Exposure to proton pump inhibitors and risk of diabetes: A systematic review and meta-analysis

Table 1 Characteristics of the studies included

Ref.	Country	Study design	Quality	Population	Age in yr	Sex	Comparison	Adjustment	ESs (95%CI)
Ciardullo et al[7], 2022	Italian	Case-control	High	101070	≥ 40	M/F	PPIs vs non-PPIs	Adjusted1	1.56 (1.49, 1.64)
Kuo et al[8], 2022	China	Case-control	High	41880	55.85 ± 13.48	M/F	PPIs vs non-PPIs	Adjusted2	1.34 (1.23, 1.46)
Czarniak et al[6], 2022	Netherlands	Cohort	High	9531	≥ 45	M/F	PPIs vs non-PPIs	Adjusted3	1.49 (1.14, 1.95)
He et al[9], 2021	United Kingdom	Cohort	Moderate	470265	56.34 ± 8.11	M/F	PPIs vs non-PPIs	Adjusted4	1.56 (1.46, 1.66)
Yuan et al[10], 2021	United States	Cohort	High	80500	30-55	F	PPIs vs non-PPIs	Adjusted5	1.22 (1.12, 1.33)
Yuan et al[10], 2021	United States	Cohort	High	95550	25-42	F	PPIs vs non-PPIs	Adjusted5	1.27 (1.17, 1.38)
Yuan et al[10], 2021	United States	Cohort	High	28639	40-75	M	PPIs vs non-PPIs	Adjusted5	1.12 (0.91, 1.38)
Moayyedi et al[12], 2019	Mixed	Randomized controlled trial	High	17598	67.7 ± 8.1	M/F	PPIs vs placebo	Unadjusted	0.96 (0.85, 1.09)
Lin et al[11], 2016	China	Cohort	High	22152	55.38 ± 16.95	M/F	PPIs vs non-PPIs	Adjusted6	0.80 (0.73, 0.88)

¹Adjusted for sex, age, and clinical status.

²Adjusted for age, sex, residence income, indications of proton pump inhibitor (PPI) use, obesity, dyslipidemia, hypertension, and alcohol use disorders.

³Adjusted for age, sex, PPI past use, body mass index (BMI), hypertension, current smoking, alcohol consumption, physical activity, and education levels.

⁴Adjusted for sex, with additional adjustment for diabetes risk factors, including age at recruitment, ethnicity, deprivation, BMI, smoking status, family history of diabetes in a first-degree relative, cardiovascular disease, treated hypertension, corticosteroids use, diagnosis of schizophrenia or bipolar affective disorder, learning disabilities, diagnosis of gestational diabetes, diagnosis of polycystic ovary syndrome, atypical antipsychotics, statins and clinical indications for PPI use.

⁵Adjusted for race, family history of diabetes, BMI, number of pack-years of smoking, alcohol intake per day, physical activity, overall diet quality, total calorie intake, multivitamin use, history of hypertension, hypercholesterolemia, cancer, menopausal status and postmenopausal hormone use in women, number of parity in women, breastfeeding in women, any use of antibiotics, regular non-steroidal anti-inflammatory drug use, any use of steroids, gastroesophageal reflux disease, gastric or duodenal ulcer, upper gastrointestinal tract bleeding, and regular use of H2 receptor agonists.

⁶Adjusted for age, sex, hypertension, gout and/or hyperuricemia, coronary artery disease, stroke, pancreatitis, hyperlipidemia, obesity, H2 blocker use, and clozapine or olanzapine use.

CI: Confidence interval; ESs: Effect quantities; F: Female; M: Male; PPI: Proton pump inhibitor.