Flow chart of eligibility.

<p>Flow chart of eligibility.</p

Availability of data within the study period.

<p>Availability of data within the study period.</p

Bias-analysis: Relative rates of types of cancer (recorded in the CPRD)

<p>Abbreviations: CI = confidence interval; CPRD = Clinical Practice Research Datalink; n = number; NJR = National Joint Registry; THR = total hip replacement.</p><p>Rates are number of events per 100 person years. (a) Adjusted for small-area socioeconomic status, smoking status, use of alcohol, body mass index, a history of hypertension, chronic obstructive pulmonary disease (COPD), coronary artery disease (CAD), and a prescribing in the 6 months before of NSAIDs or aspirin, oestrogen containing drugs, oral glucocorticoids, calcium/vitamin D supplements, glucose lowering agents, statins, immunosuppressive agents, bisphosphonates, renin-angiotensin-aldosterone-system (RAAS) inhibitors, platelet inhibitors, beta blockers, calcium channel blockers, diuretics, and organic nitrates.</p

Baseline characteristics of patients with different types of hip replacements and matched controls (NJR cohort).

<p>Abbreviations: BMI = body mass index; COPD = chronic obstructive pulmonary disease; NJR = National Joint Registry; NSAID = non-steroidal anti-inflammatory drug; RAAS = renin-angiotensin-aldosterone-system; SD = standard deviation; THR = total hip replacement.</p

Crude RR of cancer over time in CPRD (and 95% CI) in patients with a metal-on-metal THR compared to patients with another bearing surface THR (as recorded in NJR).

<p>Abbreviations: CI = confidence interval; CPRD = Clinical Practice Research Datalink; NJR = National Joint Registry.</p

Relative rates of types of cancer (as recorded in the CPRD) over time (CPRD cohort).

<p>Abbreviations: CPRD = Clinical Practice Research Datalink; CI = confidence interval; RR = relative rate.</p

Baseline characteristics.

<p>Abbreviations:</p><p>NIAD: non-insulin anti-diabetic drugs;</p><p>SD: standard deviation;</p><p>BMI: body mass index;</p><p>HbA1c: glycated haemoglobin;</p><p>COPD: chronic obstructive pulmonary disease.</p><p>Baseline characteristics.</p

Use of DPP-4 inhibitors and risk of pneumonia in T2DM patients, by cumulative dose and daily dose.

<p>Abbreviations:</p><p>DPP4: dipeptidyl-peptidase-4;</p><p>NIAD: non-insulin anti-diabetic drug;</p><p>IR: incidence rate;</p><p>PY: patient years;</p><p>HR: hazard ratio;</p><p>GLP-1: glucagon-like peptide 1;</p><p>DDD: defined daily dose;</p><p>cum.: cumulative;.</p><p>^a: Numbers do not add up because data on past NIAD user is not shown</p><p>^b: Adjusted for sex, age, smoking status, BMI, alcohol use; a history of lung cancer, COPD, dementia and stroke; use of glucocorticoids, anticonvulsants, proton pump inhibitors, immunosuppressants (excluding glucocorticoids) and antipsychotics in the previous 6 months, influenza vaccination in the previous year, pneumococcal vaccination in the previous 5 years, <i>Haemophilus influenza</i> vaccination ever before, past use of NIADs and the most recently recorded HbA1c level in the previous year</p><p>^c: Current use: a DPP4I-prescription ≤2 months before, recent use: a DPP4I-prescription 3–8 months before; past use: a DPP4I-prescription >8 months before.</p><p>Use of DPP-4 inhibitors and risk of pneumonia in T2DM patients, by cumulative dose and daily dose.</p

Use of DPP-4 inhibitors and risk of pneumonia in T2DM patients, by sex and age.

<p>Abbreviations:</p><p>NIAD: non-insulin anti-diabetic drug;</p><p>IR: incidence rate;</p><p>HR: hazard ratio;</p><p>DPP4: dipeptidyl-peptidase-4;</p><p>GLP-1: glucagon-like peptide 1</p><p>^a: Numbers do not add up because data on past NIAD use, current GLP1 agonist and recent/past DPP4I is not shown</p><p>^b: Adjusted for sex, age, smoking status, BMI, alcohol use; a history of lung cancer, COPD, dementia and stroke; use of glucocorticoids, anticonvulsants, proton pump inhibitors, immunosuppressants (excluding glucocorticoids) and antipsychotics in the previous 6 months, influenza vaccination in the previous year, pneumococcal vaccination in the previous 5 years, <i>Haemophilus influenza</i> vaccination ever before, past use of NIADs, use of GLP1 analogues, recent and past use of DPP4Is (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0139367#pone.0139367.t002" target="_blank">Table 2</a>, footnote b) and the most recently recorded HbA1c level in the previous year</p><p>^c: Current use: a DPP4I-prescription ≤2 months before.</p><p>Use of DPP-4 inhibitors and risk of pneumonia in T2DM patients, by sex and age.</p

Baseline characteristics of statin users and non-statin users.

<p>Baseline characteristics of statin users and non-statin users.</p