The use of sodium-glucose co-transporter-2 inhibitors or glucagon-like peptide-1 receptor agonists versus sulfonylureas and the risk of lower limb amputations: a nation-wide cohort study

Table 4 Risk of LLA in current SGLT2-I use compared to current SU use, stratified by cumulative dose and continuous duration of use

	Number of LLAs (N = 564)	IR (/1000 PY	Age/sex adjusted HR (95%CI)	Fully adjusted HR (95%CI)^a
Current SU use	54	2.14	Reference
Current SGLT2-I use	36	2.30	1.24 (0.81–1.91)	1.10 (0.71–1.70)
By cumulative dose
< 250 DDDs	15	2.28	1.26 (0.71–2.24)	1.15 (0.64–2.05)
250–1200 DDDs	10	1.46	0.79 (0.40–1.55)	0.68 (0.34–1.34)
≥ 1200 DDDs	11	4.92	2.58 (1.34–5.00)	2.24 (1.16–4.36)
By continuous duration of use
1–160 days	15	2.42	1.32 (0.74–2.36)	1.20 (0.67–2.15)
161–365 days	7	1.68	0.91 (0.41–2.01)	0.83 (0.37–1.83)
> 365 days	14	3.18	1.68 (0.92–3.04)	1.38 (0.76–2.52)

The models have also been adjusted for current DPP4-I use (149 LLAs), current combined use (90 LLAs), current other NIGLD use (59 LLAs), current GLP1-RA use (55 LLAs), and past NIGLD use (121 LLAs) (not shown)
LLA lower limb amputation, IR incidence rate, PY person years, HR hazard ratio, CI confidence interval, NIGLD non-insulin glucose lowering drug, SU sulfonylurea, DPP4-I dipeptidyl peptidase-4 inhibitor, SGLT2-I sodium-glucose co-transporter-2 inhibitor, DDD daily defined dose
^aAdjusted for age; sex; diabetes duration; income category; history of diabetic foot ulcer, neuropathy, atherosclerosis, osteomyelitis, retinopathy, hypertension, heart failure, ischaemic heart disease, or peripheral arterial disease; and the use of antithrombotic agents, lipid lowering drugs, potassium sparing diuretics, beta blockers, or angiotensin receptor blockers in the 6 months before the start of the exposure interval

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