight threatening diabetic retinopathy; R1- mild to moderate non-proliferative diabetic retinopathy; R2- pre-proliferative diabetic retinopathy; R3- Proliferative diabetic retinopathy.</p

Prevalence of retinopathy in people with type 1 diabetes.

a<p>Standardised to the age-structure of the white European population;</p><p>Number (missing data on age): White Europeans n = 2,628 (0) African/Afro-Caribbean n = 344 (1), South Asian n = 120 (0).</p><p>CSMO- clinically significant macular oedema; M1- maculopathy P1- macular laser; STDR- sight threatening diabetic retinopathy; R1- mild to moderate non-proliferative diabetic retinopathy; R2- pre-proliferative diabetic retinopathy; R3- Proliferative diabetic retinopathy</p

Disease grading protocol in National Guidelines on Screening for Diabetic retinopathy grading in England and Wales screening programmes.

9<p>International classification proposed by American Academy of Ophthalmologists.</p

Characteristics of the study population.

<p>Characteristics of the study population.</p

Prevalence of visual impairment in people with diabetes.

*<p>Vision in the better eye. Study cut-points (<6/9, <6/12 and <6/60) given as well as cut-points for comparison purposes (<6/18 WHO visual impairment and < = 6/60 NSC criteria).</p>**<p>Standardised to the age-structure of the Caucasian population.</p>***<p>In this dataset: <6/12 was the same numerically as < = 6/18 (NSC criteria).</p><p>White European n = 32,989 African/Afro-Caribbean n = 8375, South Asian n = 3510.</p