Table 1.

Definition of the outcomes of interest

Outcome	Definition
Bone-related conditions	Incident Read code of bone fracture (ankle, foot, toe, hand, finger, hip, femur, humerus, shoulder, clavicle, scapula, lower arm, elbow, wrist, vertebra or unspecific fracture) or osteoporosis.
Hypertension	Incident Read code of hypertension preceded or followed within 180 days prior until 180 days after by a prescription for an antihypertensive drug (ACE inhibitor, ARB, dihydropyridine CCB or thiazide diuretic). The first record of either hypertension or antihypertensive treatment was assigned the date of outcome occurrence.
Peptic ulcer	Incident Read code of peptic ulcer with or without haemorrhage.
Severe infections	Main analysis: incident Read code of an infection preceded or followed within 1 month by a record suggesting hospitalisation or i.v. anti-infective treatment. Sensitivity analysis restricted to patients with IHS linkage (conducted in the nested-case control study only): incident Read code of an infection preceded or followed within 1 month by a hospitalisation whose reason was infection (ICD-10 code of infection in the IHS data).
Herpes zoster	Incident Read code of herpes zoster
DM2	Incident Read code of DM2 and/or a first-time prescription for an oral antidiabetic drug, whichever came first. If a patient was prescribed insulin before any other antidiabetic drug during follow-up (and therefore likely was diagnosed with DM1), the event did not count as an outcome and the person was censored at the date of the insulin prescription.
Cataract	Incident Read code of cataract or a procedure for lens replacement, whichever came first.
Glaucoma	Incident Read code of glaucoma or a first-time prescription for intraocular pressure-lowering therapy, whichever came first.
CKD	Incident Read code of CKD or ≥2 recorded values of an eGFR of < 60 ml/min/1.73m2 within 365 days and separated by ≥90 days (calculated based on the CKD-EPI equation).
Affective disorders	Incident Read code of affective disorders (depression, bipolar affective disorder, manic episodes) preceded or followed within 180 days before or after by a prescription for an antidepressant or mood stabilizing drug, or a Read code indicating psychotherapy. The first record of either affective disorders or the respective treatment was assigned the date of outcome occurrence.
Cardiovascular events	Incident Read code of myocardial infarction, ischaemic heart disease, or ischaemic stroke.

Abbreviations: ACE angiotensin-converting-enzyme, ARB angiotensin II receptor blocker, CCB calcium channel blocker, CKD chronic kidney disease, CKD-EPI Chronic Kidney Disease Epidemiology Collaboration, DM1 diabetes mellitus type 1, DM2 diabetes mellitus type 2, eGFR estimated glomerular filtration rate, IHS integrated hospital episode statistics, i.v. intravenous

Read codes: thesaurus of clinical terms